期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 29, 期 2, 页码 111-127出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2017.7097
关键词
stem cells; antioxidant gene response; heme; mesenchymal stem cell
资金
- Polish National Science Centre [2013/11/N/NZ3/00958, 2013/11/N/NZ1/02399, 2015/18/NZ3/00387]
- European Union under the European Regional Development Fund Operational Programme Innovative Economy [POIG-01.02.01-109/09]
- National Centre for Research and Development (STRATEGMED) [2/269415/11/NCBR/2015]
- Foundation for Polish Science (FNP)
- Ministry of Science and Higher Education
Aims: Mesenchymal stromal cells (MSCs) are heterogeneous cells from adult tissues that are able to differentiate in vitro into adipocytes, osteoblasts, or chondrocytes. Such cells are widely studied in regenerative medicine. However, the success of cellular therapy depends on the cell survival. Heme oxygenase-1 (HO-1, encoded by the Hmox1 gene), an enzyme converting heme to biliverdin, carbon monoxide, and Fe2+, is cytoprotective and can affect stem cell performance. Therefore, our study aimed at assessing whether Hmox1 is critical for survival and functions of murine bone marrow MSCs. Results: Both MSC Hmox1(+/+) and Hmox1(-/-) showed similar phenotype, differentiation capacities, and production of cytokines or growth factors. Hmox1(+/+) and Hmox1(-/-) cells showed similar survival in response to 50 mu mol/L hemin even in increased glucose concentration, conditions that were unfavorable for Hmox1(-/-) bone marrow-derived proangiogenic cells (BDMC). Hmox1(+/+) MSCs but not fibroblasts retained low ROS levels even after prolonged incubation with 50mol/L hemin, although both cell types have a comparable Hmox1 expression and similarly increase its levels in response to hemin. MSCs Hmox1(-/-) treated with hemin efficiently induced expression of a vast panel of antioxidant genes, especially enzymes of the glutathione pathway. Innovation and Conclusion: Hmox1 overexpression is a popular strategy to enhance viability and performance of MSCs after the transplantation. However, murine MSCs Hmox1(-/-) do not differ from wild-type MSCs in phenotype and functions. MSC Hmox1(-/-) show better resistance to hemin than fibroblasts and BDMCs and rapidly react to the stress by upregulation of quintessential genes in antioxidant response. Antioxid. Redox Signal. 00, 000-000.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据