Hypoxia/Reoxygenation-Preconditioned Human Bone Marrow-Derived Mesenchymal Stromal Cells Rescue Ischemic Rat Cortical Neurons by Enhancing Trophic Factor Release.

Abstract

Bone marrow-derived mesenchymal stromal cells (BM-MSCs) represent a promising tool for stem cell-based therapies. However, the majority of MSCs fail to reach the injury site and have only minimal therapeutic effect. In this study, we assessed whether hypoxia/reoxygenation (H/R) preconditioning of human BM-MSCs could increase their functional capacity and beneficial effect on ischemic rat cortical neurons. Human BM-MSCs were cultured under hypoxia (1% O2) and with long-term reoxygenation for various times to identify the optimal conditions for increasing their viability and proliferation. The effects of H/R preconditioning on the BM-MSCs were assessed by analyzing the expression of prosurvival genes, trophic factors, and cell migration assays. The functionally improved BM-MSCs were cocultured with ischemic rat cortical neurons to compare with normoxic cultured BM-MSCs. Although the cell viability and proliferation of BM-MSCs were reduced after 1 day of hypoxic culture (1% O2), when this was followed by 5-day reoxygenation, the BM-MSCs recovered and multiplied extensively. The immunophenotype and trilineage differentiation of BM-MSCs were also maintained under this H/R preconditioning. In addition, the preconditioning enhanced the expression of prosurvival genes, the messenger RNA (mRNA) levels of various trophic factors and migration capacity. Finally, coculture with the H/R-preconditioned BM-MSCs promoted the survival of ischemic rat cortical neurons. H/R preconditioning of BM-MSCs increases prosurvival signals, trophic factor release, and cell migration and appears to increase their ability to rescue ischemic cortical neurons. This optimized H/R preconditioning procedure could provide the basis for a new strategy for stem cell therapy in ischemic stroke patients.

• Authors: Young Seo Kim, Min Young Noh, Kyung Ah Cho, Hyemi Kim, Min-Soo Kwon, Kyung Suk Kim, Juhan Kim, Seong-Ho Koh, Seung Hyun Kim
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 52 Issue 1 Pg. 792-803 (Aug 2015) ISSN: 1559-1182 [Electronic] United States
• PMID: 25288154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Nerve Growth Factors
• RNA, Messenger
• Oxygen

Topics

• Animals
• Bone Marrow Cells (cytology)
• Brain Ischemia (pathology, therapy)
• Cell Hypoxia (drug effects)
• Cell Movement (drug effects)
• Cells, Cultured
• Humans
• Mesenchymal Stem Cell Transplantation
• Mesenchymal Stem Cells (cytology, drug effects)
• Nerve Growth Factors (genetics, metabolism)
• Neurons (drug effects, metabolism, pathology)
• Oxygen (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Rats, Sprague-Dawley