ASGSB 1999 Annual Meeting Abstracts

THE EFFECTS OF MICROGRAVITY ON THE EXPRESSION OF A FOREIGN PROTEIN IN TISSUE-ENGINEERED SKELETAL MUSCLE. P.H.U. Lee, H.H. Vandenburgh. Dept of Pathobiology, Brown Univ. School of Medicine, Providence, RI.

It is well known that space flight causes significant muscle atrophy in both humans and animals. Ground-based studies indicate that this atrophy may be due to both indirect effects such as a reduction in the circulating level of growth hormone (GH), or to direct cellular level effects on the muscle fibers. Tissue-engineered bioartificial muscles have been developed to study the direct effects of space flight on skeletal muscle atrophy and have flown on two previous space shuttle missions. The results demonstrate a reduction in muscle protein synthesis leading to myofiber atrophy as a direct result of microgravity (FASEB J. 13, 1031; 1999). Cells genetically engineered to secrete anabolic factors such as growth hormone or insulin-like growth factor-1 can be used in vivo as a cell-based delivery platform and has potential use as a countermeasure for muscle atrophy. It was hypothesized that one complication of cell based gene therapy as a countermeasure in microgravity conditions would be reduced expression of the foreign protein due to a down regulation of protein synthesis. Avian myoblasts were genetically modified to express human recombinant GH (rhGH) and flown aboard the space shuttle on flight STS-95 for nine days in the Dual Materials Dispersion Apparatus (DMDA) from Instrumentation Technology Associates. The DMDA contained 3 flight samples and were maintained at 20C without active perfusion from 5 days pre-flight until 1 day post-flight (total 15 days). Total secretion of rhGH was decreased by 48% (p=0.025) in flight samples relative to ground controls. The results provide valuable information concerning the expression of a foreign protein in microgravity and the potential use of gene therapy methods for preventing skeletal muscle wasting during space travel.

(Supported by NASA grant NAG2-1205)

Back to Meeting Program