Himal Iris, Goyal Umesh, Ta Malancha
Indian Institute of Science Education and Research, Kolkata, West Bengal, India.
Stem Cells Int. 2017;2017:5259849. doi: 10.1155/2017/5259849. Epub 2017 Feb 7.
The efficacy of mesenchymal stem cell (MSC) therapy is currently limited by low retention and poor survival of transplanted cells as demonstrated by clinical studies. This is mainly due to the harsh microenvironment created by oxygen and nutrient deprivation and inflammation at the injured sites. The choice of MSC source could be critical in determining fate and cellular function of MSCs under stress. Our objective here was to investigate the influence of ischemia-like stress on Wharton's jelly MSCs (WJ-MSCs) from human umbilical cord to assess their therapeutic relevance in ischemic diseases. We simulated conditions of ischemia in vitro by culturing WJ-MSCs in 2% oxygen in serum deprived and low glucose medium. Under these conditions, WJ-MSCs retained viable population of greater than 80%. They expressed the characteristic MSC surface antigens at levels comparable to the control WJ-MSCs and were negative for the expression of costimulatory molecules. An upregulation of many ECM and adhesion molecules and growth and angiogenic factors contributing to wound healing and regeneration was noted in the ischemic WJ-MSC population by a PCR array. Their migration ability, however, got impaired. Our findings provide evidence that WJ-MSCs might be therapeutically beneficial and potent in healing wounds under ischemic conditions.
临床研究表明,间充质干细胞(MSC)疗法的疗效目前受到移植细胞低留存率和低存活率的限制。这主要是由于损伤部位因缺氧、营养缺乏和炎症而形成的恶劣微环境所致。在应激状态下,MSC来源的选择对于决定MSC的命运和细胞功能可能至关重要。我们在此的目的是研究缺血样应激对人脐带华通氏胶间充质干细胞(WJ-MSCs)的影响,以评估其在缺血性疾病中的治疗相关性。我们通过在血清缺乏和低糖培养基中于2%氧气条件下培养WJ-MSCs,在体外模拟缺血条件。在这些条件下,WJ-MSCs保持了大于80%的存活细胞群。它们表达的特征性MSC表面抗原水平与对照WJ-MSCs相当,且共刺激分子表达呈阴性。通过PCR阵列发现,缺血的WJ-MSC群体中许多有助于伤口愈合和再生的细胞外基质(ECM)、黏附分子以及生长和血管生成因子上调。然而,它们的迁移能力受损。我们的研究结果证明,WJ-MSCs在缺血条件下的伤口愈合中可能具有治疗益处且效果显著。