Animal Tissue Sharing
for the
Human Research Program
Jeffrey D. Smith
NASA Ames Research Center
HRP Science Management Office
50 Years Into the Space Age
There is much left to learn before we can go
Mars
36 million mi
NEA
Millions mi
L2
Lunar Return
Unknown
Distance
240,000 mi
180-300 mi
Beyond
Known
Extended ISS
Extended ISS
62 mi
6 Months
12 Months
Duration
3 Years
Animal research on Earth and in space will be critical to mission success
Waste Not Want Not
Tissue sharing maximizes utilization and scientific
return from unique animal tissues produced by rare,
complex and costly NASA research activities
Biospecimen Sharing:
A Long-standing International Collaboration
1960’s: US s (19 expts)
• Basic biological processes occur in the absence of gravity (Cell division, growth
and reproduction)
1970’s - present: Russian Biosatellites (145 expts)
• Fundamental processes of musculoskeletal atrophy and vestibular and
sensorimotor adaptation to spaceflight identified
• Radiation levels were shown to not affect biological functions seriously
Biosatellite
Bion
Foton
Recent Biospecimen Sharing
STS-131, STS-133, STS-135
Mouse
Immunology
Mouse
Immunology 2
Commercial Biomedical
Testing Module-3
Primary: Antigen-Specific CD4+
T Cell Priming and Memory
Response During Spaceflight
Primary: Effect of Space Flight
on Innate Immunity to
Respiratory Viral Infections
Primary: Focus on bone and
vascular atrophy; treatment with
Amgen commercial antibody
BSP:
BSP:
BSP:
10
separate investigations
10
separate investigations
32
separate investigations
Mouse Immunology
STS-131 Biospecimen Sharing Program
PRIMARY EXPERIMENT
• Millie Hughes-Fulford Ph.D., Northern California Institute for Research and Education
(NCIRE) University California San Francisco (UCSF): Antigen-Specific CD4+ T Cell Priming
and Memory Response During Spaceflight
BIOSPECIMEN SHARING
• Eduardo Almeida, Ph.D., NASA Ames Research Center: heart and bone cell proliferation
• Michael Delp Ph.D., University of Florida: arterial vascular structure
• David Fitzgerald Ph.D., Oregon Health & Science University: cartilage strength
• Alan R Hargens, PhD., UC San Diego: intervertebral disc morphology
• Larry Hoffman Ph.D., Geffen School of Medicine at UCLA: vestibular neural adaptation
• Maija Mednieks Ph.D., University of Connecticut Health Center: salivary gland secretion
• Joseph S. Tash, Ph.D., University of Kansas Medical Center: female reproductive organ
physiology
• Stavros Thomopoulos Ph.D., Washington University: tendons and their bone connections
• Boris S. Shenkman Ph.D., Institute of Biomedical Problems Moscow: soleus and anterior
tibial muscles
• Shin-ichi Usami Ph.D., University School of Medicine, Department of Otorhinolaryngology,
Matsumoto Japan: gene expression in the vestibular endorgans
Mouse Immunology 2
STS-133 Biospecimen Sharing Program
PRIMARY EXPERIMENT:
Roberto P. Garofalo, M.D. University of Texas Medical Branch Effect of Space Flight on Innate
•
Immunity to Respiratory Viral Infections
BIOSPECIMEN SHARING
•
Richard Boyle, Ph.D., NADA Ames Research Center: neurovestibular adaptation
•
Eduardo Almeida, Ph.D., NASA Ames Research Center: Tissue Degeneration factors
•
Michael Delp Ph.D., University of Florida: Arterial vascular strucure Remodeling
•
David Fitzgerald Ph.D., Oregon Health & Science University: articular cartilage
•
Alan R Hargens, PhD., UC San Diego: Spine Deconditioning
•
Larry Hoffman Ph.D., Geffen School of Medicine at UCLA: Synaptic Plasticity in Utricular Hair
Cells
•
Maija Mednieks Ph.D., University of Connecticut Health Center: Protein Expression in
Salivary Glands
•
Joseph S. Tash, Ph.D., University of Kansas Medical Center: Female Reproductive Health
•
Stavros Thomopoulos Ph.D., Washington University: tendon-to-bone insertion
•
Susana Zanello, Ph.D., Universities Space Research Association at NASA JSC: Effects of
microgravitiy on the rodent retina
Late Edition HRP Investigation
Commercial Biomedical Testing Module-3
STS-135 Biospecimen Sharing Program
•
Primary Experiments: BioServe Space Technologies & AMGEN Inc. team of
investigators performed experiments to assess a commercial antibody as a
novel anabolic therapy for prevention of spaceflight-induced skeletal fragility
in mice and to study space flight's affects on vascular atrophy in the hind
limbs of mice
STS-135 Biospecimen Sharing Program
Science Investigations
– Brain (Hargens, UC San Diego; Pecaut, Nelson, – Adrenals (Pecaut, Loma Linda)
Mao, Loma Linda )
– Femoral heads, Quadriceps, Skin (Fitzgerald
– Eyes (Zanello, USRA NASA,
Mao,
Loma LindaUSRA
)
Oregon
HealthJSC)
and Science University
Eyes
(Zanello,
NASA
– Lung (Garofalo, University of Texas Medical
– Tail (Hargens, UC San Diego)
Branch Galveston, Mao, Loma Linda)
– Heart, Soleus, EDL, TA (Harrison University of
– Kidneys. small intestine (Levi, University of
Colorado)
Colorado)
– Biceps brachii Triceps brachi (Ishihara, Kyoto
– Liver (Jonscher,
CO; Peacaut
and Distal
Tian,
University,
Japan NASA JSC)
Liver,Univ
Fecal
Pellets,
Colon
(Smith,
Loma Linda, Smith NASA JSC; Wotring, JSC
– Skin (Mao, Loma Linda; Terada. Institute of Space
Pharmacology USRA )
and Astronautical Science, JAXA
– Metatarsals (Almeida, NASA ARC)
– Uterine horn, ovaries, stomach (Tash, University
– Distal Tibia and Tarsus (Yokota, Indiana
of Kansas Medical Center
Spleen,
Thymus
(Sams
and
Crucian, NASA JSC)
University Purdue University)
– Distal Colon & Fecal Pellets (Smith NASA JSC)
– Thymus (Hughes-Fulford USCF & NCIRE;
– Salivary glands &1/4 the left ventricle (Mednieks,
Gridley, Loma Linda)
University of Connecticut Health Center)
– Spleen (Hughes Fulford USCF & NCIRE;,
– Humerus-rotator cuff-scapula units &Achilles
Pecaut Loma Linda)
tendon
calcaneus
units (Thomopoulos,
Liver
(Wotring,
USRA
NASA
JSC)
– EDL, TA and masseter muscle (Barton,
Washington University)
University of Pennsylvania
– Meniscus (Willey, Wake Forest School of
– Temporal Bones (Boyle NASA ARC, Hoffman
Medicine
UCLA, ShimiShinshu University, Japan
– Cerebral artery, mesenteric vein, heart, soleus (
Delp, University of Florida
STS-135 Biospecimen Sharing Program
Science Summary
Large-scale, tissue sharing activities require an orchestra of welltimed events and one mistake can flow down to effect multiple BSP
experiments
HOWEVER: all tissues and science achieved from BSP would be lost
if sharing was not a part of these rare and unique flight experiments
From Flight to Ground
Bringing BSP Down to Earth
• The need to share animal tissues from spaceflight is
clear and has been done for decades
• Ground-based research using complex methods
and/or expensive facilities can also produce unique
and valuable tissues for sharing
• Modern techniques have greatly reduced the
amount of tissue required to perform a given
experiment and analysis
• The number of animals necessary is determined by
statistical power analysis, leaving more tissues
potentially available for sharing
41 Ongoing HRP Animal Research Grants
Addressing Risks to Human Spaceflight
Risk Topic
Number
of Risks
Disciplines
Active
Animal
Research
4
Muscle, Cardiovascular, EVA
Performance, Vehicle Design
Low
Cognitive, Behavioral, and
Team Tasks
6
Behavioral, Sleep, Workload,
Teaming, Information, Vehicle Control
Low
Ensure Adequate Nutrition
2
Nutrition, Food System
Low
Physical Tasks
Protect the Crew from Environmental Hazards
Radiation
Bone
Immune
Other
Provide Adequate Medical
Care for the Crew
4
Carcinogenesis, Solar Particle Event,
CNS, Degenerative Tissue
High
3
Osteoporosis, Fracture, Intervertebral
Disk
Medium
2
Host-Microorganism Interaction,
Immune Response
Low
4
Lunar Dust, Renal Stone, Cardiac
Rhythm, Orthostatic Intolerance
Low
2
Treatment, Medication Efficacy
None
From NASA Task Book, 2010
NSRL at Brookhaven
• NSRL features a beam line dedicated to radiobiology research
and state-of-the-art specimen-preparation areas.
• ~1000 hrs of beam time per year for cell and animal research
• ~30 PIs will participate in the upcoming March 2012 session
TISSUE SHARING
• Ad hoc sharing is
common and strongly
encouraged
• Piggyback
experiments save
time, money and
animals
• Tissue archiving is
not currently done
• 12-15 current grants supported that involve mammalian research
• Recent success: NSBRI scientists teamed up to perform a single
irradation experiment together and each saved a significant amount
of funding on beam-time
TISSUE SHARING
• Ad hoc sharing is done
• Ad hoc experiments save
time, money and animals
• Tissue archiving is not
currently done
• Program-coordinated tissue
sharing is not currently
done
Types of Tissue Sharing Projects
Most
Formal
Most
Time, Cost,
Complexity
Open NRA
Invited competition
among scientists with
ongoing research
within scope
Scope for Program-led
HRP Tissue Sharing
Tissues archived, then
openly competed through
on-line forum
Least
Formal
Ad hoc among
scientists
Least
Time, Cost,
Complexity
A Process for HRP
Tissue Sharing Projects
Sharing Opportunity:
PI Communicates to HRP
Species, conditions, dates,
tissues to be used
BSP Proposals:
requests submitted to PI
or to a BSP coordinator
Review:
feasibility, merit, VASR,
alignment with HRP goals
Archive:
any additional valued
tissue is placed in a
tissue archive
BSP Tissue Collection:
on site by BSP PI or
collected, preserved,
shipped by BSP coordinator
Fresh: primary
Investigation
Complete
Archived:
tissue shipped
to BSP PI
Analysis and results
Ames Biospecimen
Storage Facility (BSF)
IWS Poster #4012, 4:30 pm
Wednesday
An Existing Archive and On-line Forum Capability
http://lsda.jsc.nasa.gov/
Biospecimens
http://lsda.jsc.nasa.gov/scripts/biospeci
mens/bio_search_start_adv.cfm/
Enter Search Criteria
Search for “Skeletal” Tissue
190 Unassigned Specimens Found
Tissue Type
Mission
Hardware
Click on
“Data Requests”
Select
“Tissue”
Results from Current HRP Tissue
Sharing Activities
HRP/NSBRI BSP
Metrics for Success
• What tissues have been collected/used
through BSP that would otherwise have been
lost?
• What HRP Elements’ Risks, Gaps, Tasks have
benefited from the results of BSP activities?
• What publications have resulted from BSP
activities?
• What Risks to Human Health in space have
been reduced/mitigated with contribution from
BSP activities?
Primary Benefits of Tissue Sharing
• Maximize use of rare and costly tissue products
from NASA-funded research
• Reduce overall cost of animal research
• Provide opportunities to generate pilot data and
test new hypotheses without large expenditure
of time or resources
• Allow new investigators opportunities to “enter
the field” in collaboration with experienced PIs
• Integrated physiology research is broadened
when tissues are shared
Challenges of Tissue Sharing
• Primary investigation and PI(s) requirements
cannot be compromised
• Secondary (Tissue Sharing) investigations
must be carefully coordinated
• Competing requests for shared tissues must
receive merit review for prioritization
• There is a cost of tissue sharing (time,
money and risk) and it must be worth the
benefit
Conclusions
• A History of Success: BSP Programs have benefited Space Biology
research for many years and they will continue to be an important part
of future spaceflight studies
• Potential for HRP: ongoing ground-based animal research has great
potential for benefit from organized tissue sharing activities
• Ad hoc Sharing is Good: tissue sharing among investigators should
continue to be encouraged, but ad hoc sharing may not maximize
tissue use for all complex and costly ground-based studies
• Program-led Sharing Saves Time & Money: a tissue sharing project
for HRP and NSBRI can maximize the use of unique animal tissues
and increase scientific return on investment for NASA
• Results Address HRP Risks: tissue sharing research can directly
address HRP risks to human spaceflight when, otherwise, those
tissues (and results) would have been lost
to
Share
Tissues