Exploring the direct and delayed effects of microgravity on beta-cell proliferation and effect of long-lasting microgravity on neural crest stem cells (Ax-3)

We previously showed in ground experiments that boundary cap neural crest stem cells (BC) induce insulin-producing β-cell proliferation in pancreatic islets.

After Maser 14 (M14) sounding rocket flight BC proliferation was increased, and genes associated with proliferation and survival were upregulated. Subsequent Maser 15 (M15) experiment confirmed these findings.

During that flight, we examined, in addition, the impact of microgravity (µg) on mouse and human β-cells cultured alone or in combination with BC.

We detected increased β-cell proliferation in islets alone in the µg exposed group and a substantial increase in human β-cell survival in the µg group on day 7 post-flight, but not at earlier stages. This points to a delayed effect of µg.

Furthermore, we found proliferation of mouse islets in 3D printed scaffolds 3 weeks after M15 exposure, specifically in the µg group. We recently collected  BC from Axiom Mission (Ax)-3 experiment with long-lasting µg effect. The started analysis has revealed new properties of these cells, compared to BC with short µg exposure.

We, therefore, in addition, will explore their effect on β-cell proliferation, survival and function. This proposal aims to translate these effects  to ground-based facilities by a simulated µg (s-µg) environment.

The related tests will elucidate (i) if β-cell proliferation can be stimulated in islets alone (mouse and human origin) or combined with BC; (ii) whether these effects are mediated through cell-intrinsic properties or factors secreted during the µg phase; (iii) the extent of delayed µg effects on various combinations of BC, β-cells, and pancreatic islets cultured free-floating, or 3D-printed, using morphological, genetic and physiological methods; (iv) whether these effects can be translated to ground-based medicine with the purpose to accelerate β-cell proliferation rate and thus increase β-cell mass; (v) investigate the BC from Ax-3 by combinatorial metabolomic, genetic, physiological and exosome analysis to elucidate their unique ability to overcome long-lasting µg effect in anaerobic condition and aim to reproduce it on s-µg facilities; (vi) develop islet organoid and explore its potential for implantation into an animal model of type 1 diabetes and for testing in future space experiments.