NASA - National Aeronautics and Space Administration

Overview | Description | Applications | Operations | Results | Publications | Images

Experiment/Payload Overview

Brief Summary

Commercial Biomedical Testing Module-3: STS-135 space flight's affects on vascular atrophy in the hind limbs of mice (CBTM-3-Vascular Atrophy) examines the effects of space flight on the skeletal bones of mice and the efficacy of a novel agent that may mitigate the loss of bone associated with space flight. Humans and animals have been observed to lose bone mass during the reduced gravity of space flight. CBTM-3-Vascular Atrophy specifically determines if there is a correlation between space flight induced altered blood supply to the bones and surrounding tissues with a resultant loss of bone mass.

Principal Investigator

Ron Midura, Ph.D., Cleveland Clinic Foundation, Cleveland, OH, United States

Co-Investigator(s)/Collaborator(s)

Noel Patrick McCabe, Ph.D., Cleveland Clinic Foundation, Cleveland, OH, United States

Caroline Androjna, , Cleveland Clinic Foundation, Cleveland, OH, United States

Payload Developer

Ames Research Center, Moffett Field, CA, United States

Sponsoring Space Agency

National Aeronautics and Space Administration (NASA)

Sponsoring Organization:

Information Pending

ISS Expedition Duration:

March 2011 - September 2011

Expeditions Assigned

27/28

Previous ISS Missions

A similar investigation, CBTM, flew round trip to the ISS on STS-108 during ISS Expedition 4. CBTM-2 flew round trip to the ISS on STS-118 during ISS Expedition 15. AEMs have flown on numerous Space Shuttle missions over the years.

^ back to top

---

Experiment/Payload Description

Research Summary

• The loss of bone mass during space flight remains a significant problem for human space flight, especially long-duration space flights.



• A variety of countermeasures has been tried but has not proven to be totally effective.



• A potential correlation between bone mass loss and blood supply to the bone has not been tested previously.



• Commercial Biomedical Testing Module-3: STS-135 space flight's affects on vascular atrophy in the hind limbs of mice (CBTM-3-Vascular Atrophy) is part of a suite of investigations that focus on the effects of space flight on bone, particularly skeletal bone.



• If a correlation between blood supply and bone mass is found, it opens new avenues of research into the mechanisms associated with skeletal physiology and regulation both during space flight and during ground-based bone disorders such as osteopenia, osteoporosis, spinal cord injury and others.

Description

Commercial Biomedical Testing Module-3: STS-135 space flight's affects on vascular atrophy in the hind limbs of mice (CBTM-3-Vascular Atrophy) only receives animals that have not received the therapeutic test agent. Therefore, CBTM-3-Vascular Atrophy compares untreated flight animals with animals that were held in AEM's on the ground during the flight. CBTM-3-Vascular Atrophy focuses on determining whether space flight results in vascular atrophy in the hind limbs leading to a decreased vascular presence and decreased blood supply to the bone and surrounding tissues. CBTM-3-Vascular Atrophy utilizes long bones of the animals provided postflight, specifically a region of the lower hindlimb at mid-calf; a 5-mm long region of interest (ROI) that includes portions of the tibia, fibula and attached skeletal muscles such as the soleus. The rationale for selecting this ROI is that unloading results in sarcopenia and osteopenia (muscle and bone mass loss) in this anatomical region. Samples of tissue are embedded in cryomedium, stained and examined for differences in vascular/blood supply, vessel tissue structure, and decalcification between flight and ground animals. Tissue sections from mouse lower hind limbs are also used to identify potential alterations in vascular cell gene expression as a consequence of space flight. Upon completion of the flight, the research team has access to the mice a few hours after landing.

Nine to ten week old female C57Bl6 mice fly onboard the STS-135 Space Shuttle mission in the CBTM-3 payload. The primary objective of this space mission is to evaluate a sclerostin antibody treatment to promote bone formation and mitigate bone loss in microgravity. This experiment is configured with three animal enclosure modules (AEMs) flown on STS-135 and an additional three AEMs that house ground control mice in the Space Life Sciences Laboratory at Kennedy Space Center. Each AEM contains ten mice.

^ back to top

---

Applications

Space Applications

If a correlation is found between blood supply to bone and bone mass regulation, new insights into the mechanisms governing how the body responds to skeletal unloading will undoubtedly result. Such insights may lead to new therapies for maintaining a healthy musculoskeletal system during long-duration space flights.

Earth Applications

As noted in the preceding paragraph, if a correlation is found between blood supply to bone and bone mass regulation, new insights into the mechanisms governing how the body responds to skeletal unloading will likely result, insights that might lead not only to new therapies for maintaining a healthy musculoskeletal system during long duration space flights, but also new therapies for treating muscle and bone wasting diseases on the Earth.

^ back to top

---

Operations

Operational Requirements

AEM's with ten mice each are requested for a late load (L-21 hours) and to be removed postflight within four hours of landing. During flight the crew is requested to conduct a daily health check of the animals, i.e., a visual observation through the Lexan lid of the AEMs. Unusual appearance of the animals is to be reported as soon as possible.

Operational Protocols

For this study nine to ten week old female C57Bl6 mice are launched on the space shuttle. Flight mice are treated once with a placebo vehicle or therapeutic agent approximately 24 hours before launch. Ground control mice are treated in the same manner but with a 48 hour offset. Ground control mice are housed under the same environmental conditions (temperature, light/dark cycle, humidity, oxygen levels and carbon dioxide levels) as the flight mice. All mice receive the same full access to food and water. Upon return to Earth, the AEMs are returned to the research team for analysis. Body weight is also measured preflight and postflight. Statistical comparisons will be made between the treated and control mice.

^ back to top

---

Results/More Information

Information Pending

^ back to top

---

Related Web Sites

BioServe Space Technology

Space Biosciences Division

^ back to top

---

Publications

^ back to top

---

Ground Based Results Publications

^ back to top

---

ISS Patent Publications

^ back to top

---

Related Publications

• Convertino V A,Physiological adaptations to weightlessness: effects on exercise and work performance Exercise and Sport Sciences Reviews 1990 18 119-166
• Morey-Holton E R,Globus R K,Kaplansky A ,Durnova G N,The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data Advances in Space Biology and Medicine 2005 10 7-40
• Hargens A R,Steskal J ,Johansson C ,Tipton C M,Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats The Physiologist 1984 27 S37-S38
• Tuday E C,Nyhan D ,Shoukas A A,Berkowitz D E,Simulated microgravity-induced aortic remodeling Journal of Applied Physiology 2009 106 2002-2008
• McDonald K S,Delp M D,Fitts R H,Effect of hindlimb unweighting on tissue blood flow in the rat Journal of Applied Physiology 1992 72 2210-2218
• Zhang L-F ,Mao Q-W ,Ma J ,Yu Z-B ,Effects of simulated weightlessness on arterial vasculature (an experimental study of vascular deconditioning) Journal of Gravitational Physiology 1996 3 5-8
• Ma J ,Zhang L-F ,Yu Z-B ,Zhang L-N ,Time course and reversibility of arterial vasoreactivity changes in simulated microgravity rats Journal of Gravitational Physiology 1997 4 4:P45-P46
• Delp M D,Colleran P N,Wilkerson M K,McCurdy M R,Muller-Delp J ,Structural and functional remodeling of skeletal muscle microvasculature is induced by simulated microgravity American Journal of Physiology - Heart and Circulatory Physiology 2000 278 H1866-H1873
• Gashev A A,Delp M D,Zawieja D C,Inhibition of active lymph pump by simulated microgravity in rats American Journal of Physiology - Heart and Circulatory Physiology 2006 290 H2295-H2308
• Doty S B,Morey-Holton E R,Durnova G N,Kaplansky A S,Cosmos 1887: morphology, histochemistry and vasculature of the growing rat tibia Journal of the Federation of American Societies for Experimental Biology 1990 4 16-23

^ back to top

---

Images

NASA Image: JSC2011-E029133 - STS-135 crew members, from the right are NASA astronauts Chris Ferguson, commander; Sandy Magnus and Rex Walheim, both mission specialists, participate in an Animal Enclosure Module (AEM) training session in the Jake Garn Simulation and Training Facility at NASA's Johnson Space Center.

+ View Larger Image