Human Adipose Mesenchymal Stromal Cells growing into PCL-nHA electrospun scaffolds undergo hypoxia adaptive ultrastructural changes

FRONTINI LOPEZ, Y. R.; RIVERA, L.; ALDANA, ANA AGUSTINA; RIVERO GUADALUPE; LIVERANI, LILIANA; ABRAHAM, GUSTAVO A.; BOCCACCINI, A.R.; BUSTOS, DIEGO M.; UHART, M.

Biotechnology Journal

Wiley

Año: 2023 vol. 18

hAD-MSCs have great potential for tissue regeneration. Since transplanted MSCs are likely to be placed in a hypoxic environment, culturing the cells under hypoxic conditions might improve their post-transplantation survival and regenerative performance. The combination of hAD-MSCs and PCL-nHA nanofibers synergically improves the contribution of both components for osteoblast differentiation. In this work, we hypothesized that this biomaterial constitutes a hypoxic environment for hAD-MSCs. We studied the cellular re-arrangement and the subcellular ultrastructure by TEM of hAD-MSCs grown on PCL-nHA nanofibers, and we compared them with the same cells grown in 2D cultures, over tissue culture-treated plastic, or glass coverslips. Among the most evident changes, PCL-nHA grown cells showed enlarged mitochondria, and accumulation of glycogen granules, consistent with a hypoxic environment. We observed a 3,5 upregulation (p = 0.0379) of HIF-1A gene expression in PCL-nHA grown cells. This work evidences for the first time intra-cellular changes in 3D compared to 2D cultures, which are adaptive responses of the cells to an environment more closely resembling that of the in vivo niche after transplantation, thus PCL-nHA nanofibers are adequate for hAD-MSCs pre-conditioning.