STEM CELLS IN
DENTISTRY
Presented By:
Dr. Sandeep (MDS 3rd year)
INTRODUCTION
Stem cells are a group of undifferentiated cells of biological nature that have
the capacity to differentiate into specialised cells and undergoes the process
of mitosis to produce newer cells.
These stem cells play a pivotal role in development and repair process.
The tissue repair mechanism in the body takes place with the help of
pleuripotent embryonic stem cells
later these cells develop into multipotent cells of varying origin like
epithelial, mesenchymal and other specific stem cells.
The embryonic stem cells of pleuripotent nature wither away with time,
however the differentiated multipotent adult stem cells lie deep within the
tissues and aid in repair when needed.
CHARACTERSTICS OF STEM CELLS
1) Totipotency – Can produce all the cell types in a body
including extraembryonic or placental cells.
EXAMPLES- Zygote, Early morula(day 2-3)
2) Pleuripotency – Can give rise to all types of cells that make up
the body, that is 3 germ layers- Ectoderm, Mesoderm,
Endoderm
EXAMPLES- Embryonic stem cells (found in the
inner mass cells of blastocyst) day 5-6
3) Multipotency – Can develop into more than one cell type but
are more limited than pleuripotent cells.
EXAMPLES- Haematopoietic stem cells, neural
stem cells,mesenchymal stem cells
PLEURIPOTENT CELLS
TOTIPOTENT CELLS
MULTIPOTENT STEM CELLS
Heamatopoietic lineage
Neural cell lineage
CLASSIFICATION OF STEM CELLS
EMBRYONIC STEM
CELLS
ADULT STEM
CELLS
INDUCED
PLEURIPOTENT
STEM CELLS
Embryonic stem cells
•Obtained from embryo that are 2-11 days old known as
blastocyst
•Have maximum potential to regenerate and repair unhealthy
organs and tissues in the body
ETHICAL ISSUE- the procedure of taking out stem cells from
an embryo wipe out the embryo itself and some view this as
taking life, thereby, increased ethical and moral concerns
TUMOROGENICITY- Since it is hard to control expansion and
differentiation of the embryonic stem cells , posing risk of
teratoma formation and tumorogenicity.
INNER CELL MEMBRANE
Induced pleuripotent stem cells
•They mimic embryonic stem cells in their
potential to divide.
•Produced via vectors(certain viruses), which
induce cell multiplication and cause growth of
undifferentiated cells
Adult stem cells
BY VIRUSES
Adult stem cells
These are undifferentiated cells that occur in differentiated tissues.
Sources- Bone marrow, Brain , Blood(neural stem cells), Eye(Retinal stem cells),
Dental pulp stem cells, stem cells from apical papilla, etc
Many types of adult stem cells reside in several mesenchymal tissues, thus
collectively referred to as MESENCHYMAL STEM CELLS (MSCs).
•Most promising type of stem cells for
clinical application
•Originally found in bone marrow, but
subsets also isolated from skin, adipose
tissues and various dental tissues
BONE MARROW DERIVED MSCs
•Possess a high replicative capacity and have capacity to differentiate into
various connective tissue cell types
BMSCs from iliac crest-
SITE
BONE MARROW ASPIRATION
•most commonly used for bone regeneration in
dental patients.
• BMSCs can be easily isolated from the bone
marrow of iliac crest but the procedure is
invasive for the donor
•BMSCs from human iliac crest may be
applicable to tissue engineering
irrespective of the age of the patient.
• With repeated culture of the same sample,
cells loose their differentiation capacity and
undergo senescence
Bone marrow stem cells can differentiate into adipocyes,
chondrocytes, and osteocytes
BMSCs from orofacial bones•Human BMSCs can also be isolated from orofacial bone
marrow aspirates obtained during dental surgical
procedures such as 3rd molar extraction and orthodontic
osteotomy.
• These can be obtained not only from younger patients but
also from relatively aged individuals (57-62 years).
Bone marrow stem cells from orofacial region
•Studies have indicated that grafted bone obtained from
craniofacial area for autologous bone grafting at the
same site provide better results, a compared to graft
obtained from other regions because of the similarity in
their origin.
• Embryologically, the maxilla and mandible bones
originate from neural crest cells whereas iliac crest
develops from mesoderm– this also results in functional
differences between them.
LIMITATION- the collectable volume of orofacial bone marrow is
less (0.03-0.5ml) than that of iliac crest (8- 13 ml)
TWO APPROACHES
Chair side cellular
grafting approach
Tissue engineering
approach
CHAIR SIDE CELLULAR GRAFTING APPROACHInvolves direct use of patient derived fresh cellular graft
prepared chair side.
Bone autograft- Bone directly grafted to recipient site.
 Bone marrow aspirate concentrate(BMAC)- chair side
cellular graft preparation using fresh aspirated bone marrow
from the ilium that is mixed with resorbable matrix,
transplanted with biocompatible scaffolds.
This has shown to form lamelar bone and thus provide reliable
base for dental implants.
ADVANTAGES•The cells in freshly processed grafts are not completely
homogenous, they contain several cell types such as- MSCs,
osteogenic cells, hematopoietc cells, angiogenic cells and
stromal cells. Thus behave similar to primitive bone niche
Thus easy acceptance by host environment without
unfavourable local inflammatory reaction.
LIMITATION•Less osteogenic potential, since quantity of stem cells is less(since it is not
expanded in-vitro)
•More donor site morbidity
TISSUE ENGINEERING APPROACHThis approach involves cell culture techniques to increase the number of
cells in vitro for later implantation to achieve bone tissue engineering.
Cells from aspirated bone marrow are expanded in vitro. These MSCs are
further cultured with osteogenic factors and a scaffold to generate an
osteogenic construct or cell sheets as grafting material.
Mixture of bone marrow MSCs and Plasma Rich Protein(PRP) in gel like
injectable form is used
Also bone marrow MSCs along with hydroxyapetite crystals or gelatin
sponge, or recombinant plasma derived growth factor(PGDF )can be used.
ADVANTAGES:
•High osteogenic potential(since more number of stem cells present)
•Low donor site morbidity
DENTAL TISSUE DERIVED
STEM CELLS
Dental epithelial
stem cells
The study of epithelial stem
cells in human teeth is
hampered by the fact that
dental epithelium is lost during
completion of tooth
development.
This is the reason that tooth
regeneration has not been
achieved in humans till date.
Dental mesenchymal
stem cells
Dental pulp derived stem
cells(DPSC)
Stem cells from human
exfoliated deciduous teeth(SHED)
Periodontal ligament stem
cells(PDLSC)
Dental follicle stem cells(DFSC)
Stem cells from apical part of
papilla(SCAP)
DENTAL MESENCHYMAL STEM CELLS
1) Dental pulp derived stem cells(DPSC)• most common source of dental tissue derived stem
cells and are obtained from pulp of permanent teeth.
• They are capable of differentiating into osteogenic,
odontogenic, myogenic, adipogenic components both
in-vivo and in-vitro.
2) Stem cells from Human Exfoliated Deciduous Teeth(SHED)
• Derived from exfoliated teeth
• More proliferative than DPSC
• They differentiate into neurogenic, adipogenic, and odontogenic
components and used for tissue regeneration involving orofacial
bony structures.
• Have capacity to produce bone and dentin
3) Periodontal ligament stem cells(PDLSC)•
•
Derived from seperated periodontal ligament from 3rd molars in
humans
Contain progenitors for self-renewal of oral structures like
cementum and bone.
4) Dental follicle stem cells(DFSC)• Derived from follicle surrounding human 3rd molars.
• Potential to differentiate into osteoblasts,
adipocytes, and neuroblats in vitro and periodontal
ligament in vivo.
5) Stem cells from apical papilla(SCAP)• Derived from apical part of developing tooth and have
high proliferative, migration and regenerative
capabilities
• They differentiate into pulp dentin complex.
ORAL MUCOSA DERIVED STEM CELLS
1)Oral epithelial stem cells- The oral mucosa is composed of stratified
squamous epithelium and oral epithelial stem cells are subpopulation
of small oral keratinocytes.
These are unipotent cells, ie can only develop into epithelial cells.
They possess clonogenicity and ability to regenerate a highly stratified
and well organised oral mucosal graft.
2) Human Gingiva derived MSCs(GMSCs)-
• present in lamina propria of gingiva
• they exhibit clonogenicity , self renewal and a
multipotent differentiation capacity.
•SALIVARY GLAND DERIVED STEM CELLS• patients afflicted with head and neck cancer , who receive
radiotherapy suffer from irreversible impairment of salivary
gland function that result in xerostomia and a compromised
state of life
•Thus stem cells in adult salivary gland are expected to be
useful for autologous transplantation therapy.
•LIMITATION- The salivary gland originate from endoderm and
consist of acinar and ductal epithelial cells with exocrine
function. So a stem cell that gives rise to all epithelial cell types
within the gland has not been identified.
ADIPOSE TISSUE DERIVED STEM CELLS•Abundant source of MSCs.
•Can be readily harvested via lipectomy or from liposuction from
areas such as chin, upper arms, abdomen, buttocks, hips and
thighs
•Procedure has low donor site morbidity but can be done only by
a physician
•They exhibit highosteogenic capacity thus expected to be an
alternative source of MSCs for bone regeneration in dentistry
Requirements of stem cells for
regenerative dentistry
1) Differentiation
capacity- the differentiation capacity of
adult MSCs is principally limited to mesenchymal leneages,
which hinders their application to reneration of complex oral
organs such as teeth and salivary glands, which are formed
during development by interaction of epithelial and
mesenchymal tissues.
A single stem cell with organogenic capacity has not been
identified in teeth and salivary glands
2) Accessibilty
• bone marrow aspiration from iliac crest and liposuction from
extra oral tissue is not an easy operation for dentist because
of limitation of the dental license.
•Only orofacial bone marrow, periosteum, salivary glands and
dental tissues are accessible stem cell sources for dentist.
•Gingiva is easily obtainable by dentist and whose cells can be
easily expanded from patients with minimal discomfort,
seems to be promising source of adult stem cells
3) Immunomodulationimmunomodulatory properties have been identified for MSCs
in animals and humans that may be related to therapeutic
effects such as angiogenesis, anti- inflammatory and anti
apoptosis.
MSCs have low inherent immunogenicity, thus make them
more attractive than other types of stem cells in cell
transplantation.
4) Survival of transplanted cells•Several studies have shown that transplanted cells die
quickly or migrate out of transplanted site.
•Survival of transplanted cells can be supported by sufficient
vascular supply, therefore, the cross talk between implanted
exogenous BMSCs and resident stem/ progenitor cells may
play a pivotal role in increasing vascularization in BMSC
implants to support cell survival and bone regeneration
ROLE OF HOST IMMUNE SYSTEM IN SURVIVAL OF STEM CELLS
APPLICATIONS IN PROSTHODONTICS
1) Tooth Regenerationo Epithelial mesenchymal exchange is mandatory in tooth
development( ECTOMESENCHYMAL INTERACTION).
o Three key elements are involved in tooth regeneration,
which include
 Inductive morphogenes
 Stem cells
 scaffold
o Since dental epithelium is lost during tooth development,
this interation cannot take place.
o The regeneration of adult teeth might be possible in
future with the help of tissue engineering and newer
expansion in stem cell therapy
2)
Alveolar bone augmentation-
The clinical effectiveness of stem cell therapies has mainly
been evaluated in alveolar ridge augmentation for insertion of
dental implants.
Currently clinical approaches to stem cell based bone augmentation has
been divided into 2 categories
Chair side cellular
grafting approach
Tissue engineering
approach
In both these approaches, bone marrow derived MSCs from iliac crest are most
commonly used stem cells.
A CLINICAL CASE OF STEM CELL BASED ALVEOLAR BONE REGENERATION FOR INSERTION OF
A DENTAL IMPLANT
3) Pulp revascularisation•Dependant on the ability of residual pulp and apical and periodontal stem
cells to differentiate.
•INDICATION- Presence of deep caries or trauma inducing a stop in the
development of root canal of an immature tooth
4 elements of this procedure:
 root canal disinfection
 stem cells (from apical papilla)
 scaffold
 coronal restoration
SCAFFOLD formed by blood clot (bleeding is induced by overinstrumentation)
STEM CELLS – Major role by “stem cells of apical papilla”
Dental stem cell banking
•It is a process of storing Stem cells obtained from patients deciduous
teeth and wisdom teeth in order to utilize them at a later stage and to
realize the potential of dental stem cell based regenerative therapy.
•Once stem cells containing tissue such as PDL, pulp tissues, apical papilla
are obtained from the patient, they can be cryopreserved for many years
to retain their regenerative potential.
•These autologous stem cells given to a patient would be recognized as
host cells and should therefore be tolerated by the immune system.
• Legislation for the banking system is necessary because it provides bioinsurance for future use
REFERENCES
1) Stem cells in dentistry- part 1: stem cell sources, Journal of Prosthodontic
Research (1 june 2012)
2) Stem cells in dentistry- part 2: clinical application, Journal of Prosthodontic
Research (20 september 2012)
3) Somatic stem cells in dentistry
Christian Morsczeck, Gottfried Schmalz, Torsten Eugen Reichert, Florian Vollner
4) Role of stem cells in Prosthontic Rehabilitation, Journal of Pharmaceutical
Sciences and Research,(vol.9, 2017, 497-500)
5) Dental Epithelial Stem Cells
Irma Thesleff and Emma Juuri
6) Dental pulp stem cells: what, where, how?
Alastair J. Sloan and Rachel J. Waddington
7) Iliac Crest Bone Graft Harvesting: Prospective study of various techniques
and donor site morbidity
S Kukreja, H Raza, A Agrawal
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