干 细 胞 总 论教学提纲.ppt

Recently, we have turned our attention to the ability of hMSCs to engraft and differentiate in the adult heart. hMSCs were introduced into the hearts of immunodeficient mice through the coronary circulation and found that a percentage of the hMSCs would engraft as single cells surrounded by healthy host cardiomyocytes. The hMSCs persisted for at least 2 months. Over time, the morphology of the implanted hMSCs became indistinguishable from the surrounding cardiomyocytes, and they began to express the proteins specific for striated muscle, including desmin, á-myosin heavy chain, á-actinin, and phospholamban, myosin heavy chain, connexin 43 at levels that were the same as the host cardiomyocytes. But not myo D suggesting the cells were not differentiating to a skeletal myocyte but rather to a cardiac myocyte. 国外成功地采用无血清培养系统体外扩增造血干细胞，特别是脐血造血干细胞。进入了临床的实际应用。美国Colorado大学医院（Colorado University Hospital，CUH）BMT中心的Dr Shpall已应用体外扩增的CBSC治疗41例白血病和恶性肿瘤。不仅全部植活，而且HSC植活时间明显缩短。HSC移植后，不用G-CSF，WBC恢复达到 500/ul和不输血小板，血小板达到 2 x 104/ul的时间在8-11天。 一个非常关键的问题是：细胞因子刺激体外扩增的HSC实际上大部分为HPC。是否存在保持自我更新能力的原始HSC？为此这种体外扩增的HSC/HPC移植的远期疗效受到质疑。 MSC是BM中另一类具有分裂增殖、分化形成多种间质细胞潜能的细胞， 具有多能干细胞的生物学性质（self renewal, proliferation, differentiation） 占BM-MNC 1 /105 - 106 MSC体外培养形态: mono-layer, fibroblast-like, uni-direction 不具有血细胞标记，而具有MSC自身特异表面标记蛋白如SH2、SH3、SH4、 CD13、CD90、CD106 CD34-, HLA-DR-等。BM中MSC和HSC之间的胞体接触，以及MSC分泌的多种细胞因子为HSC分裂、增殖、分化、正常造血提供了合适的微环境。  骨髓间质干细胞 （mesenchymal stem cells，MSCs） hMSCs were isolated from bone marrow and expanded ex vivo. Flow cytometry using many different surface markers has demonstrated the expanded population to be 98% homogeneous BM-MSC cell surface markers 100bp 200bp 300bp 400bp 500bp 600bp M b2MG SCF Flt3 TPO LIF IL-6 IL-11 GM-CSF G-CSF IL-3 Cytokines expression pattern in normal BM-MSCs Note: Cytokines expression pattern in BM-MSCs of patients with MM and AL is as same as that of normal BM-MSC 100bp