Hypoxia Modulates Regenerative Potential of Fetal Stem Cells.

Yixuan Amy Pei,Ming Pei

doi:10.3390/app12010363

Abstract

Adult mesenchymal stem cells (MSCs) are prone to senescence, which limits the scope of their use in tissue engineering and regeneration and increases the likelihood of post-implantation failure. As a robust alternative cell source, fetal stem cells can prevent an immune reaction and senescence. However, few studies use this cell type. In this study, we sought to characterize fetal cells' regenerative potential in hypoxic conditions. Specifically, we examined whether hypoxic exposure during the expansion and differentiation phases would affect human fetal nucleus pulposus cell (NPC) and fetal synovium-derived stem cell (SDSC) plasticity and three-lineage differentiation potential. We concluded that fetal NPCs represent the most promising cell source for chondrogenic differentiation, as they are more responsive and display stronger phenotypic stability, particularly when expanded and differentiated in hypoxic conditions. Fetal SDSCs have less potential for chondrogenic differentiation compared to their adult counterpart. This study also indicated that fetal SDSCs exhibit a discrepancy in adipogenic and osteogenic differentiation in response to hypoxia.

Highlights

Adult mesenchymal stem cells (MSCs) are a potential solution for cell-based tissue engineering and regeneration due to their self-regenerative capacity and potential to differentiate into a multitude of cell types [1]
Despite no significant differences in cell morphology between nucleus pulposus cell (NPC) and synovium-derived stem cell (SDSC) during expansion (Figure 2A), RT-qPCR data showed a discrepancy in stemness gene expressions of these two human fetal cells and their response to hypoxia (Figure 2B)
We found that hypoxia decreased gene expression of the osteogenic marker BGLAP but increased SP7 in both fetal cell types as well as decreased SPP1 of NPCs and RUNX2 in SDSCs (Figure 6A)

Summary

Introduction

Adult mesenchymal stem cells (MSCs) are a potential solution for cell-based tissue engineering and regeneration due to their self-regenerative capacity and potential to differentiate into a multitude of cell types [1]. A large quantity of autologous adult stem cells is required for tissue engineering—a process that necessitates long-term ex vivo expansion, which can cause cell senescence, resulting in lowered plasticity and limited proliferation capacity [2] These challenges restrict the clinical application of adult MSCs despite their well-characterized properties [3]. In comparison to adult MSCs, fetal MSCs have greater differentiation potential, lower immunogenicity, longer telomeres, and increased intrinsic homing and engraftment ability [4,5] Despite their immense potential for regenerative medicine, given ethical concerns [6], there exists limited knowledge regarding the regenerative potential of fetal MSCs and their responses to external environment stimulation, which have been wellcharacterized in adult MSCs, such as decellularized extracellular matrix (dECM) [7], hypoxia, and soluble factors such as basic fibroblast growth factor [8,9]. There are few articles investigating the influence of hypoxia on the regenerative potential of fetal stem cells despite the importance of hypoxia in adult stem cell differentiation [12]

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