Human Umbilical Mesenchymal Stem Cells Promote Recovery after Chronic Ischemic Stroke in Rats

• Main Authors: Wen-hsing Chang, 張文馨
• Other Authors: Yu-Show Fu
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/tyeas3

碩士 === 國立陽明大學 === 解剖學及細胞生物學研究所 === 103 === Stroke is a leading cause of death and disability, but despite intensive research only a few treatment options exist. Therefore, many patients suffer from chronic stroke are waiting for therapy. One promising strategy for the treatment of stroke is transplantation of stem cells. We have shown that human umbilical mesenchymal stem cells (HUMSCs) in Wharton's jelly possess stem cell properties. HUMSCs can be easily obtained and processed, compared to embryonic and bone marrow stem cells. We also found that the transformed HUMSCs in the striatum were still viable 4 months after transplantation without the need for immunological suppression, suggesting that HUMSCs might be a good stem cell source for transplantation. We previously transplanted HUMSCs into ischemic brain in 24hr after stroke, and then we showed that HUMSCs were effective on the treatment for acute ischemic stroke. Moreover, in this experiment, we tried to investigate whether HUMSCs could also effective in the treatment for chronic stroke, the stage which has already loss brain mass. In this study, we tested the potential of HUMSCs transplantation on treatment for chronic stroke of rat. Focal cerebral ischemia was induced by middle cerebral artery occlusion and reperfusion (MCAO). Fourteen days after MCAO, two types of HUMSCs were transplanted into the ischemic brain, one is HUMSCs cultured within normoxia condition (20% O2), abbreviated to Normoxia-SC group; another is HUMSCs cultured with hypoxia condition (1% O2), abbreviated to Hypoxia-SC group. To study whether culture HUMSCs in the two different ways could influence the therapy efficiencies. HUMSCs were transplanted into the ischemic brain in two sites, each is 5×105 cells. These transplanted HUMSCs survived in the rat ischemic brain and significantly decreased the infracted brain area. Using magnetic resonance imaging (MRI), we observed that both normoxia-SCs and hypoxia-SCs transplantation prevented infracted cortex from atrophy. Furthermore, the behavioral deficits were significant improved in the rotarod test and the cylinder test. At 56 days post-stroke, the rat brain was dissected and then produced brain section. It showed that both normoxia-SCs and hypoxia-SCs transplantation persevered ischemic cortex; besides, it showed that increased neuronal survival and angiogenesis in peri-infarct region after transplantation; moreover, it showed that decreased inflammation spread from the ischemic region. The most interesting, the transplantations of HUMSCs cultured in the hypoxia condition were better than cultured in the normoxia condition on the treatment for chronic stroke. Both the normoxia stem cells and the hypoxia stem cells were survive in the rat cortex. Underlying therapeutic mechanism was also investigated. Analysis of the human cytokine array reveals that HUMSCs are capable of synthesis human cytokines. MCP-1, CXCL1, MIF, CD54, IGFBP-3, and FGF-1 increased in hypoxia stem cells were more than in normoxia stem cells. We speculate that cytokines released by HUMSCs may be involved in the therapeutic mechanisms studied herein. According to our research, HUMSCs transplantation may provide a new approach to restore chronic stroke disease.