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Insight & Intelligence : Aug 15, 2011
Exploring Biology in Space May See a Slowdown with the End of NASA’s Shuttle Missions
With the last shuttle taking off on July 8, scientists say they won’t have as many opportunities to conduct life sci research.!--h2>
Some talking heads keep saying that the U.S. got very little return on its investment in costly and sometimes disastrous space shuttle missions. Life scientists with experiments aboard the shuttles would argue that point, as many of these studies were impossible to perform in earth’s gravity and have yielded remarkable information.
Regenerative Processes in Microgravity
The Space Tissue Loss program, a collaboration between NASA and the Department of Defense (DoD), sent 20 sets of experiments into space on 18 shuttle launches since March 1992. It is part of the DoD Space Test Program (STP), which uses cell and tissue cultures in microgravity to study its effects on tissue regeneration and wound healing in space.
Eduardo Almeida, Ph.D., the stem cell regeneration program principal investigator and a scientist at NASA’s Ames Research Center, pointed out to GEN that gravity is important for stem cell health. “In its absence, tissue atrophy occurs, and repair does not occur normally.” He described two experiments aboard space shuttles Atlantis and Discovery.
In one experiment he and his colleagues used a model of stem cell development: mouse embryoid bodies that on earth form a sphere containing patches of differentiated cells such as neurons and muscle cells. “Everything went okay on the ground,” he said of the earth-bound controls, “but failed almost completely in space, as the embryoid body cells did not differentiate, failing to express normally 45 out of 52 differentiated tissue markers from mesoderm, endoderm, and ectoderm lineages, and continued to express stem cell markers such as Sox1 and Sox2.”
In another experiment Dr. Almeida’s team tested the ability of keratinocytes (differentiated from stem cells in space) to migrate correctly. Keratinocytes are key cells that participate in wound closure and healing. In space the cells lost nearly half of their migratory capacity, suggesting one cause of lack of efficient wound healing in microgravity.
“For mammalian cells, microgravity is not replicable on the ground,” Dr. Almeida explained. “The only way to do these experiments is to go up.” The inability to do experiments in space “is frustrating because it’s really inefficient to do space biology experiments on earth with inadequate experimental models. A year of NASA spaceflight research is worth 10 years of ground research because of the wealth of unique insights space provides.”
For space travel, he said, the current research highlights the importance of gravity in promoting stem cell regenerative health. “For medicine on earth, this space research makes clear that forces generated by gravity are required to promote normal tissue regenerative processes and teaches us that sometimes we need to step back from things like gravity that we take for granted to understand their fundamental importance for life on earth.”
Tissue Genesis (TGI) has provided science experiments, hardware/payload integration, and adult stem cells in support of the NASA/DoD research collaboration. Tissue Genesis vp and GM, Thomas F. Cannon, told GEN that the company’s core expertise is in space shuttle cell experimentation.
“We were the science/hardware integrators for three experiments flown on the STS-135 DoD Space Test Program manifested Cell Culture Module (CCM),” he said. The CCM is a hollow fiber-based automated perfusion cell culture payload, originally developed at the Walter Reed Army Institute of Research, Cannon explained. It performs a variety of automated injections, collections, and culture manipulations.
Tissue Genesis also participated in a Telemedicine and Advanced Technology Research Center (TATRC), USAMRMC-sponsored experiment that cultured and grew adipose-derived regenerative cells recovered by the TGI Cell Isolation System.
Back at TGI, Joon Paek, Ph.D., the project PI, evaluated the trophic factors and immunomodulatory response of the cells in the space environment. “We have the cells now back in our lab and they are continuing to pump out growth factors. Hopefully we will have some exciting results to report. The two other investigators—Dr. Almeida, and Dr. Rasha Hammamieh, USAMRMC—are reporting very good preliminary results as well.”
Bone and Muscle Loss
Since 2001, Amgen has also been conducting tests in space. Its research has explored three compounds developed to combat bone or muscle loss. Amgen treated mice with osteoprotegerin (OPG) to determine whether the molecule could prevent bone loss when the animals were in zero gravity conditions. Results of the OPG experiment showed that a single, preflight treatment of the mice with Amgen’s OPG prevented bone loss.
The company is developing a myostatin inhibitor known as AMG 745 for muscle wasting disorders. The compound is currently in Phase I studies and is distinct from the molecule used in the 2007 space studies.
In April, Amgen and UCB reported positive results from the Phase II study comparing AMG 785/CDP7851 to placebo in postmenopausal women with low bone mineral density for the treatment of postmenopausal osteoporosis. The study met its primary endpoint, showing increases in lumbar spine bone mineral density at month 12 for the AMG 785/CDP7851 active arms versus the placebo arm. In addition, the drug compared positively with the two active comparators, teriparatide and alendronate.
Changing Protocols for Research
Commenting on the loss of the shuttle missions, Louis Stodieck, director of BioServe Space Technologies, said in Nature that neither the option of using commercial space cargo services such as Space Exploration Technologies’ Dragon or Orbital Sciences’ Cygnus spacecrafts offers a “great option for returning samples.”
So, he added, scientists will have to adapt their research protocols. “Because we will have less ability to bring things back, we will be doing analyses in space and sending the data down, not the samples,” he pointed out.
For scientists who have devoted considerable time and effort devising experiments that take advantage of rocket science to gain insights into biological science, few shots remain for getting studies into space.
Patricia F. Dimond, Ph.D. ([email protected]), is a principal at BioInsight Consulting.
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