Placenta-Expanded Stromal Cell Therapy in a Rodent Model of Simulated Weightlessness

Cells. 2021 Apr 19;10(4):940. doi: 10.3390/cells10040940.

Abstract

Long duration spaceflight poses potential health risks to astronauts during flight and re-adaptation after return to Earth. There is an emerging need for NASA to provide successful and reliable therapeutics for long duration missions when capability for medical intervention will be limited. Clinically relevant, human placenta-derived therapeutic stromal cells (PLX-PAD) are a promising therapeutic alternative. We found that treatment of adult female mice with PLX-PAD near the onset of simulated weightlessness by hindlimb unloading (HU, 30 d) was well-tolerated and partially mitigated decrements caused by HU. Specifically, PLX-PAD treatment rescued HU-induced thymic atrophy, and mitigated HU-induced changes in percentages of circulating neutrophils, but did not rescue changes in the percentages of lymphocytes, monocytes, natural killer (NK) cells, T-cells and splenic atrophy. Further, PLX-PAD partially mitigated HU effects on the expression of select cytokines in the hippocampus. In contrast, PLX-PAD failed to protect bone and muscle from HU-induced effects, suggesting that the mechanisms which regulate the structure of these mechanosensitive tissues in response to disuse are discrete from those that regulate the immune- and central nervous system (CNS). These findings support the therapeutic potential of placenta-derived stromal cells for select physiological deficits during simulated spaceflight. Multiple countermeasures are likely needed for comprehensive protection from the deleterious effects of prolonged spaceflight.

Keywords: CNS; PLX-PAD cells; bone loss; cell therapy; cytokines; hindlimb unloading; hippocampus; immune system; muscle atrophy; placenta; spaceflight.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Body Weight
  • Cell Proliferation
  • Cell- and Tissue-Based Therapy*
  • Cytokines / metabolism
  • Female
  • Hippocampus / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Neurosecretory Systems / pathology
  • Organ Size
  • Placenta / cytology*
  • Pregnancy
  • Rodentia
  • Stress, Physiological
  • Stromal Cells / cytology
  • Weightlessness*
  • X-Ray Microtomography

Substances

  • Cytokines