1.) Anitua E, Sanchez M, Nurden AT, Zalduendo MM, de La Fuente M, Azofra J, Andia I. Platelet
Released Growth Factors Ehnace the Secretion of Hyaluronic Acid and Induce Hepatocyte
Growth factor in Ostoarthritic Patients. Rheumatology. 2007 Dec. 46(12)
PRP increases hyaluronic acid production by synovial cells but does not halt the effects of IL-
1beta(+)
2.) Baboldashti NZ,*1"* MSc, Raewyn C. Poulsen,* PhD, Sarah L. Franklin,* PhD,
Mark S. Thompson,1"* MEng, PhD, and Philippa A. Hulley,* PhD. Platelet-Rich Plasma Protects
Tenocytes From Adverse Side Effects of Dexamethasone and Ciprofloxacin. American Journal of
Sports Medicine, Vol. 39, No. 9
Ciprofloxacin can cause tenocyte cell death, dexamethasone can cause tenocyte senescence-
PRP protects(+)
3.) Baltzer AWA M.D.f, C. Moser M.D.f, S. A. Jansen M.D.§ and R. Krauspe M.D4. Autologous conditioned serum (Orthokine) is an effective treatment for knee Osteoarthritis. Osteoarthritis
and Cartilage (2009) 17,152-160
Autologous conditioned serum (ACS) was developed in the mid-1990s in an attempt to generate an injectable material enriched in endogenous IL-1 Ra as a novel therapeutic for OA. Meijer et a/.27 noted that exposure of bloodto glass beads elicits a vigorous, rapid increase in the synthesis of several anti-inflammatory cytokines, includingll_-1Ra.
This observation is the basis for producing ACS, which is injected into the affected joint in a series of six intra-articular injections given twice a week for 3 Weeks-, 2 year followup(+)
4.) Barber AF, M.D., Scott A. Harnack, M.D., Stephen J. Snyder, M.D., and Onur Hapa, M.D. Rotator
Cuff Repair Healing Influenced by Platelet-Rich Plasma Construct Augmentation. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 27, No 8 (August), 2011: pp 1029-1035
Lower re-tear rates(+)
5.) Beck J, Evans D, Tonino P, Yong S, Callaci JJ. The Biomechanical and Histologic Effects of Platelet-
Rich Plasma on Rat Rotator Cuff Repairs. Am J Sports Med. Vol. 40 No. 9, 2012
Notes non PRP groups had higher failure strain at 7 days, PRP higher at 21 days, PRP had higher fibroblastic response and vascular response at each time and PRP had more linear aligned fibers at 21 days(+), aids in being cautious for the first 3 weeks with post-op therapy(+)
6.) Bergeson AG,* MD, Robert Z. Tashjian,*1" MD, Patrick E, Greis,* MD,Julia Crim;* MD, Gregory J.
Stoddard,* MPH, and Robert T. Burks,** MD. Effects of Platelet-Rich Fibrin Matrix on Repair
Integrity of At-Risk Rotator Cuff Tears. American Journal of Sports Medicine, Vol. 40, No. 2
PRFM(Cascade) did not help re-tear rates and did not increase functional outcome(-)

7.) Carofino B, M.D., David M. Chowaniec, B.S., Mary Beth McCarthy, B.S.,James P. Bradley, M.D.,
Steve Delaronde, M.P.H., M.S.W., Knut Beitzel, M.D.,Mark P. Cote, P.T., D.P.T., Robert A. Arciero,
M.D., and Augustus D. Mazzocca, M.S., M.D. Corticosteroids and Local Anesthetics Decrease
Positive Effects of Platelet-Rich Plasma: An In Vitro Study on HumanTendon Cells. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 28, No 5 (May), 2012: pp 711-719 local anesthetics and steroids decrease cell proliferation and viability of tenocytes with prp(neutral)
8.) Castillo TN,* Michael A. Pouliot,* MD, Hyeon Joo Kim,* PhD, and Jason L. Dragee,*1" MD.
Comparison of Growth Factor and Platelet Concentration From Commercial Platelet-Rich Plasma
Separation Systems. American Journal of Sports Medicine, Vol. 39, No. 2
Various systems make various concentration(neutral)
9.) Castricini R,* MD, Umile Giuseppe Longo,1" MD, MSc, Massimo De Benedetto,* MD,Nicola
Panfoli,* MD, Piergiorgio Pirani,* MD, Raul Zini,* MD,Nicola Maffulli,§11 MD, MS, PhD,
FRCS(Orth), and Vincenzo Denaro,1 MD. Platelet-Rich Plasma Augmentation for Arthroscopic
Rotator Cuff Repair. e American Journal of Sports Medicine, Vol. 39, No. 2
PRFM did not improve healing of rotator cuff repair(-)
10.) de Almeida AM, MD, MS, Marco Kawamura Demange, MD, PhD,Marcel Faraco Sobrado,
Marcelo Bordalo Rodrigues, MD, Andre Pedrinelli MD, PhD, and Arnaldo Jose Hernandez MD,
PhD. Patellar Tendon Healing With Platelet-Rich Plasma. American Journal of Sports Medicine,
Vol. 40, No, 6
PRP, 7x baseline, showed decreased pain, better healing of patellar ligament donor site for
ACL(+)
11.) de Jonge S,*1"* MD, Robert J. de Vos,* MD, PhD, Adam Weir,* MD, Hans T. M. van Schie,t§
DVM, PhD, Sita M. A. Bierma-Zeinstra^11 PhD, Jan A. N. Verhaar,1" MD, PhD, Harrie
Weinans,1"11 PhD, and Johannes L Tol,* MD, PhD. One-Year Follow-up of Platelet-Rich Plasma
Treatment in Chronic Achilles Tendinopathy. American Journal of Sports Medicine, Vol. 39, No.
Biomet PRP, no difference in outcomes and ultrasonography_subjective(-)
12.) DeLong MJ, B.Sc., Ryan P. Russell, M.A., and Augustus D. Mazzocca, M.S., M.D. Platelet-Rich
Plasma: The PAW Classification System. Arthroscopy: The Journal of Arthroscopic and Related
Surgery, Vol 28, No 7 (July), 2012: pp 99S-I009
Classification includes platelet numbers, activation and white blood cell count(Neutral)
13.) Dragoo JL,*1" MD, Hillary J. Braun. Comparison of the Acute Inflammatory ! Response of Two
Commercial Platelet-Rich Plasma Systems in Healthy Rabbit Tendons. The American Journal of
Sports Medicine, Vol. 40, No.
5 days after injections L-PRP more inflammation than Cascade, at 14 days the same(-/+)
14.) Ehrenfest DMD, Lars Rasmusson and Tomas Albrektsson. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRP). Trends in
Biotechnology Vol.27 No.3, 2009
Classification System of PRP(neutral)

15.) Fallouh L, MD, PhD, Koichi Nakagawa, MD, PhD, Takahisa Sasho, MD, PhD, Momoko Aral, ME,
Sota Kitahara, MD, PhD, Yuichi Wada, MD, PhD, Hideshige Moriya, MD, PhD, Kazuhisa
Takahashi, MD, PhD. Effects of Autologous Platelet-Rich Plasma on Cell Viability and Collagen
Synthesis in Injured Human Anterior Cruciate Ligament. J Bone Joint Surg Am. 2010;92:2909-16
PRP enhanced cell viability , number and ACL extracellular collagen(+)
16.) Filardo G, Kon E. Platelet Rich Plasma Injections for Degenerative Cartilage lesions and
Osteoarthritis.Knee Surg Sports Traumatology, 2011 19:528-535
PRP effective in alleviating symptoms up to 24 months, fell off around 9-12 months(+)
17.) Foster TE, *f MD, Brian L Puskas,1" MD, Bert R. Mandelbaum,* MD, Michael B. Gerhardt,* MD, and Scott A, Rodeo,§ MD. Platelet-Rich Plasma From Basic Science to Clinical Applications.
American Journal of Sports Medicine, Vol. 37, No. 11, 2009
Review- initially anti-doping agencies against but now have switched(+)
18.) Fratalocchi F, PHT, Alessandra Milani, MS, and Franco Postacchini,
Hyunchul Jo C,*1" MD, Ji Eun Kim,1" MS, Kang Sup Yoon,1 MD, and Sue Shin,* MD. Platelet-
Rich Plasma Stimulates Cell Proliferation and Enhances Matrix Gene Expression and
Synthesis in Tenocytes From Human Rotator Cuff Tendons With Degenerative Tears.
American Journal of Sports Medicine, Vol. 40, No. 5
PRP stimulated tenocyte cell proliferation and production of tendon extracellular matrix(+)
19.) Getgood A, Henson F, Skelton C, herrara E, Brooks R, Fortier L, Rushton N. The Augmentation of a Collagen/Glycosaminoglycan Biphasic Osteochondral Scaffold with Platelet-Rich Plasma and
Concentrated Bone Marrow Aspirate for Osteochondral Defect Repair in Sheep. Cartilage 3(4),
2012 351-363
PRP creates better hyaline-like cartilage than controls, PRP/BMAC better hyaline-like cartilage than controls and less subchondral bone cyst formation(+)
20.) Gosens T,*"1" MD, PhD, Joost C. Peerbooms,* MD, Wilbert van Laar,* and Brenda L, den
Oudsten,1". Ongoing Positive Effect of Platelet-Rich Plasma Versus Corticosteroid Injection in
Lateral Epicondylitis. American Journal of Sports Medicine, Vol. 39, No. 6, 2011
PRP better than cortisone even at 2 years(+)
21.) Gumrna S, MD, PhD, Vincenzo Campagna, MD, Giancarlo Ferrazza, MD, Giuseppe Giannicola,
MD. Use of Platelet-Leukocyte Membrane in Arthroscopic.Repair of Large Rotator Cuff Tears. J
BoneJointSurgAm. 2D12;94:1345
PRP improves repair integrity(+)
22.) Harrison S,* Patrick Vavken,* MD, Sherwin Kevy,f MD, May Jacobson,* PhD, David Zurakowski,*
PhD, and Martha M, Murray,** MD. Platelet Activation by Collagen Provides Sustained Release of Anabolic Cytokines. AJSM, 2011
Collagen sustains a release, thrombin immediate(neutral)
23.) Kisiday JD, C., Wayne Mcllwraith, William G. Rodkey, David D. Frisbie, J.Richard Steadman.
Effects of Platelet-Rich Plasma Composition on Anabolic and Catabolic Activities inEquine
Cartilage and Meniscal Explants. Cartilage.3(3) 245-254

Suggests that Leukocytes may not be good for joints- IL-1beta its effect? Not solid study-in vitro(?)
24.) Majewski,*1" MD, Peter E. Ochsner,* MD, Fanjun Liu,§ PhD, Rudolf Fluckiger,§ PhD, and Christopher H. Evans,§ PhD. Accelerated Healing of the Rat Achilles
Tendon in Response to Autologous
Conditioned Serum AM J Sports Med, Vol. 37 No. 11, 2009
ACS makes tendon stronger(+)
25.) Mazzocca AD,*f MS, MD, Mary Beth R. McCarthy,1" BS, David M. Chowaniec,f Evan M. Dugdale,f
Derek Hansen,1" MD, Mark P. Cote,1 DPT, James P. Bradley,* MD,Anthony A. Romeo,§ MD,
Robert A. Arciero,1" MD, and Knut Beitzel,1" MA, MD. The Positive Effects of DifferentPlatelet-
Rich Plasma Methods onHuman Muscle, Bone, and Tendon Cells. American Journal of Sports
Medicine, Vol. 40, No. 8
Various PRP concentration can affect different cell targets
Osteoblasts. Proliferation was significantly increased by addition of PK.PLP compared with all controls (FBS low, FBS high,
Blood) (P < .05) (Figure 1). Addition of PRPDSto osteoblasts led to significantly increased proliferation compared with all controls, native blood, and PRPfjp (P <.05). Proliferation was less when PRPjp was compared with PRPLp but did not reach statistical significance (P >.05). PRPHP showed significantly less proliferation compared with PRPDs CP < -05).
Myocytes. Proliferation was significantly increased by addition of PR?LP compared with, native blood (P !< .05)(Figure 2). Adding
PRPos or PRPHp to myocytes showedno significant increase in proliferation compared with the controls or the other separations.
Tenocytes. Proliferation was significantly increased by addition of PR?LP compared with all controls (FBS low,FBS high, Blood) (P <
.05) (Figure 3). There was no differencein the proliferation of tenocytes comparing all 3 PRP types. Addition of PRPDs showed a significant increase compared with the controls and native blood. For tenocytes, there was a significant increase (P < .05) seen when
PRPHp was added compared with the controls and native "blood but not compared with the other separations(+)
26.) Mazzocca AD, MS, MD, Mary Beth R. McCarthy, BS, David M. Chowaniec, BS, Mark P. Cote, DPT,
Anthony A. Romeo, MD, James P. Bradley, MD, Robert A. Arciero, MD, and Knut Beitzel, MD.
Platelet-Rich Plasma Differs According to Preparation Method and Human Variability. J Bone
Joint Surg Am. 2012; 94:308-16
Preparation methods varied with content and multiple samples from same patient showed significant variability(neutral)
27.) McCarrel T, Minas T, Fortier L. Optimization of Leukocyte Concentration in Platelet-Rich Plasma for the Treatment of Tendinopathy. J B J S(Am) 2012, 94, 143, 1-8
Suggest that PRP without leukocytes is a better choice for creating a lower catabolic cytokine environment and better stimulate cell proliferation and extracellular matrix production than high leukocyte PRP preparations, could be true, yet did not indicate whether IL-1beta and mmp-
13 were measured immediately or after 72 hour culture.(+)
28.) Mei-Dan O,*1" MD, Michael R. Garment,* FRCS(Tr&Orth), Lior Laver,1" MD, Gideon Mann;t§
MD, Nicola Maffulli,11 MD, MS, PhD, FRCS(Orth), and Meir Nyska,1" MD. Platelet-Rich Plasma or
Hyaluronate in the Management of Osteochondral Lesions of the Talus. American Journal of
Sports Medicine, Vol. 40, No. 3
PRP worked better than hyaluronic acid in ankle lesions(+)
29.) Milano G, M.D., Laura Deriu, M.D., Eraldo Sanna Passino, D.V.M., Gerolamo Masala, D.V.M.,
Andrea Manunta, M.D., Roberto Postacchini, M.D., Maristella F. Saccomanno, M.D., and Carlo
Fabbriciani, M.D. Repeated Platelet Concentrate Injections Enhance Reparative Response of
Microfractures in the Treatment of Chondral Defects of the Knee: An Experimental Study in an

Animal Model. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 5
(May), 2012: pp 688-701
PRP when added to microfracture makes better cartilage(+)
30.) Narita A, M.D., Ph.D., Masatoshi Takahara, M.D., Ph.D., Daisuke Sato, M.D., Toshihiko Ogino,
M.D., Ph.D., Shigenobu Fukushima, M.D., Yu Kimura, MJBng., Yasuhiko Tabata. Biodegradable
Gelatin Hydrogels Incorporating Fibroblast Growth Factor 2 Promote Healing of Horizontal Tears in Rabbit Meniscus. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 2
(February), 2012: pp 255-263
GHs incorporating FGF-2 significantly stimulated proliferation and inhibited the death of meniscal cells until 4 weeks, thereby increasing meniscal cell density and enhancing meniscal repair in a rabbit model
31.) Peerbooms JC,* MD, Jordi Sluimer,1" MD, Daniel J. Bruijn,* PhD, and Taco Go-sens,1* PhD.
Positive Effect of an Autologous Platelet Concentrate in Lateral Epicondylitis in a Double-Blind
Randomized Controlled Trial. American Journal of Sports Medicine, Vol. 38, No. 2, 2010
PRP better than cortisone injections for tennis elbow(+)
32.) Provenzano PP, Adriana L Alejandro-Osorio2, Kelley W Grorud1'3, Daniel A Martinez4'5, Arthur
C Vailas5, Richard E Grindeland6 Ray Vanderby Jr. Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments.
&MC Physiology 2007, 7:
Systemic HGH and IGF1 improved healing of collagen tissue(Hormone+)
33.) Radice F, M.D., Roberto Yanez, M.D., Vicente Gutierrez, M.D., Julio Resales, M.D.,
Miguel Pinedo, M.D., and Sebastian Coda, M.D. Comparison of Magnetic Resonance Imaging
Findings in Anterior Cruciate Ligament Grafts With and Without Autologous Platelet-Derived
Growth Factors. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 26, No 1
(January), 2010: pp 50-57
ACL grafts mature on MRI at 179 versus 369 days with PRP compared to without(+)
•
34.) Randelli P, MDa'*, Paolo Arrigoni, MDa, Vincenza Ragone, MEnga, Alberto Aliprandi, MDb, Paolo
Cabitza, MDa J. Platelet rich plasma in arthroscopic rotator cuff repair: A prospective RCT study,
2-year follow-up. Shoulder Elbow Surg (2011) 20, 517
Decreased pain and positively affected rotator cuff healing.(+)
35.) Sanchez M, Ph.D., Nicolas Fiz, Ph.D., Juan Azofra, Ph.D., Jaime Usabiaga, Ph.D., Enmanuel Aduriz
Recalde, Ph.D., Antonio Garcia Gutierrez, Ph.D., Javier Albillos, Ph.D.,Ramon Garate, Ph.D., Jose
Javier Aguirre, Sabino Padilla, Ph.D., Gorka Orive, Ph.D., and Eduardo Anitua, M.D., D.D.S., Ph.D.
A Randomized Clinical Trial Evaluating Plasma Rich in Growth Factors (PRGF-Endoret) Versus
Hyaluronic Acid in the Short-Term Treatment of Symptomatic Knee Osteoarthritis. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 28, No S (August), 2012: pp J070-1078
PRP was better than Hyaluronic Acid injections in mild and moderate osteoarthritis of the knee(+)
36.) Sanchez M, M.D., Eduardo Anitua, M.D., Juan Azofra, M.D., Roberto Prado, Ph.D.,Francisco
Muruzabal, Ph.D., and Isabel Andia, Ph.D. Ligamentization of Tendon Grafts Treated With an

Endogenous Preparation Rich in Growth Factors: Gross Morphology and Histology. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 26, No 4 (April}, 2010: pp 470-480
PRP provides for better graft remodeling(+)
37.) Sanchez M, Anitua E, Azofra J, Aguiree JJ, Andia A. Intra-Articular Injection of an Autologous
Preparation Rich in growth Factors for the Treatment of Osteoarthritis. Clinical Experimental
Rheumatology, 2008, 26, 910-913
PRP provides pain relief in Osteoarthritic Knees(+)
38.) Sheth U, BHSc, Nicole Simunovic, MSc, Guy Klein, DO, Freddie Fu, MD, Thomas A. Einhorn, MD,
Emil Schemitsch, MD, Olufemi R. Ayeni, MD, and Mohit Bhandari, MD, PhD. Efficacy of
Autologous Platelet-Rich Plasma Use for Orthopaedic Indications: A Meta-Analysis. J Bone Joint
Surg Am. 2012;94:298-
Studies lack standardization of preparations and outcomes(neutral)
39.) Thanasas C,*1" MD, George Papadimitriou,* MD, Charalambos Charalambidis,* MD, llias
Paraskevopoulos,* MD, and Athanasios Papanikolaou,* MD, PhD. Platelet-Rich Plasma Versus
Autologous Whole Blood for the Treatment of Chronic Lateral Elbow Epicondylitis. American
Journal of Sports Medicine, Vol. 39, No. 10,2011
PRP better than blood for tennis elbow(+)
40.) Vavken.P M.D., M.Sc.EZl. Patrick Sadoqhi. M.D.. Martha M. Murray. M.The Effect of Platelet
Concentrates on Graft Maturation and Graft -Bone Interface Healing in Anterior Cruciate
Ligament Reconstruction in Human Patients: A Systematic Review of Controlled Trials. 2011
Arthroscopy Association of North America.
ACL, PRP positive on graft maturation(+)
41.) West DWD; Stuart M. Phillips, PhU, FACSM. Anabolic Processes in Human Skeletal Muscle:
Restoring the Identities of Growth. Hormone and Testosterone. THE PHYSICIAN AND
SPOKTSMEDICINE* ISSN -0091-3847,October 2010, No.3. Volume 38
Growth Hormone stimulates connective tissue production and lean body mass(+)
42.) Zhang J, Wang J. Platelet-Rich Releasate Promotes Differentiation of Tendon Stem cells in
Tendon Cells. Am J Sports Med, Vol. 38, No. 12, 2010
PRP Clot Releasate pushes tendon stem cells to differentiate and produce extracellular matrix(+)
31 Positive Articles !
3 Negative !
7 Informative/Classification or Neutral !

Shoulder
1.) Randelli P, MDa'*, Paolo Arrigoni, MDa, Vincenza Ragone, MEnga, Alberto Aliprandi, MDb, Paolo
•
Cabitza, MDa J. Platelet rich plasma in arthroscopic rotator cuff repair: A prospective RCT study,
2-year follow-up. Shoulder Elbow Surg (2011) 20, 517
Decreased pain and positively affected rotator cuff healing.(+)
2.) Gumrna S, MD, PhD, Vincenzo Campagna, MD, Giancarlo Ferrazza, MD, Giuseppe Giannicola,
MD. Use of Platelet-Leukocyte Membrane in Arthroscopic.Repair of Large Rotator Cuff Tears. J
BoneJointSurgAm. 2D12;94:1345
PRP improves repair integrity(+)
3.) Castricini R,* MD, Umile Giuseppe Longo,1" MD, MSc, Massimo De Benedetto,* MD,Nicola
Panfoli,* MD, Piergiorgio Pirani,* MD, Raul Zini,* MD,Nicola Maffulli,§11 MD, MS, PhD,
FRCS(Orth), and Vincenzo Denaro,1 MD. Platelet-Rich Plasma Augmentation for Arthroscopic
Rotator Cuff Repair. e American Journal of Sports Medicine, Vol. 39, No. 2
PRFM did not improve healing of rotator cuff repair(-)
4.) Bergeson AG,* MD, Robert Z. Tashjian,*1" MD, Patrick E, Greis,* MD,Julia Crim;* MD, Gregory J.
Stoddard,* MPH, and Robert T. Burks,** MD. Effects of Platelet-Rich Fibrin Matrix on Repair
Integrity of At-Risk Rotator Cuff Tears. American Journal of Sports Medicine, Vol. 40, No. 2
PRFM(Cascade) did not help re-tear rates and did not increase functional outcome(-)
5.) Beck J, Evans D, Tonino P, Yong S, Callaci JJ. The Biomechanical and Histologic Effects of Platelet-
Rich Plasma on Rat Rotator Cuff Repairs. Am J Sports Med. Vol. 40 No. 9, 2012
Notes non PRP groups had higher failure strain at 7 days, PRP higher at 21 days, PRP had higher fibroblastic response and vascular response at each time and PRP had more linear aligned fibers at 21 days(+), aids in being cautious for the first 3 weeks with post-op therapy(+)
6.) Barber AF, M.D., Scott A. Harnack, M.D., Stephen J. Snyder, M.D., and Onur Hapa, M.D. Rotator
Cuff Repair Healing Influenced by Platelet-Rich Plasma Construct Augmentation. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 27, No 8 (August), 2011: pp 1029-1035
Lower re-tear rates(+)
Knee
1.) Vavken.P M.D., M.Sc.EZl. Patrick Sadoqhi. M.D.. Martha M. Murray. M.The Effect of Platelet
Concentrates on Graft Maturation and Graft -Bone Interface Healing in Anterior Cruciate
Ligament Reconstruction in Human Patients: A Systematic Review of Controlled Trials. 2011
Arthroscopy Association of North America.
ACL, PRP positive on graft maturation(+)
2.) Sanchez M, Anitua E, Azofra J, Aguiree JJ, Andia A. Intra-Articular Injection of an Autologous
Preparation Rich in growth Factors for the Treatment of Osteoarthritis. Clinical Experimental
Rheumatology, 2008, 26, 910-913
PRP provides pain relief in Osteoarthritic Knees(+)
3.) Sanchez M, M.D., Eduardo Anitua, M.D., Juan Azofra, M.D., Roberto Prado, Ph.D.,Francisco
Muruzabal, Ph.D., and Isabel Andia, Ph.D. Ligamentization of Tendon Grafts Treated With an
Endogenous Preparation Rich in Growth Factors: Gross Morphology and Histology. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 26, No 4 (April}, 2010: pp 470-480
PRP provides for better graft remodeling(+)

4.) Sanchez M, Ph.D., Nicolas Fiz, Ph.D., Juan Azofra, Ph.D., Jaime Usabiaga, Ph.D., Enmanuel Aduriz
Recalde, Ph.D., Antonio Garcia Gutierrez, Ph.D., Javier Albillos, Ph.D.,Ramon Garate, Ph.D., Jose
Javier Aguirre, Sabino Padilla, Ph.D., Gorka Orive, Ph.D., and Eduardo Anitua, M.D., D.D.S., Ph.D.
A Randomized Clinical Trial Evaluating Plasma Rich in Growth Factors (PRGF-Endoret) Versus
Hyaluronic Acid in the Short-Term Treatment of Symptomatic Knee Osteoarthritis. Arthroscopy:
The Journal of Arthroscopic and Related Surgery, Vol 28, No S (August), 2012: pp J070-1078
PRP was better than Hyaluronic Acid injections in mild and moderate osteoarthritis of the knee(+)
5.) Radice F, M.D., Roberto Yanez, M.D., Vicente Gutierrez, M.D., Julio Resales, M.D.,
Miguel Pinedo, M.D., and Sebastian Coda, M.D. Comparison of Magnetic Resonance Imaging
Findings in Anterior Cruciate Ligament Grafts With and Without Autologous Platelet-Derived
Growth Factors. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 26, No 1
(January), 2010: pp 50-57
ACL grafts mature on MRI at 179 versus 369 days with PRP compared to without(+)
6.) Filardo G, Kon E. Platelet Rich Plasma Injections for Degenerative Cartilage lesions and
Osteoarthritis.Knee Surg Sports Traumatology, 2011 19:528-535
PRP effective in alleviating symptoms up to 24 months, fell off around 9-12 months(+)
7.) Fallouh L, MD, PhD, Koichi Nakagawa, MD, PhD, Takahisa Sasho, MD, PhD, Momoko Aral, ME,
Sota Kitahara, MD, PhD, Yuichi Wada, MD, PhD, Hideshige Moriya, MD, PhD, Kazuhisa
Takahashi, MD, PhD. Effects of Autologous Platelet-Rich Plasma on Cell Viability and Collagen
Synthesis in Injured Human Anterior Cruciate Ligament. J Bone Joint Surg Am. 2010;92:2909-16
PRP enhanced cell viability , number and ACL extracellular collagen(+)
8.) de Almeida AM, MD, MS, Marco Kawamura Demange, MD, PhD,Marcel Faraco Sobrado,
Marcelo Bordalo Rodrigues, MD, Andre Pedrinelli MD, PhD, and Arnaldo Jose Hernandez MD,
PhD. Patellar Tendon Healing With Platelet-Rich Plasma. American Journal of Sports Medicine,
Vol. 40, No, 6
PRP, 7x baseline, showed decreased pain, better healing of patellar ligament donor site for
ACL(+)
9.) Anitua E, Sanchez M, Nurden AT, Zalduendo MM, de La Fuente M, Azofra J, Andia I. Platelet
Released Growth Factors Ehnace the Secretion of Hyaluronic Acid and Induce Hepatocyte
Growth factor in Ostoarthritic Patients. Rheumatology. 2007 Dec. 46(12)
PRP increases hyaluronic acid production by synovial cells but does not halt the effects of IL-
1beta(+)
10.) Baltzer AWA M.D.f, C. Moser M.D.f, S. A. Jansen M.D.§ and R. Krauspe M.D4. Autologous conditioned serum (Orthokine) is an effective treatment for knee Osteoarthritis. Osteoarthritis
and Cartilage (2009) 17,152-160
Autologous conditioned serum (ACS) was developed in the mid-1990s in an attempt to generate an injectable material enriched in endogenous IL-1 Ra as a novel therapeutic for OA. Meijer et a/.27 noted that exposure of bloodto glass beads elicits a vigorous, rapid increase in the synthesis of several anti-inflammatory cytokines, includingll_-1Ra.
This observation is the basis for producing ACS, which is injected into the affected joint in a series of six intra-articular injections given twice a week for 3 Weeks-, 2 year followup(+)

Ankle/Achilles
1.) Mei-Dan O,*1" MD, Michael R. Garment,* FRCS(Tr&Orth), Lior Laver,1" MD, Gideon Mann;t§
MD, Nicola Maffulli,11 MD, MS, PhD, FRCS(Orth), and Meir Nyska,1" MD. Platelet-Rich Plasma or
Hyaluronate in the Management of Osteochondral Lesions of the Talus. American Journal of
Sports Medicine, Vol. 40, No. 3
PRP worked better than hyaluronic acid in ankle lesions(+)
2.) de Jonge S,*1"* MD, Robert J. de Vos,* MD, PhD, Adam Weir,* MD, Hans T. M. van Schie,t§
DVM, PhD, Sita M. A. Bierma-Zeinstra^11 PhD, Jan A. N. Verhaar,1" MD, PhD, Harrie
Weinans,1"11 PhD, and Johannes L Tol,* MD, PhD. One-Year Follow-up of Platelet-Rich Plasma
Treatment in Chronic Achilles Tendinopathy. American Journal of Sports Medicine, Vol. 39, No.
Biomet PRP, no difference in outcomes and ultrasonography_subjective(-)
Elbow/Tennis Elbow
1.) Thanasas C,*1" MD, George Papadimitriou,* MD, Charalambos Charalambidis,* MD, llias
Paraskevopoulos,* MD, and Athanasios Papanikolaou,* MD, PhD. Platelet-Rich Plasma Versus
Autologous Whole Blood for the Treatment of Chronic Lateral Elbow Epicondylitis. American
Journal of Sports Medicine, Vol. 39, No. 10,2011
PRP better than blood for tennis elbow(+)
2.) Peerbooms JC,* MD, Jordi Sluimer,1" MD, Daniel J. Bruijn,* PhD, and Taco Go-sens,1* PhD.
Positive Effect of an Autologous Platelet Concentrate in Lateral Epicondylitis in a Double-Blind
Randomized Controlled Trial. American Journal of Sports Medicine, Vol. 38, No. 2, 2010
PRP better than cortisone injections for tennis elbow(+)
3.) Gosens T,*"1" MD, PhD, Joost C. Peerbooms,* MD, Wilbert van Laar,* and Brenda L, den
Oudsten,1". Ongoing Positive Effect of Platelet-Rich Plasma Versus Corticosteroid Injection in
Lateral Epicondylitis. American Journal of Sports Medicine, Vol. 39, No. 6, 2011
PRP better than cortisone even at 2 years(+)
Tissue
1.) Zhang J, Wang J. Platelet-Rich Releasate Promotes Differentiation of Tendon Stem cells in
Tendon Cells. Am J Sports Med, Vol. 38, No. 12, 2010
PRP Clot Releasate pushes tendon stem cells to differentiate and produce extracellular matrix(+)
2.) McCarrel T, Minas T, Fortier L. Optimization of Leukocyte Concentration in Platelet-Rich Plasma for the Treatment of Tendinopathy. J B J S(Am) 2012, 94, 143, 1-8
Suggest that PRP without leukocytes is a better choice for creating a lower catabolic cytokine environment and better stimulate cell proliferation and extracellular matrix production than high leukocyte PRP preparations, could be true, yet did not indicate whether IL-1beta and mmp-
13 were measured immediately or after 72 hour culture.(+)
3.) Mazzocca AD,*f MS, MD, Mary Beth R. McCarthy,1" BS, David M. Chowaniec,f Evan M. Dugdale,f
Derek Hansen,1" MD, Mark P. Cote,1 DPT, James P. Bradley,* MD,Anthony A. Romeo,§ MD,
Robert A. Arciero,1" MD, and Knut Beitzel,1" MA, MD. The Positive Effects of DifferentPlatelet-
Rich Plasma Methods onHuman Muscle, Bone, and Tendon Cells. American Journal of Sports
Medicine, Vol. 40, No. 8
Various PRP concentration can affect different cell targets
Osteoblasts. Proliferation was significantly increased by addition of PK.PLP compared with all controls (FBS low, FBS high,
Blood) (P < .05) (Figure 1). Addition of PRPDSto osteoblasts led to significantly increased proliferation compared with all controls, native blood, and PRPfjp (P <.05). Proliferation was less when PRPjp was compared with PRPLp but did not reach statistical significance (P >.05). PRPHP showed significantly less proliferation compared with PRPDs CP < -05).
Myocytes. Proliferation was significantly increased by addition of PR?LP compared with, native blood (P !< .05)(Figure 2). Adding
PRPos or PRPHp to myocytes showedno significant increase in proliferation compared with the controls or the other separations.

Tenocytes. Proliferation was significantly increased by addition of PR?LP compared with all controls (FBS low,FBS high, Blood) (P <
.05) (Figure 3). There was no differencein the proliferation of tenocytes comparing all 3 PRP types. Addition of PRPDs showed a significant increase compared with the controls and native blood. For tenocytes, there was a significant increase (P < .05) seen when
PRPHp was added compared with the controls and native "blood but not compared with the other separations(+)
4.) Harrison S,* Patrick Vavken,* MD, Sherwin Kevy,f MD, May Jacobson,* PhD, David Zurakowski,*
PhD, and Martha M, Murray,** MD. Platelet Activation by Collagen Provides Sustained Release of Anabolic Cytokines. AJSM, 2011
Collagen sustains a release, thrombin immediate(neutral)
5.) Fratalocchi F, PHT, Alessandra Milani, MS, and Franco Postacchini,
Hyunchul Jo C,*1" MD, Ji Eun Kim,1" MS, Kang Sup Yoon,1 MD, and Sue Shin,* MD. Platelet-
Rich Plasma Stimulates Cell Proliferation and Enhances Matrix Gene Expression and
Synthesis in Tenocytes From Human Rotator Cuff Tendons With Degenerative Tears.
American Journal of Sports Medicine, Vol. 40, No. 5
PRP stimulated tenocyte cell proliferation and production of tendon extracellular matrix(+)
6.) Dragoo JL,*1" MD, Hillary J. Braun. Comparison of the Acute Inflammatory ! Response of Two
Commercial Platelet-Rich Plasma Systems in Healthy Rabbit Tendons. The American Journal of
Sports Medicine, Vol. 40, No.
5 days after injections L-PRP more inflammation than Cascade, at 14 days the same(-/+)
7.) Beck J, Evans D, Tonino P, Yong S, Callaci JJ. The Biomechanical and Histologic Effects of Platelet-
Rich Plasma on Rat Rotator Cuff Repairs. Am J Sports Med. Vol. 40 No. 9, 2012
Notes non PRP groups had higher failure strain at 7 days, PRP higher at 21 days, PRP had higher fibroblastic response and vascular response at each time and PRP had more linear aligned fibers at 21 days(+), aids in being cautious for the first 3 weeks with post-op therapy(+)
8.) Baboldashti NZ,*1"* MSc, Raewyn C. Poulsen,* PhD, Sarah L. Franklin,* PhD,
Mark S. Thompson,1"* MEng, PhD, and Philippa A. Hulley,* PhD. Platelet-Rich Plasma Protects
Animals
Tenocytes From Adverse Side Effects of Dexamethasone and Ciprofloxacin. American Journal of
Sports Medicine, Vol. 39, No. 9
Ciprofloxacin can cause tenocyte cell death, dexamethasone can cause tenocyte senescence-
PRP protects(+)
1.) Provenzano PP*1, Adriana L Alejandro-Osorio2, Kelley W Grorud1'3, Daniel A Martinez4'5,
Arthur C Vailas5, Richard E Grindeland6 Ray Vanderby Jr*1. Systemic administration of IGF-I enhances healing in collagenous extracellular matrices: evaluation of loaded and unloaded ligaments. &MC Physiology 2007, 7:
Systemic HGH and IGF1 improved healing of collagen tissue(Hormone+)
2.) Milano G, M.D., Laura Deriu, M.D., Eraldo Sanna Passino, D.V.M., Gerolamo Masala, D.V.M.,
Andrea Manunta, M.D., Roberto Postacchini, M.D., Maristella F. Saccomanno, M.D., and Carlo
Fabbriciani, M.D. Repeated Platelet Concentrate Injections Enhance Reparative Response of
Microfractures in the Treatment of Chondral Defects of the Knee: An Experimental Study in an
Animal Model. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 5
(May), 2012: pp 688-701
PRP when added to microfracture makes better cartilage(+)
3.) Kisiday JD, C., Wayne Mcllwraith, William G. Rodkey, David D. Frisbie, J.Richard Steadman.
Effects of Platelet-Rich Plasma Composition on Anabolic and Catabolic Activities inEquine
Cartilage and Meniscal Explants. Cartilage.3(3) 245-254
Suggests that Leukocytes may not be good for joints- IL-1beta its effect? Not solid study-in vitro(?)

4.) Getgood A, Henson F, Skelton C, herrara E, Brooks R, Fortier L, Rushton N. The Augmentation of a Collagen/Glycosaminoglycan Biphasic Osteochondral Scaffold with Platelet-Rich Plasma and
Concentrated Bone Marrow Aspirate for Osteochondral Defect Repair in Sheep. Cartilage 3(4),
2012 351-363
PRP creates better hyaline-like cartilage than controls, PRP/BMAC better hyaline-like cartilage than controls and less subchondral bone cyst formation(+)
5.) Majewski,*1" MD, Peter E. Ochsner,* MD, Fanjun Liu,§ PhD, Rudolf Fluckiger,§ PhD, and Christopher H. Evans,§ PhD. Accelerated Healing of the Rat Achilles
Tendon in Response to Autologous Conditioned Serum AM J Sports Med, Vol. 37 No. 11, 2009
ACS makes tendon stronger(+)
6.) Narita A, M.D., Ph.D., Masatoshi Takahara, M.D., Ph.D., Daisuke Sato, M.D., Toshihiko Ogino,
M.D., Ph.D., Shigenobu Fukushima, M.D., Yu Kimura, MJBng., Yasuhiko Tabata. Biodegradable
Gelatin Hydrogels Incorporating Fibroblast Growth Factor 2 Promote Healing of Horizontal Tears in Rabbit Meniscus. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 2
(February), 2012: pp 255-263
GHs incorporating FGF-2 significantly stimulated proliferation and inhibited the death of meniscal cells until 4 weeks, thereby increasing meniscal cell density and enhancing meniscal repair in a rabbit model
Muscle
1.) West DWD; Stuart M. Phillips, PhU, FACSM. Anabolic Processes in Human Skeletal Muscle:
Restoring the Identities of Growth. Hormone and Testosterone. THE PHYSICIAN AND
SPOKTSMEDICINE* ISSN -0091-3847,October 2010, No.3. Volume 38
Growth Hormone stimulates connective tissue production and lean body mass(+)
Meta-Analysis
1.) Sheth U, BHSc, Nicole Simunovic, MSc, Guy Klein, DO, Freddie Fu, MD, Thomas A. Einhorn, MD,
Emil Schemitsch, MD, Olufemi R. Ayeni, MD, and Mohit Bhandari, MD, PhD. Efficacy of
Autologous Platelet-Rich Plasma Use for Orthopaedic Indications: A Meta-Analysis. J Bone Joint
Surg Am. 2012;94:298-
Studies lack standardization of preparations and outcomes(neutral)
Classification/Advise
1.) Mazzocca AD, MS, MD, Mary Beth R. McCarthy, BS, David M. Chowaniec, BS, Mark P. Cote, DPT,
Anthony A. Romeo, MD, James P. Bradley, MD, Robert A. Arciero, MD, and Knut Beitzel, MD.
Platelet-Rich Plasma Differs According to Preparation Method and Human Variability. J Bone
Joint Surg Am. 2012; 94:308-16
Preparation methods varied with content and multiple samples from same patient showed significant variability(neutral
)
2.) Foster TE, *f MD, Brian L Puskas,1" MD, Bert R. Mandelbaum,* MD, Michael B. Gerhardt,* MD, and Scott A, Rodeo,§ MD. Platelet-Rich Plasma From Basic Science to Clinical Applications.
American Journal of Sports Medicine, Vol. 37, No. 11, 2009
Review- initially anti-doping agencies against but now have switched(+)
3.) Ehrenfest DMD, Lars Rasmusson and Tomas Albrektsson. Classification of platelet concentrates: from pure platelet-rich plasma (P-PRP) to leucocyte- and platelet-rich fibrin (L-PRP). Trends in
Biotechnology Vol.27 No.3, 2009
Classification System of PRP(neutral)
4.) DeLong MJ, B.Sc., Ryan P. Russell, M.A., and Augustus D. Mazzocca, M.S., M.D. Platelet-Rich
Plasma: The PAW Classification System. Arthroscopy: The Journal of Arthroscopic and Related
Surgery, Vol 28, No 7 (July), 2012: pp 99S-I009

5.)
6.)
Classification includes platelet numbers, activation and white blood cell count(Neutral)
Castillo TN,* Michael A. Pouliot,* MD, Hyeon Joo Kim,* PhD, and Jason L. Dragee,*1" MD.
Comparison of Growth Factor and Platelet Concentration From Commercial Platelet-Rich Plasma Separation Systems. American
Journal of Sports Medicine, Vol. 39, No. 2
Various systems make various concentration(neutral)
Carofino B, M.D., David M. Chowaniec, B.S., Mary Beth McCarthy, B.S.,James P. Bradley, M.D.,
Steve Delaronde, M.P.H., M.S.W., Knut Beitzel, M.D.,Mark P. Cote, P.T., D.P.T., Robert A. Arciero,
M.D., and Augustus D. Mazzocca, M.S., M.D. Corticosteroids and Local Anesthetics Decrease
Positive Effects of Platelet-Rich Plasma: An In Vitro Study on HumanTendon Cells. Arthroscopy: The Journal of Arthroscopic and
Related Surgery, Vol 28, No 5 (May), 2012: pp 711-719 local anesthetics and steroids decrease cell proliferation and viability of tenocytes with prp(neutral)
1.) Agung M, Ochi M. Mobilization of Bone Marrow Derived Stem Cells into the Tissue After Intraarticular Injection and their Contribution to tissue Regeneration. Knee Surg Traumatol
Arthroscopy, 2006, 14, 1307
BMSCs migrate to injured tissue(+)
2.) Ahmad Z B.Sc., M.B.B.S., M.R.C.S., John Wardale, Ph.D., Roger Brooks, Ph.D., Fran Henson, Ph.D.,
All Noorani, B.Sc., F.R.C.S., and Neil Rushton, M.D., F.R.C. Exploring the Application of Stem Cells in Tendon Repair and Regeneration. Arthroscopy: The Journal of Arthroscopic and Related
Surgery, Vol 28, No 7 (July), 2012: pp 10] 8-1029
Positive 25 studies reviewed(summary)
3.) Beitzel K, M.A., M.D., Mary Beth McCarthy, B.S., Mark P. Cote, P.T., D.P.T., David Chowaniec,
B.S., Lauryn M. Falcone, Justine A. Falcone, Evan M. Dugdale, Thomas M. DeBerardino, M.D.,
Robert A. Arciero, M.D., and Augustus D. Mazzocca, M.S., M.D. Rapid Isolation of Human Stem
Cells (Connective Progenitor Cells) From the Distal Femur During Arthroscopic Knee Surgery.
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 1 (January), 2012: pp
74-84
Can gather stem cells here(+)
4.) Brunswick, MsD, Antonio Carlos Campos-de-Carvalho, PhD,Regina Coeli dos Santos Goldenberg,
PhD, and Joao Pedro Saar Werneck-de-Castro, PhD. Adipose-Derived Stem-Cell Treatment of Skeletal Muscle Injury. J Bone Joint Surg Am. 2012;94:609-17
Adipose derived stem cells increase muscle repair at 2 weeks but not at 4 weeks, suggesting a paracrine effect(+)
5.) Chen H,* PhD, Anik Chevrier,* PhD, Caroline D. Hoemann,*1" PhD, Jun Sun,* MD, Wei Ouyang,*
PhD, Michael D. Buschmann:*t§ PhD. Characterization of Subchondral Bone Repair for Marrow-
Stimulated Chondral Defects and Its Relationship to Articular Cartilage Resurfacing. American
Journal of Sports Medicine, Vol. 39, No. 8 , 2011
Deeper drilling had better cartilage stimulating Bmscs(+)
6.) Dutton A, Choong P. Enhancement of Meniscal Repair in the Avascuar Zone in a Rat Model with
Bmscs. JBJS (Br).2010, 92(1)
Histologic and macroscopic characteristics positive(+)

7.) Fortier LA, DVM, PhD, Hollis G. Potter, MD, Ellen J. Rickey, DVM, Lauren V. Schnabel, DVM, Li
Foong Foo, MD, Leroy R. Chong, MD, Tracy Stokol, BVSc, PhD, Jon Cheefham, VetMB, PhD, and
Alan J. Nixon, BVSc, MS. Concentrated Bone Marrow Aspirate Improves Full-Thickness Cartilage
Repair Compared with Microfracture in the Equine Model. J Bone Joint Surg Am. 2010;92:1927-
37
Add Bmscs to microfracture better than microfracture alone(+)
8.) Getgood A, Henson F, Skelton C, herrara E, Brooks R, Fortier L, Rushton N. The Augmentation of a Collagen/Glycosaminoglycan Biphasic Osteochondral Scaffold with Platelet-Rich Plasma and
Concentrated Bone Marrow Aspirate for Osteochondral Defect Repair in Sheep. Cartilage 3(4),
2012 351-363
PRP creates better hyaline-like cartilage than controls, PRP/BMAC better hyaline-like cartilage than controls and less subchondral bone cyst formation(+)
9.) Giannini S MD, Roberto Buda MD, Francesca Vannini MD, PhD, Marco Cavallo MD, Brunella
Grigolo PhD. One-step Bone Marrow-derived Cell Transplantation in Talar Osteochondral
Lesions Clin Orthop Relat Res 2009
Imporved functional scores (+)
10.) Gobbi AW, MD, Georgios Kamatzikos, MD, Vivek Mahajan, MD. The Use of Bone Marrow
Aspirate Concentrated for Full-thickness Knee Cartilage Lesions in a One-step Procedure: A
Prospective Study. AANA April 2011
Conclusion: This study showed that the use of autologous bone marrow derived and collagen
I/Ill matrix in a one-step procedure could represent an improvement on the currently available techniques for cartilage transplantation could be a viable technique in the treatment of grade IV knee chondral lesions.(+)
11.) Gulotta LV,*1" MD, David Kovacevic,* MD, Jonathan D. Packer,* MD,Xiang Hua Deng,* MD, and
Scott A. Rodeo,* MD. Bone Marrow-Derived Mesenchymal StemCells Transduced With Scleraxis
Improve Rotator Cuff Healing in a Rat Model. 2011 American Journal of Sports Medicine, Vol. 39,
No. 6
Theoretically, Secx may act through several mechanisms to promote tendon-to-bone healing.
Because it is a transcription factor, it is possible that gene transfer of Sex into MSCs causes differentiation of these cells into tenocytes, which results in more collagen production.
However, because there was also an increase in the amount of fibrocartilage as well as the material properties of the repaired tendons, we believe that Sex acts through a more complex signaling mechanism that directs the transition of tendon to bone through a cartilaginous transition zone. The mechanisms by which this occurs are just starting to be elucidated. Blitz et al2 showed that Scx regulates BMP-4 expression in tendon cells and directs the formation of the deltoid bone ridge that ultimately serves as its tendinous insertion site.(+)
12.) Kondo E,* MD, PhD, Kazunori Yasuda,*f MD, PhD, Taro Katsura,** DVM, PhD, Riku Hayashi;*§
MD, PhD, Chinatsu Azuma,*11 MD, PhD, and Harukazu Tohyama,* MD, PhD. Local
Administration of Autologous Synovium-Derived Cells Improve the Structural Properties of
Anterior Cruciate Ligament Autograft Reconstruction in Sheep. 2011, American Journal of Sports
Medicine, Vol. 39, No. 5
Synovial MScs and fibrin glue help prevent deterioration of ACL graft.(+)

13.) Murphy JM,1 David J. Fink,1 Ernst B. Hunziker,2 and Frank P. Barry. Stem Cell Therapy in a
Caprine Model of Osteoarthritis. ARTHRITIS & RHEUMATISM Vol. 48, No. 12, December 2003, pp
3«4-3474
Conclusion, Local delivery of adult mesenchymal stem cells to injured joints stimulates regeneration of meniscal tissue and retards the progressive destruction normally seen in this model of OA.Mesenehymal stem cells (MSCs) have the capacity(+)
14.) Marquass B,*1"* MD, Ronny Schulz,^ PhD, Pierre Hepp,1" MD, Matthias Zscharnack,*§ PhD,
Thomas Aigner," MD, Stefanie Schmidt,1" Frank Stein,1" Robert Richter,1" Georg Osterhoff,11
MD, Gabriele Aust,1" PhD, Christoph Josten,1" MD, and Augustinus Bader;§ MD. Matrix-
Associated Implantation of Predifferentiated Mesenchymal Stem Cells Versus Articular
Chondrocytes. American Journal of Sports Medicine, Vol. 39, No., 2011
Collagen hydrogels plus Bmscs better cartilage(+)
15.) Masjuddin,1" MD, S. Ab-Rahim,§ PhD, Pan Pan Chong,1 MSc, L, Selvaratnam," PhD, and T.
Kamarul. Treatment Outcomes of Alginate-Embedded Allogenic Mesenchymal Stem Cells
VersusAutologous Chondrocytes for the Repairof Focal Articular Cartilage Defects in a Rabbit
Model. Am j Sports Med 2012
Similareffectivenss as autologous chondrocytes for cartilage defects(+)
16.) Mazzocca AD,* MS, MD, Mary Beth R. McCarthy, BS, David M. Chowaniec, BS, Mark P. Cote, PT,
DPT, Robert A. Arciero, MD, and Hicham Drissi, PhD. Connective Tissue Progenitor Cells) From the Proximal Humerus During Arthroscopic Rotator Cuff Surgery. Am J Sports Med Vol. 38 No. 7
2010
Technique for isolation from proximal humerus(instructional+)
17.) Mcllwraith CW, B.V.Sc., Ph.D., D.Sc., David D. Frisbie, D.V.M., Ph.D., William G. Rodkey, D.V.M.,
John D. Kisiday, Ph.D., Natasha M. Werpy, D.V.M., Christopher E. Kawcak, D.V.M., Ph.D., and J.
Richard Ruiz-Iban MA, M.D., Ph.D., Jorge Diaz-Heredia, M.D., Ph.D., Ignacio Garcfa-Gomez,
Ph.D., Fausto Gonzalez-Lizan, M.D., Elena Elias-Martm, M.D., and Victor Abraira, Ph.D. The Effect of the Addition of Adipose-Derived Mesenchymal Stem Cells to a Meniscal Repair in the
Avascular Zone: An Experimental Study in Rabbits. Arthroscopy: The Journal of Arthroscopic and
Related Surgery, Vol 27, No 12 (December), 2011: pp 1688-1696
Add adipose derived stem cells to meniscus helps avascular zone healing(+)
18.) Mochizuki,1 MD, PhD, Koji Natsu,1" MD, Hiromichi Omae,f MD. Rotator Cuff Regeneration Using a Bioabsorbable Material With Bone Marrow-Derived Mesenchymal Stem Cells in a Rabbit
Model. 2012. American Journal of Sports Medicine, Vol. 40, No. 6
BMSCs able to make better tendon and tendon bone interface(+)
19.) Nejadnik H,* MD, James H. Hui,*1" MBBS, FRCS, FAMS, Erica Pei Feng Choong,* Bee-Choo Tai,§
PhD, and Eng Hin Lee,* MD, FRCS. Autologous Bone Marrow-Derived Mesenchymal Stem Cells
Versus Autologous Chondrocyte Implantation. American Journal of Sports Medicine, Vol. 38, No.
6
As effective as Carticel
20.) Obaid H,*f MBChB, FRCS, FRCR, and David Connell. Cell Therapy in Tendon Disorders OAE
What Is the Current Evidence? 2010 American Journal of Sports Medicine, Vol. 38, No. 10

Conclusion: With the limitation of the available evidence, the literature suggests that cell therapy is applicable and may be effective for the treatment of tendinopathy. However, further research into the precise biological mechanisms, long-term implications, and cost-effectiveness is needed.(+)
21.) Ota s,*1 MD, PhD, Kenji Uehara,*1" MD, PhD, Masahiro Nozaki,*t MDT PhD, Tetsuo
Kobayashi,*1 MD, PhD, Satoshi Terada,*f MD, Kimimasa Tobita;*"MD, Freddie H. Fu,1" MD, DSc, and Johnny Huard,*t§ PhD. Intramuscular Transplantation of Muscle-Derived Stem Cells
Accelerates Skeletal Muscle Healing After Contusion Injury via Enhancement of Angiogenesis.
2011, American Journal of Sports Medicine, Vol. 39, No. 9
Intra-muscular injection of MdNscs into injury muscle resulte din less scar formation(+)
22.) Steadman, M.D. Evaluation of Intra-Articular Mesenchymal Stem Cells to Augment Healing of
Microfractured Chondral Defects. Arthroscopy: The Journal of Arthroscopic and Related Surgery,
Vol 27, No 11 (November), 2011: pp 1552-1561
Better aggrecan secretion and cartilage firmness with this approach(+)
23.) Wei Y. Cartilage Regeneration of Adipose Derived Stem cells in Hybrid Scaffold, PLGA. Cell
Transplant, 2009
Positive cartilage regeneration
24.) Mechanobiology of Stem cell Chapter http://orthodoc.aaos.org/WilliamFBennettMD/Mechanobiology%20of%20Adult%20and%20Ste m%20Cells.pdf
24 Positive
No negative

Shoulder
1.) Mazzocca AD,* MS, MD, Mary Beth R. McCarthy, BS, David M. Chowaniec, BS, Mark P. Cote, PT,
DPT, Robert A. Arciero, MD, and Hicham Drissi, PhD. Connective Tissue Progenitor Cells) From the Proximal Humerus During Arthroscopic Rotator Cuff Surgery. Am J Sports Med Vol. 38 No. 7
2010
Technique for isolation from proximal humerus(instructional+)
Knee
1.) Beitzel K, M.A., M.D., Mary Beth McCarthy, B.S., Mark P. Cote, P.T., D.P.T., David Chowaniec,
B.S., Lauryn M. Falcone, Justine A. Falcone, Evan M. Dugdale, Thomas M. DeBerardino, M.D.,
Robert A. Arciero, M.D., and Augustus D. Mazzocca, M.S., M.D. Rapid Isolation of Human Stem
Cells (Connective Progenitor Cells) From the Distal Femur During Arthroscopic Knee Surgery.
Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 1 (January), 2012: pp
74-84
Can gather stem cells here(+)
2.) Gobbi AW, MD, Georgios Kamatzikos, MD, Vivek Mahajan, MD. The Use of Bone Marrow
Aspirate Concentrated for Full-thickness Knee Cartilage Lesions in a One-step Procedure: A
Prospective Study. AANA April 2011
Conclusion: This study showed that the use of autologous bone marrow derived and collagen
I/Ill matrix in a one-step procedure could represent an improvement on the currently available techniques for cartilage transplantation could be a viable technique in the treatment of grade IV knee chondral lesions.(+)
3.) Marquass B,*1"* MD, Ronny Schulz,^ PhD, Pierre Hepp,1" MD, Matthias Zscharnack,*§ PhD,
Thomas Aigner," MD, Stefanie Schmidt,1" Frank Stein,1" Robert Richter,1" Georg Osterhoff,11
MD, Gabriele Aust,1" PhD, Christoph Josten,1" MD, and Augustinus Bader;§ MD. Matrix-
Associated Implantation of Predifferentiated Mesenchymal Stem Cells Versus Articular
Chondrocytes. American Journal of Sports Medicine, Vol. 39, No., 2011
Collagen hydrogels plus Bmscs better cartilage(+)
4.) Nejadnik H,* MD, James H. Hui,*1" MBBS, FRCS, FAMS, Erica Pei Feng Choong,* Bee-Choo Tai,§
PhD, and Eng Hin Lee,* MD, FRCS. Autologous Bone Marrow-Derived Mesenchymal Stem Cells
Versus Autologous Chondrocyte Implantation. American Journal of Sports Medicine, Vol. 38, No.
6
As effective as Carticel

Ankle
1.) Giannini S MD, Roberto Buda MD, Francesca Vannini MD, PhD, Marco Cavallo MD, Brunella
Grigolo PhD. One-step Bone Marrow-derived Cell Transplantation in Talar Osteochondral
Lesions Clin Orthop Relat Res 2009
Imporved functional scores (+)
Animal
1.) Agung M, Ochi M. Mobilization of Bone Marrow Derived Stem Cells into the Tissue After Intraarticular Injection and their Contribution to tissue Regeneration. Knee Surg Traumatol
Arthroscopy, 2006, 14, 1307
BMSCs migrate to injured tissue(+)
2.) Brunswick, MsD, Antonio Carlos Campos-de-Carvalho, PhD,Regina Coeli dos Santos Goldenberg,
PhD, and Joao Pedro Saar Werneck-de-Castro, PhD. Adipose-Derived Stem-Cell Treatment of Skeletal Muscle Injury. J Bone Joint Surg Am. 2012;94:609-17
Adipose derived stem cells increase muscle repair at 2 weeks but not at 4 weeks, suggesting a paracrine effect(+)
3.) Chen H,* PhD, Anik Chevrier,* PhD, Caroline D. Hoemann,*1" PhD, Jun Sun,* MD, Wei Ouyang,*
PhD, Michael D. Buschmann:*t§ PhD. Characterization of Subchondral Bone Repair for Marrow-
Stimulated Chondral Defects and Its Relationship to Articular Cartilage Resurfacing. American
Journal of Sports Medicine, Vol. 39, No. 8 , 2011
Deeper drilling had better cartilage stimulating Bmscs(+)
4.) Dutton A, Choong P. Enhancement of Meniscal Repair in the Avascuar Zone in a Rat Model with
Bmscs. JBJS (Br).2010, 92(1)
Histologic and macroscopic characteristics positive(+)
5.) Fortier LA, DVM, PhD, Hollis G. Potter, MD, Ellen J. Rickey, DVM, Lauren V. Schnabel, DVM, Li
Foong Foo, MD, Leroy R. Chong, MD, Tracy Stokol, BVSc, PhD, Jon Cheefham, VetMB, PhD, and
Alan J. Nixon, BVSc, MS. Concentrated Bone Marrow Aspirate Improves Full-Thickness Cartilage
Repair Compared with Microfracture in the Equine Model. J Bone Joint Surg Am. 2010;92:1927-
37
Add Bmscs to microfracture better than microfracture alone(+)
6.) Getgood A, Henson F, Skelton C, herrara E, Brooks R, Fortier L, Rushton N. The Augmentation of a Collagen/Glycosaminoglycan Biphasic Osteochondral Scaffold with Platelet-Rich Plasma and
Concentrated Bone Marrow Aspirate for Osteochondral Defect Repair in Sheep. Cartilage 3(4),
2012 351-363
PRP creates better hyaline-like cartilage than controls, PRP/BMAC better hyaline-like cartilage than controls and less subchondral bone cyst formation(+)
7.) Gulotta LV,*1" MD, David Kovacevic,* MD, Jonathan D. Packer,* MD,Xiang Hua Deng,* MD, and
Scott A. Rodeo,* MD. Bone Marrow-Derived Mesenchymal StemCells Transduced With Scleraxis
Improve Rotator Cuff Healing in a Rat Model. 2011 American Journal of Sports Medicine, Vol. 39,
No. 6
Theoretically, Secx may act through several mechanisms to promote tendon-to-bone healing.
Because it is a transcription factor, it is possible that gene transfer of Sex into MSCs causes differentiation of these cells into tenocytes, which results in more collagen production.
However, because there was also an increase in the amount of fibrocartilage as well as the material properties of the repaired tendons, we believe that Sex acts through a more complex signaling mechanism that directs the transition of tendon to bone through a cartilaginous transition zone. The mechanisms by which this occurs are just starting to be elucidated. Blitz et

al2 showed that Scx regulates BMP-4 expression in tendon cells and directs the formation of the deltoid bone ridge that ultimately serves as its tendinous insertion site.(+)
8.) Kondo E,* MD, PhD, Kazunori Yasuda,*f MD, PhD, Taro Katsura,** DVM, PhD, Riku Hayashi;*§
MD, PhD, Chinatsu Azuma,*11 MD, PhD, and Harukazu Tohyama,* MD, PhD. Local
Administration of Autologous Synovium-Derived Cells Improve the Structural Properties of
Anterior Cruciate Ligament Autograft Reconstruction in Sheep. 2011, American Journal of Sports
Medicine, Vol. 39, No. 5
Synovial MScs and fibrin glue help prevent deterioration of ACL graft.(+)
9.) Murphy JM,1 David J. Fink,1 Ernst B. Hunziker,2 and Frank P. Barry. Stem Cell Therapy in a
Caprine Model of Osteoarthritis. ARTHRITIS & RHEUMATISM Vol. 48, No. 12, December 2003, pp
3«4-3474
Conclusion, Local delivery of adult mesenchymal stem cells to injured joints stimulates regeneration of meniscal tissue and retards the progressive destruction normally seen in this model of OA.Mesenehymal stem cells (MSCs) have the capacity(+)
10.) Masjuddin,1" MD, S. Ab-Rahim,§ PhD, Pan Pan Chong,1 MSc, L, Selvaratnam," PhD, and T.
Kamarul. Treatment Outcomes of Alginate-Embedded Allogenic Mesenchymal Stem Cells
VersusAutologous Chondrocytes for the Repairof Focal Articular Cartilage Defects in a Rabbit
Model. Am j Sports Med 2012
Similareffectivenss as autologous chondrocytes for cartilage defects(+)
11.) Mcllwraith CW, B.V.Sc., Ph.D., D.Sc., David D. Frisbie, D.V.M., Ph.D., William G. Rodkey, D.V.M.,
John D. Kisiday, Ph.D., Natasha M. Werpy, D.V.M., Christopher E. Kawcak, D.V.M., Ph.D., and J.
Richard Ruiz-Iban MA, M.D., Ph.D., Jorge Diaz-Heredia, M.D., Ph.D., Ignacio Garcfa-Gomez,
Ph.D., Fausto Gonzalez-Lizan, M.D., Elena Elias-Martm, M.D., and Victor Abraira, Ph.D. The Effect of the Addition of Adipose-Derived Mesenchymal Stem Cells to a Meniscal Repair in the
Avascular Zone: An Experimental Study in Rabbits. Arthroscopy: The Journal of Arthroscopic and
Related Surgery, Vol 27, No 12 (December), 2011: pp 1688-1696
Add adipose derived stem cells to meniscus helps avascular zone healing(+)
12.) Mochizuki,1 MD, PhD, Koji Natsu,1" MD, Hiromichi Omae,f MD. Rotator Cuff Regeneration Using a Bioabsorbable Material With Bone Marrow-Derived Mesenchymal Stem Cells in a Rabbit
Model. 2012. American Journal of Sports Medicine, Vol. 40, No. 6
BMSCs able to make better tendon and tendon bone interface(+)
13.) Steadman, M.D. Evaluation of Intra-Articular Mesenchymal Stem Cells to Augment Healing of
Microfractured Chondral Defects. Arthroscopy: The Journal of Arthroscopic and Related Surgery,
Vol 27, No 11 (November), 2011: pp 1552-1561
Better aggrecan secretion and cartilage firmness with this approach(+)
14.) Wei Y. Cartilage Regeneration of Adipose Derived Stem cells in Hybrid Scaffold, PLGA. Cell
Transplant, 2009
Positive cartilage regeneration
Classification/Technique
1.) Ahmad Z B.Sc., M.B.B.S., M.R.C.S., John Wardale, Ph.D., Roger Brooks, Ph.D., Fran Henson, Ph.D.,
All Noorani, B.Sc., F.R.C.S., and Neil Rushton, M.D., F.R.C. Exploring the Application of Stem Cells in Tendon Repair and Regeneration. Arthroscopy: The Journal of Arthroscopic and Related
Surgery, Vol 28, No 7 (July), 2012: pp 10] 8-1029
Positive 25 studies reviewed(summary)
2.) Obaid H,*f MBChB, FRCS, FRCR, and David Connell. Cell Therapy in Tendon Disorders OAE
What Is the Current Evidence? 2010 American Journal of Sports Medicine, Vol. 38, No. 10
Conclusion: With the limitation of the available evidence, the literature suggests that cell therapy is applicable and may be effective for the treatment of tendinopathy. However, further

research into the precise biological mechanisms, long-term implications, and cost-effectiveness is needed.(+)
3.) Ota s,*1 MD, PhD, Kenji Uehara,*1" MD, PhD, Masahiro Nozaki,*t MDT PhD, Tetsuo
Kobayashi,*1 MD, PhD, Satoshi Terada,*f MD, Kimimasa Tobita;*"MD, Freddie H. Fu,1" MD, DSc, and Johnny Huard,*t§ PhD. Intramuscular Transplantation of Muscle-Derived Stem Cells
Accelerates Skeletal Muscle Healing After Contusion Injury via Enhancement of Angiogenesis.
2011, American Journal of Sports Medicine, Vol. 39, No. 9
Intra-muscular injection of MdNscs into injury muscle resulte din less scar formation(+)
1.) Chen,* PhD, Anik Chevrier,* PhD, Caroline D, Hoemann,*1" PhD, Jun Sun,* MD, Wei
Ouyang,* PhD, and Michael D. Buschmann. Characterization of Subchondral Bone Repair for
Marrow-Stimulated Chondral Defects and Its Relationship to Articular Cartilage Resurfacing.
American Journal of Sports Medicine, Vol. 39, No. 8, 2011
Bone marrow stimulation does not reconstitute normal bone structure. Strategies that increase subchondral bone involvement in marrow stimulation could further benefit cartilage repair
2.) Cole BJ MD, MBA, Jack Fair,* MD, C. S. Winalski,§ MD, Timothy Hosea,11 MD; John
Richmond,11 MD, Bert Mandelbaum,* MD, and Patrick G. De Deyne,** MPT, PhD.
Outcomes After a Single-Stage Procedure for Cell-Based Cartilage Repair. American Journal of Sports Medicine, Vol. 39, No. 6, 2011
Cartilage fragments provide for reasonable cartilage repair(+)
3.) Cortese F, Michael McNicholas, Greg Janes, Scott Gillogly, Stephen P. Abelow, Antonio
Gigante, and Nicolo Coletti. Arthroscopic Delivery of the Matrix-Induced Autologous
Chondrocyte Implant:International Experience and Technique Recommendations. Cartilage
3(2) 156-164
Carticel can be done arthroscopically
4.) Fontana A, M.D., Alessan Federica Rosso, M.D. Bistolfi, M.D., Maurizio Crova, M.D, and
Giuseppe Massazza, Andrea Fontana, M.D., Alessan Federica Rosso, M.D. Arthroscopic
Treatment of Hip Chondral defects. Autolgous Chondrocyte Transplantation versus simple
Debridement. Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol 28, No 3
(March), 2012: pp 322-329
ACT works in the hip
5.) Jungmann,*1" MD, Gian M. Salzmann,1" MD, Hagen Schmal,1" MD, PhD, Jan M. Pestka,1"
MD, Norbert P. Sudkamp,1" MD, PhD, and Philipp Niemeyer. Autologous Chondrocyte
Implantation for Treatment of Cartilage Defects of the Knee. American Journal of Sports
Medicine, Vol. 40, No. 1, 2012 female gender (Cox survival fit: P = .033), (2) previous surgeries of the affected joint (P =
.002), (3) previous bone marrow stimulation (P = .041), and periosteum patch-covered

ACI (P = .028). An influence of patient age, body mass index (BMI), defect number, defect size, lesion origin, lesion location, parallel treatment, or smoking on the risk for reintervention could not be observed.
6.) Kon E," MD; Giuseppe Filardo, MD, Massimo Berruto,* MD, Francesco Benazzo,§ MD,
Giacomo Zanon,§ MD, Stefano Delia Villa," MD, and Maurilio Marcacci. A Prospective
Comparative Study of Arthroscopic Second-Generation Autologous Chondrocyte
Implantation Versus Microfracture. American Journal of Sports Medicine, Vol. 39, 2011
Compared to microfracture in high-level athletes, more durable over time, microfracture faster but deteriorates.
7.) Macmull S,*1" MBBS, MRCS (Eng), Michael T. R. Parratt,1 MBChB, MRCS (Ed), George
Bentley,1 Dsc MB, ChM, FRCS, F Med Sci, John A. Skinner,f FRCS (Orth), Richard W. J.
Carrington FRCS (Orth), Tim Morris. Autologous Chondrocyte Implantation in the Adolescent
Knee. American Journal of Sports Medicine, Vol. 39, No. 8, 2011
Results show that, in this particular group who received ACI, patients experienced a reduction in pain and significant improvement in postoperative function after ACI or
MACI. The authors believe that ACI is appropriate in the management of carefully selected adolescents with symptomatic chondrai and osteochondral defects.
8.) Nejadnik H,* MD, James H. Hui,*1" MBBS, FRCS, FAMS, Erica Pei Feng Choong,* Bee-Choo
Tai,§ PhD, and Eng Hin Lee,* MD, FRCS. Autologous Bone Marrow-Derived Mesenchymal
Stem Cells Versus Autologous Chondrocyte Implantation. American Journal of Sports
Medicine, Vol. 38, No. 6
As effective as Carticel
9 knees
1 hip
9.) Pestka JM, MD, Gerrit Bode,1" MD; Gian Salzmann,1 MD, Norbert P. Sudkamp,1" MD, PhD,
Philipp Niemeyer. Clinical Outcome of Autologous Chondrocyte Implantation for Failed
Microfracture Treatment of Full-Thickness Cartilage Defects of the Knee Joint. American
Journal of Sports Medicine, Vol. 40, 2012
Autologous chondrocyte implantation after failed microfracturing appears to be associated with a significantly higher failure rate and inferior clinical outcome when compared with ACI as a first-line treatment
10.) Steinwachs M, Lars Peterson, Vladimir Bobic, Peter Verdonk, Philipp Niemeyer. Cell-Seeded
Collagen Matrix-Supported Autologous Chondrocyte Transplantation (ACT-CS): A Consensus
Statement on Surgical Technique. 3(1)5-12
Describes technique

Identifiers
Symbols IL1RN; DIRA; ICIL-1RA; IL-1RN; IL-1ra; IL-1ra3; IL1F3; IL1RA; IRAP; MVCD4
External IDs OMIM: 147679 MGI: 96547 HomoloGene: 11163 GeneCards: IL1RN Gene
[show]Gene Ontology
Molecular function • interleukin-1 receptor binding
• interleukin-1, Type I receptor binding
• interleukin-1, Type II receptor binding
• interleukin-1 receptor antagonist activity
• interleukin-1 Type I receptor antagonist activity
• interleukin-1 Type II receptor antagonist activity
Cellular component • extracellular space
• intracellular
• nucleus
• cytoplasm
• centrosome
• plasma membrane
• vesicle
Biological process • negative regulation of cytokine-mediated signaling pathway
• chronic inflammatory response to antigenic stimulus
• lipid metabolic process
• acute-phase response
• immune response
• female pregnancy
• memory
• response to organic nitrogen
• negative regulation of glutamate secretion
• response to organic cyclic compound
• insulin secretion
• negative regulation of heterotypic cell-cell adhesion
• response to drug
• negative regulation of apoptotic process
• positive regulation of JUN kinase activity
• response to glucocorticoid stimulus
• negative regulation of interleukin-1-mediated signaling pathway
Sources: Amigo / QuickGO
RNA expression pattern

The interleukin-1 receptor antagonist (IL-1RA) is a protein that in humans is encoded by the IL1RN gene.[1][2]
IL-1RA was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories.[3] IL-1RA, is an agent that binds non-productively to the cell surface interleukin-1 receptor
(IL-1R). IL-1R is the same receptor that binds interleukin 1 (IL-1). Hence IL-1RA prevents IL-1 from sending a signal to that cell.
Contents [hide]
1 Function
2 Clinical significance
3 References
4 Further reading
5 External links
Function
IL-1RA is a member of the interleukin 1 cytokine family. IL1Ra is secreted by various types of cells including immune cells, epithelial cells, and adipocytes, and is a natural inhibitor of the proinflammatory effect of IL1β. [4]. This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. This gene and five other closely related cytokine genes form a gene cluster spanning approximately 400 kb on chromosome 2. Four alternatively spliced transcript variants encoding distinct isoforms have been reported.[5]
[edit] Clinical significanceA polymorphism of this gene is reported to be associated with increased risk of osteoporotic fractures[6] and gastric cancer.[7]
Mutations in the IL1RN gene results in a rare disease called deficiency of the interleukin-1–receptor antagonist (DIRA).[8] Variants of the IL1RN gene is also associated with risk of schizophrenia.[9][10]
Elevated levels of IL1RN has been found in serum of schizophrenia patients.[11]
An interleukin 1 receptor antagonist is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role. It is commercially produced as anakinra, which is a human recombinant form of IL-1RA. In terms of protein similarities, IL-1β is more closely related to IL-1RA than it is to IL- 1α. The amino acids that are identical between mature human IL-1α and mature IL-1β is 22% while it is 26% when comparing IL-1β to IL-1RA and only 18% when comparing IL-1α to IL-1RA.[3]