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ISS Research to Advance Health on Earth
• DR. BESS DAWSON-HUGHES, SENIOR SCIENTIST AND
DIRECTOR, BONE METABOLISM LABORATOR...
Using ISS to Study T Cell Activation
Dr. Millie Hughes-Fulford
milliehf@gmail.com
Infection in Spaceflight
• Apollo 7 all three crew members had a
cold.
• Apollo 13, one of the crew members
became ill wit...
Activation of T cells in the Immune System
The 3 Signals Required for Full T Cell Activation
Antigen/MHC
TCR/CD3
CD28
IL-2R
B7 (Accessory cell)
IL-2
(Autocrine
signa...
Experiment Housed in ESA
Kubic On board incubator
with 1 g control
SpaceX3 launch Tcell Activation in Aging
© 2016 Hughes-Fulford
© 2016 Hughes-Fulford
© 2016 Hughes-Fulford
Visualization of gene array chip
© 2016 Hughes-Fulford
© 2015 Hughes-Fulford
mRNA expression Heat Map from Activation of T cells in
Spaceflight
Immune Genes Regulated by Gravity
© 2015 Hughes-Fulford
Are T cells in other mammals activated normally
in spaceflight?
• Test the effects of microgravity in vivo in spaceflight ...
ANIMAL ENCLOSURE MODULE
Experimental Design for C57BL/6 mouse STS-131
T cell activation Experiment
Flight Mice (n=8) 22.01 +/- 0.85g
Ground Mice (...
mRNA Gene Array Heat Map analysis of Mouse T-cells
© 2016 Hughes-Fulford
Gene expression 10 hours after landing
Gene expression of Mouse T cells after Flight using qRTPCR
© 2016 Hughes-Fulford
Conclusions
• These data support a physiological dependence of the
immune system on gravity.
• These data also suggest tha...
2016 Hughes-Fulford
TRANSCRIPTION
TRANSLATION
TNFa
INFg
GMCSF
CCL3
• The messenger (mRNA) is
converted to protein through ...
miRNA Regulates Protein Synthesis
• The first miRNA was found in nematode C. elegans
in 1993 they were found in humans 200...
New mode of gene regulation: miRNA
© 2016 Hughes-Fulford
Is miRNA Regulated in the
Human Immune System?
Our early ISS experiments was designed to analyze RNA
expression we had an ...
Human T Cell Had Altered miR-21 in in Flight
© 2015 Hughes-Fulford
ISS Experiment Results: Gene Expression of
miR-21 Protein Targets
© 2015 Hughes-Fulford
© 2015 Hughes-Fulford
© 2016 Hughes-Fulford
Using microgravity, we discovered a new mechanism of
resolution of inflammation, this offers new ins...
Biological Drugs Act on the Immune System
T cell
Macrophage
B-cell
INFg , TNFa
IL-2Ra IL-2
CD-20
Top Biotech Biological Drugs Targeting
Small Immune Molecules
Drug Company Action Disease treated
1. Enbrel (Amgen) TNF in...
miRNA Regulates Protein Synthesis
• Seed sequence in the small microRNA matches to the
3” end of the messenger RNA and blo...
T cell Activation in Aging Experiment
SpaceX5 Launch
Experiment Housed in ESA
Kubic On board incubator
with 1 g control
© ...
Discovery of miRNAs downregulated
in 1-g Immune Activation are Missing
in SpaceX5 experiment
© 2016 Hughes-Fulford
Final Remarks
• Using the microgravity of International Space Station
National Laboratory, we have discovered a method of
...
HUGHES-FULFORD LABORATORY
UCSF,NCIREANDVAMCSANFRANCISCO
:
NCC-2-1086,NAG-2-1286,NIH-1aAgingand CASISGrants
Zurich Laborato...
Acknowledgements
• Lilly
Marty Cramer
Pam Mitchell
Ken Savin
• BioServe
• CASIS
• NASA
• Taconic
Eli Lilly and Company
We make medicines that help people live longer, healthier, more active lives
♦ Company founded May 1...
Skeletal Muscle Atrophy occurs with Many
Diseases
• Over 124 conditions/diseases have been associated with skeletal muscle...
Muscle Atrophy Represents a Large Unmet
Medical Need
• The only treatment currently for muscle atrophy is physical
therapy...
Mouse Models of Muscle Atrophy
• Mechanisms of muscle wasting highly conserved between mice and man
– Similar cell signali...
Evidence for Muscle Wasting in Mice under
Conditions of Microgravity
Species
Number
/group
Age at
onset
Duration
Days
Incl...
Rodent Research 3
• Goal: To determine if a novel investigational compound
is able to prevent the muscle wasting that is e...
Unique Features of RR-3
• Novel investigational compound (myostatin inhibitor)
• New strain of mice, Balb/c
• 6 week exper...
Experimental Design
Groups:
1. Baseline, n=10
2. Flight mice, control treated, n=10
3. Flight mice, drug treated, n=10
4. ...
Pre-flight Adjustments
• Mice acclimatized to drinking apparatus and food bars 4 weeks
prior to launch
• Mice acclimatized...
We have Lift-Off !
April 8, 2016
Life Onboard ISS
• Dragon docked 1 day 17 hours post-launch
• Mice moved into ISS habitat
Live Phase Measures: Grip Strength
Columbus Instruments, OH
Grip strength measured pre-flight, interim and
termination for...
Live Phase Measures: Body composition
• Body composition measured by DEXA (dual energy x-ray absorptiometry) at
interim (a...
Live Phase Measures:
Anaesthesia Recovery
• DEXA performed on anesthetized mice
• First time to perform anesthesia followe...
Termination Sampling
• Serum (cardiac puncture)
• Hindlimb put into formalin for later histology
measures
• Carcass frozen...
Later Measures
• Muscle weights (including gastrocnemius, quadriceps, soleus)
• Brain weights
• Muscle hindlimb histology,...
Myostatin - a regulator of
muscle mass
• Compound tested is a myostatin inhibitor
(LSN2478185, YN41)
– Myostatin is a grow...
Preliminary Results from Live Phase Study
– Muscle Function
♦ Grip strength in ground controls relatively stable
• Increas...
Preliminary Results from Live Phase Study
– Lean Mass (DEXA)
♦ Increase in lean mass seen with myostatin inhibitor
compare...
Preliminary Results from Live Phase Study
– Lean Mass (DEXA)
♦ Explanations for apparent lack of muscle wasting
• Are the ...
Next Steps
• Continue analysis of samples and data
• Use data to further understand effects of microgravity on skeletal mu...
Space BioManufacturing
Techshot, Inc.
Eugene Boland, PhD – Chief Scientist
Mechanical Devices will Keep Us Alive:
Until We Can Print the Replacements
3D Printing and Biology Makes Headlines
Modern medicine: Lab-grown genitals,
spray-on skin ... - NBC News
3-D printed live...
Reality of Organ Shortage*
• 120,206 People on transplant list in the USA
• 16,445 organs transplanted in first 6 months o...
What if One Day?
• Personalized Medicine was more than a better prescription?
• Stem Cell Therapy moved from the Wall Stre...
What is Bioprinting?
Cells
Polymers
Image File
Image Processing
Additives
Organs
Tissues
3D
Constructs
Image Rendering
Bio...
Development Team
•Project management (prime contractor), spaceflight hardware
development, integration and operation. Spac...
Relevant Technologies
• Techshot
• ADSEP bioreactor (STS-95 heart patch)
• ACT2
• MVP
• Substage illuminator
• Electrospin...
Relevant Sizes
Water Glucose Antibody Virus Bacteria Human Cell Period Heart
Nanometers
Nanotechnology
Range
Bioprinting
R...
What We Can Grow Today
Chang, et al. 2012, ATVB
ZERO G Experience
Technology Milestones*
• Month 8/15 – Parabolic/suborbital flights to
test enabling technologies in microgravity.
Key para...
ISS Research to Advance Health on Earth
ISS Research to Advance Health on Earth
ISS Research to Advance Health on Earth
ISS Research to Advance Health on Earth
ISS Research to Advance Health on Earth
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ISS Research to Advance Health on Earth

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In an era of increasing human longevity, it is becoming ever more critical to prioritize no only improved treatment of disease but also approaches for maintaining wellness to preserve the quality of life for aging adults. Spaceflight-induced physiological changes represent deviations from this state of wellness, with some changes serving as accelerated models of Earth-based conditions, including musculoskeletal disease, immune dysfunction, and delayed wound healing. This session will highlight research onboard the ISS National Lab that seeks to exploit these spaceflight-induced physiological effects to improve human health on Earth through studies that advance the prevention, detection, and treatment of disease. In parallel, spaceflight research and development efforts also seek to improve the human condition by employing the space environment to advance diagnostic tools and drug discovery, development and delivery systems.

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ISS Research to Advance Health on Earth

  1. 1. ISS Research to Advance Health on Earth • DR. BESS DAWSON-HUGHES, SENIOR SCIENTIST AND DIRECTOR, BONE METABOLISM LABORATORY, TUFTS UNIVERSITY • DR. MILLIE HUGHES-FULFORD, SCIENTIFIC ADVISOR TO THE UNDER SECRETARY OF THE DEPARTMENT OF VETERANS AFFAIRS, SAN FRANCISCO VA HEALTH CARE SYSTEM • ROSAMUND SMITH, RESEARCH FELLOW, BIOTECHNOLOGY DISCOVERY RESEARCH, ELI LILLY AND COMPANY • DR. EUGENE BOLAND, CHIEF SCIENTIST, TECHSHOT, INC. SPEAKERS:
  2. 2. Using ISS to Study T Cell Activation Dr. Millie Hughes-Fulford milliehf@gmail.com
  3. 3. Infection in Spaceflight • Apollo 7 all three crew members had a cold. • Apollo 13, one of the crew members became ill with a common bacteria which usually does not affect people with normal immune systems. • In all, 15 of the 29 Apollo astronauts had an infection either during flight or within one week after flight. (Biomedical Results of Apollo, Johnston, Dietlein, and Berry, NASA Washington, D.C. 1975 © 2016 Hughes-Fulford
  4. 4. Activation of T cells in the Immune System
  5. 5. The 3 Signals Required for Full T Cell Activation Antigen/MHC TCR/CD3 CD28 IL-2R B7 (Accessory cell) IL-2 (Autocrine signal) Anti-CD3 or Con A anti CD28 TNFa INFg Chemokines/Cytokines Inflammatory factors © 2016 Hughes-Fulford
  6. 6. Experiment Housed in ESA Kubic On board incubator with 1 g control SpaceX3 launch Tcell Activation in Aging
  7. 7. © 2016 Hughes-Fulford
  8. 8. © 2016 Hughes-Fulford
  9. 9. © 2016 Hughes-Fulford
  10. 10. Visualization of gene array chip © 2016 Hughes-Fulford
  11. 11. © 2015 Hughes-Fulford mRNA expression Heat Map from Activation of T cells in Spaceflight
  12. 12. Immune Genes Regulated by Gravity © 2015 Hughes-Fulford
  13. 13. Are T cells in other mammals activated normally in spaceflight? • Test the effects of microgravity in vivo in spaceflight in the mouse model on STS-131.
  14. 14. ANIMAL ENCLOSURE MODULE
  15. 15. Experimental Design for C57BL/6 mouse STS-131 T cell activation Experiment Flight Mice (n=8) 22.01 +/- 0.85g Ground Mice (n=8) 22.04 +/- 0.94g © 2015 Hughes-Fulford Spaceflight (n=8) Ground (n-8)
  16. 16. mRNA Gene Array Heat Map analysis of Mouse T-cells © 2016 Hughes-Fulford Gene expression 10 hours after landing
  17. 17. Gene expression of Mouse T cells after Flight using qRTPCR © 2016 Hughes-Fulford
  18. 18. Conclusions • These data support a physiological dependence of the immune system on gravity. • These data also suggest that this might be a common thread throughout the animal kingdom, since two mammalian immune systems that developed on this planet are dependent on gravity for full function. © 2016 Hughes-Fulford
  19. 19. 2016 Hughes-Fulford TRANSCRIPTION TRANSLATION TNFa INFg GMCSF CCL3 • The messenger (mRNA) is converted to protein through a process called translation. • It has long been known that the translation step is regulated by transcription factors in the promoter regions, however new data has proven that there is a second level of regulation by miRNA.
  20. 20. miRNA Regulates Protein Synthesis • The first miRNA was found in nematode C. elegans in 1993 they were found in humans 2004. © 2016 Hughes-Fulford • miRNAs act as binary switches turning protein translation on and off • MicroRNAs (miRNA) are small non-coding RNAs about 20 nucleotides in length
  21. 21. New mode of gene regulation: miRNA © 2016 Hughes-Fulford
  22. 22. Is miRNA Regulated in the Human Immune System? Our early ISS experiments was designed to analyze RNA expression we had an unusual finding- One miRNA was found to be differentially regulated. © 2016 Hughes-Fulford
  23. 23. Human T Cell Had Altered miR-21 in in Flight © 2015 Hughes-Fulford
  24. 24. ISS Experiment Results: Gene Expression of miR-21 Protein Targets © 2015 Hughes-Fulford
  25. 25. © 2015 Hughes-Fulford
  26. 26. © 2016 Hughes-Fulford Using microgravity, we discovered a new mechanism of resolution of inflammation, this offers new insight on the normal regulation of the immune response and a new way to approach treating immune disease.
  27. 27. Biological Drugs Act on the Immune System T cell Macrophage B-cell INFg , TNFa IL-2Ra IL-2 CD-20
  28. 28. Top Biotech Biological Drugs Targeting Small Immune Molecules Drug Company Action Disease treated 1. Enbrel (Amgen) TNF inhib RA 2. Rituxan (Genentech) a CD20 leukemia 3. Humira (Abbott) TNF inh RA 4. Remicade (J & J) a TNFa autoimmune dis 5. Gleevec (Novartis) T. K. inhibitor leukemia 6. Neulasta (Amgen) CSF stimulates marrow © 2016 Hughes-Fulford
  29. 29. miRNA Regulates Protein Synthesis • Seed sequence in the small microRNA matches to the 3” end of the messenger RNA and blocks it translation. • We are activity searching for the regulators of inflammatory molecular regulators of © 2016 Hughes-Fulford
  30. 30. T cell Activation in Aging Experiment SpaceX5 Launch Experiment Housed in ESA Kubic On board incubator with 1 g control © 2016 Hughes-Fulford
  31. 31. Discovery of miRNAs downregulated in 1-g Immune Activation are Missing in SpaceX5 experiment © 2016 Hughes-Fulford
  32. 32. Final Remarks • Using the microgravity of International Space Station National Laboratory, we have discovered a method of finding the pivotal points of miRNA regulation thereby providing us with new pharmaceutical targets for treatment of immune dysfunction such as immuno- senescence in the elderly. • We will seek out miRNAs that can ameliorate the excessive immune response seen in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn’s diseases. © 2016 Hughes-Fulford
  33. 33. HUGHES-FULFORD LABORATORY UCSF,NCIREANDVAMCSANFRANCISCO : NCC-2-1086,NAG-2-1286,NIH-1aAgingand CASISGrants Zurich Laboratories Augusto Cogoli Isabelle Walters Università diSassari GraziaGalleri‡, MariaAntonia Meloni‡, ProtoPippia Many Thanks tothe NIH, CASIS, NASA and ESA Administration &Staff Hughes-Fulford Laboratory TaraCandelario Emily Martinez Tammy Chang,MD Marlene Grenon, MD JoeMessier JesusAguago JimBoonyaratanakornkit,Ph.D, MD ChaiFei Li,DVM Millie.Hughes-Fulford@ucsf.edu
  34. 34. Acknowledgements • Lilly Marty Cramer Pam Mitchell Ken Savin • BioServe • CASIS • NASA • Taconic
  35. 35. Eli Lilly and Company We make medicines that help people live longer, healthier, more active lives ♦ Company founded May 10, 1876 by U.S. Civil War veteran Colonel Eli Lilly ♦ Headquarters located in Indianapolis, Indiana, U.S.A. ♦ Approximately 40,000 employees worldwide ♦ Products marketed in 125 countries ♦ More than 8,000 employees engaged in research and development, or 20% of total workforce ♦ Lilly products treat cancer, depression, schizophrenia, diabetes, osteoporosis, psoriasis and many other conditions ♦ Expertise in musculoskeletal conditions • Osteoporosis, Muscle atrophy • Preclinical and clinical measures of bone and muscle • Myostatin inhibition
  36. 36. Skeletal Muscle Atrophy occurs with Many Diseases • Over 124 conditions/diseases have been associated with skeletal muscle wasting/atrophy • Includes certain forms of cancer, ALS, muscular dystrophy, sarcopenia, COPD, critical illness myopathy • And of course astronauts in space • Its not the size but the decrease in muscle function that is most critical to the patient • Decreased muscle power, strength, endurance • Decreased muscle function leads to diminished functional performance • Decreased ability to climb stairs, withstand medical treatments, perform activities of daily living • Increased chance of falls, injuries from falls, fractures, hospitalizations, death • Often leads to lack of independence • Associated with poor prognosis and outcomes
  37. 37. Muscle Atrophy Represents a Large Unmet Medical Need • The only treatment currently for muscle atrophy is physical therapy/exercise • May not be sufficient • Poor compliance with the ill/elderly • Is it possible to develop a drug to combat muscle atrophy? • Some drugs are working their way through clinical trials, but nothing near FDA approval
  38. 38. Mouse Models of Muscle Atrophy • Mechanisms of muscle wasting highly conserved between mice and man – Similar cell signaling pathways and key genes are involved • In drug discovery it is important to test compounds in mouse disease models before progressing into the clinic • Mouse models of muscle atrophy are not ideal – Unloading models, eg hindlimb suspension, limb casting – Tumor models – Genetic models eg SOD1 transgenic mice, mdx mice • In microgravity, muscles are ‘unloaded’ and evidence to date suggests they undergo atrophy
  39. 39. Evidence for Muscle Wasting in Mice under Conditions of Microgravity Species Number /group Age at onset Duration Days Included Measures Transporter Ref Rat Fisher 344 12 17 -5% BW; -24% gastroc Space shuttle Lalini et al 2000 Mouse C57Bl/6J 12 9 week 11 Decreased muscle CSA; - 5%BW from baseline; atrophy soleus> gastroc Space shuttle (Amgen) Harrison et al 2003 Mouse C57Bl/6J 12 9 week 13 -8.5% BW; decreased CSA particularly type II fibers (IIb, IIx). Soleus -30%; gastroc -15% wt.; masticater muscles not affected Space Shuttle (Amgen) Ferguson et al 2012; Sung et al 2013; Philippou et al 2015 RR-3 Mouse Balb/c 10 12 week 42 Body composition, grip strength ISS Lilly
  40. 40. Rodent Research 3 • Goal: To determine if a novel investigational compound is able to prevent the muscle wasting that is expected to occur on the ISS • Primary goal: – Use the results to help in discovery research to find ways to develop new medicines for patients in need with muscle wasting conditions • Secondary goals: – Continue to learn how animal cellular functions are affected by longer term microgravity
  41. 41. Unique Features of RR-3 • Novel investigational compound (myostatin inhibitor) • New strain of mice, Balb/c • 6 week experiment • Measure muscle function with grip strength meter • Anaesthesia followed by recovery on the mice to enable interim body composition measures • Body composition with DEXA Instrument (Bone Densitometer, TechSHOT), 2nd experiment to use this capability
  42. 42. Experimental Design Groups: 1. Baseline, n=10 2. Flight mice, control treated, n=10 3. Flight mice, drug treated, n=10 4. Ground control, control treated, n=10 5. Ground control, drug treated, n=10 Female Balb/c mice, approx 12 weeks of age at launch Duration of experiment= 6 weeks Ground controls offset 3 days from flight animals Animals randomized on body weight to groups Control and drugs delivered by sub-cutaneous injection at 0,2,4 weeks Treated and control mice mixed in each habitat (3,2) • Tail tattoo used for rapid identification of treatment (treated vs. control) • Mice identified by implanted microchip
  43. 43. Pre-flight Adjustments • Mice acclimatized to drinking apparatus and food bars 4 weeks prior to launch • Mice acclimatized to lack of bedding and wire floors 4 weeks prior to launch • Mice moved into Dragon habitat (10 mice/habitat) at L-24h
  44. 44. We have Lift-Off ! April 8, 2016
  45. 45. Life Onboard ISS • Dragon docked 1 day 17 hours post-launch • Mice moved into ISS habitat
  46. 46. Live Phase Measures: Grip Strength Columbus Instruments, OH Grip strength measured pre-flight, interim and termination for both flight and ground control mice • 4 measures taken per mouse per time point • 2 middle values averaged
  47. 47. Live Phase Measures: Body composition • Body composition measured by DEXA (dual energy x-ray absorptiometry) at interim (approx 4 weeks) and at termination (approx. 6 weeks) – Lean mass, fat mass, bone mineral content and density Bone scan of anesthetized mouse
  48. 48. Live Phase Measures: Anaesthesia Recovery • DEXA performed on anesthetized mice • First time to perform anesthesia followed by recovery on mice in space • Mixture of ketamine/xylazine used, followed by atipamezole to speed recovery • Mice kept separately in newly designed hardware (Anesthesia/Recovery System or ARS)
  49. 49. Termination Sampling • Serum (cardiac puncture) • Hindlimb put into formalin for later histology measures • Carcass frozen at -80oC • Samples due back to Earth in late August on SPX-9
  50. 50. Later Measures • Muscle weights (including gastrocnemius, quadriceps, soleus) • Brain weights • Muscle hindlimb histology, myofiber cross-sectional area • Muscle gene expression • Compound exposure (serum) • Bone parameters including biomechanics • Other measures still to be determined • Plan is to give unused tissues from control mice to other spaceflight researchers
  51. 51. Myostatin - a regulator of muscle mass • Compound tested is a myostatin inhibitor (LSN2478185, YN41) – Myostatin is a growth factor that is a negative regulator of muscle mass – Has been shown to prevent muscle wasting in terrestrial mouse models of muscle wasting (Smith et al 2015; unpublished) • A less specific inhibitor of myostatin, called ActRIIB- Fc, was tested by Amgen on a Space Shuttle mission (13 day flight) – Was able to reduce or prevent muscle wasting (Ferguson et al, 2012) Smith et al 2015 Indicates significance relative to the control p< 0.05. **
  52. 52. Preliminary Results from Live Phase Study – Muscle Function ♦ Grip strength in ground controls relatively stable • Increase at week 6 likely age-related increase in size ♦ Grip strength decreased in flight animals at week 4 • Recovered towards baseline by week 6 • Increase at week 6 likely due to age-related increase in size • Note different operator and orientation of grip strength meter of baseline vs weeks 4 and 6 measures ♦ In both ground control and flight animals myostatin inhibition significantly increased grip strength over control animals at both weeks 4 and 6 • To baseline values in flight animals • Above baseline values in ground controls Effects of myostatin inhibition on skeletal muscle function can occur under conditions of microgravity (*), refers to significance relative to its respective control at each time point, ($), refers to significance relative to the flight control group. All p values < 0.05. * * $ * $ *
  53. 53. Preliminary Results from Live Phase Study – Lean Mass (DEXA) ♦ Increase in lean mass seen with myostatin inhibitor compared to respective controls at both 4 and 6 weeks ♦ Ground and flight controls show increase in lean mass with time • Likely age related, as body weight increases with time for ground controls ♦ Surprisingly, flight controls did not have decreased lean mass compared to ground controls • Previous shuttle missions had shown loss of body weight, lean mass and individual hind limb muscles but these were earlier time points • Discordance with grip strength data RR-3 Lean Mass (DXA) Weeks 0 1 2 3 4 5 6 7 %ChangefromBaseline -5 0 5 10 15 20 25 Flight Control Flight YN41 Ground Control Ground YN41 * * * * (*), refers to significance relative to its respective control at each time point, All p values < 0.05. Effects of myostatin inhibition on skeletal muscle mass can occur under conditions of microgravity
  54. 54. Preliminary Results from Live Phase Study – Lean Mass (DEXA) ♦ Explanations for apparent lack of muscle wasting • Are the ground controls doing poorly? – Equivalent ground control experiment performed independently at Lilly in regular housing and results show ground controls performed as expected in terms of body weight gain • Wasting may have occurred earlier but mice recovered/overcompensated? • Fluid distribution in space affects DEXA readings? • Greater levels of altered types of exercise by flight animals? ♦ Important to get muscle weights to validate DEXA results ♦ Determine if changes in lean mass are seen in all or subset of muscles (*), refers to significance relative to its respective control at each time point, All p values < 0.05. Effects of myostatin inhibition on skeletal muscle mass can occur under conditions of microgravity * * * *
  55. 55. Next Steps • Continue analysis of samples and data • Use data to further understand effects of microgravity on skeletal muscle • Use data to assist drug discovery efforts to find drugs to combat muscle- wasting diseases
  56. 56. Space BioManufacturing Techshot, Inc. Eugene Boland, PhD – Chief Scientist
  57. 57. Mechanical Devices will Keep Us Alive: Until We Can Print the Replacements
  58. 58. 3D Printing and Biology Makes Headlines Modern medicine: Lab-grown genitals, spray-on skin ... - NBC News 3-D printed livers offer glimpse into the future ... - NBC News Father and Son Produce Leather via Bioprinting - VegNews Magazine Bioprinting cartilage into people is doctor's goal New bioprinting technique creates thicker, healthier tissue New Bioprinting Method Borrows Ancient Technique 3D bioprinting could spark ethical debate 3D Printing Reshapes Healthcare “ team of cardiovascular scientists has announced it will be able to 3D print a whole heart from the recipients' own cells within a decade."
  59. 59. Reality of Organ Shortage* • 120,206 People on transplant list in the USA • 16,445 organs transplanted in first 6 months of 2016 • 7,764 organ donors in the first 6 months of 2016 • For 2016, 1 person is added to list every 10 minutes • For 2016, 22 people die waiting each day All Data current as of 2:30 pm EDT 07/12/2016 as reported by the United Network of Organ Sharing (UNOS)
  60. 60. What if One Day? • Personalized Medicine was more than a better prescription? • Stem Cell Therapy moved from the Wall Street Journal and USA Today to Main Street even if it had to go to space first? • A child born with a congenital heart defect had only one surgery then grew up to be the best third baseman on his/her little league team instead on just watching sports? • Third Party Payers realized it is cheaper to fix a problem right the first time that prolong the wrong treatment?
  61. 61. What is Bioprinting? Cells Polymers Image File Image Processing Additives Organs Tissues 3D Constructs Image Rendering BioInk Dispensing Pen Transfer Language Bioprinter Pre-Fabricated Systems Structural Components
  62. 62. Development Team •Project management (prime contractor), spaceflight hardware development, integration and operation. Space medical solutions provider. Tissue bioprinter production management/supervision. •Pioneer in the Direct-Write 3D tissue printing field. Has expertise in Bioink and currently has a patent protected delivery system with the highest resolution and broadest dynamic range in terms of bioink capability. Supplier of delivery systems and control software integration partner.
  63. 63. Relevant Technologies • Techshot • ADSEP bioreactor (STS-95 heart patch) • ACT2 • MVP • Substage illuminator • Electrospinning device • n-Scrypt • Bioassembly Tool • Smart Pump • Dispenser pens • Catalog of 10,000+ printed materials
  64. 64. Relevant Sizes Water Glucose Antibody Virus Bacteria Human Cell Period Heart Nanometers Nanotechnology Range Bioprinting Range
  65. 65. What We Can Grow Today Chang, et al. 2012, ATVB
  66. 66. ZERO G Experience
  67. 67. Technology Milestones* • Month 8/15 – Parabolic/suborbital flights to test enabling technologies in microgravity. Key parameters include viscosity, cavitation potential / pressure gradient, cell viability, density gradient and thermal gradients. • Month 28 - ISS Technology Demonstration. Print a microvascularized tissue patch and return it for terrestrial evaluation. • Month 36 - ISS Experiment. Print a beating heart patch within bioreactor to mature the tissue. Tissue to contain arteriole, capillary bed and venule structures. Tissue will be perfused to demonstrate the ability for use as a transplant. *no NASA or CASIS funding or commitments have been implied or received in these forward looking statements

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