1 Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University , Kraków, Poland .
2 Department of Animal Production, College of Agriculture, University of Duhok , Duhok, Iraq .
Antioxid Redox Signal. 2018 Jul 10;29(2):111-127. doi: 10.1089/ars.2017.7097. Epub 2018 Jan 3.
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 Fe, 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.
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 μmol/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 50 μmol/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.
间充质基质细胞（MSCs）是来自成体组织的异质性细胞，能够在体外分化为脂肪细胞、成骨细胞或软骨细胞。这些细胞在再生医学中得到了广泛的研究。然而，细胞治疗的成功取决于细胞的存活率。血红素加氧酶-1（HO-1，由 Hmox1 基因编码），一种将血红素转化为胆红素、一氧化碳和 Fe 的酶，具有细胞保护作用，并能影响干细胞的性能。因此，我们的研究旨在评估 Hmox1 是否对鼠骨髓间充质基质细胞的存活和功能至关重要。
MSC Hmox1 和 Hmox1 均表现出相似的表型、分化能力以及细胞因子或生长因子的产生。即使在高葡萄糖浓度下，Hmox1 和 Hmox1 细胞对 50μmol/L 血红素的反应相似，这对 Hmox1 骨髓来源的促血管生成细胞（BDMC）不利，但它们的存活率相似。即使在与 50μmol/L 血红素长时间孵育后，Hmox1 MSC 也能保持较低的 ROS 水平，而成纤维细胞则不能，尽管这两种细胞类型的 Hmox1 表达相似，并且对血红素的反应相似，都能增加其水平。用血红素处理的 Hmox1 MSC 能有效地诱导大量抗氧化基因的表达，特别是谷胱甘肽途径的酶。创新与结论：HO-1 的过表达是一种提高移植后 MSC 活力和性能的常用策略。然而，鼠 MSCs Hmox1 在表型和功能上与野生型 MSCs 没有差异。MSC Hmox1 对血红素的抵抗力比成纤维细胞和 BDMC 更强，并且通过上调抗氧化反应中的关键基因对压力迅速做出反应。抗氧化。氧化还原信号。00，000-000。
