인간 골수유래 중간엽줄기세포의 효능을 높이기 위한 실험적 전처리 전략

Abstract

Background: Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent a promising implement for stem cell-based therapies. Embryonic stem cell (ESC) or Induced pluripotent stem cells (iPSCs) have several limitations for clinical application because of their ethical and safety issues, however, MSCs have no ethical problem and tolerable for safety issue for clinical trials. In this study, we evaluated experimental preconditioning strategy using hypoxic model to enhance the therapeutic efficacy of human BM-MSCs.

Methods: In order to identify ideal condition in increasing cell viability and proliferation, human BM-MSCs were cultured in periods of hypoxia (1% O2) and then reoxygenated for a long-term. An analysis of the expression of prosurvival genes, trophic factors, inflammation cytokines and, cell migration evaluated the effects of hypoxia/reoxygenation (H/R) preconditioning on the BM-MSCs. Ischemic rat cortical neurons were cocultured with the functionally enhanced BM-MSCs.

Results: Even though the cell viability and proliferation of BM-MSCs were decreased after 1day of hypoxia culture (1% O2), the BM-MSCs recovered and multiplied significantly after 5days of reoxygenation. Moreover, in a period of H/R preconditioning (5 days reoxygenation), the immunophenotype and trilineage differentiation of BM-MSCs were maintained, and the expression of prosurvival genes, the mRNA levels of various trophic factors, inflammation cytokines and migration capacity were improved. Eventually, co-culture with H/R preconditioned BM-MSCs advanced the survival of ischemic rat cortical neurons.

Conclusions: In a condition of H/R preconditioning, the prosurvival signals, trophic factor release inflammation cytokines and cell migration of BM-MSCs are increased, which eventually rescue cortical neurons. To improve stem cell therapy, the experiment of H.R preconditioning could provide the basis of a new strategy.