Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells
Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells
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DOI：
10.1634/stemcells.2007-0826
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发表时间：
2008-01-01
期刊：
影响因子：
5.2
通讯作者：
Umezawa, Akihiro
中科院分区：
文献类型：
--
作者：
Hida, Naoko;Nishiyama, Nobuhiro;Umezawa, Akihiro
干细胞治疗可以帮助修复受损的心脏组织。然而，目前鉴定用于人类的许多合适的细胞难以获得并且涉及侵入性程序。在我们寻找比骨髓干细胞具有更高的心肌发生潜力的新型干细胞时，我们发现可以从人类月经血中收获有效的心肌细胞样细胞。这代表了心脏干细胞治疗材料的新的、非侵入性的和有效的来源。我们证明月经血来源的间充质细胞（MMCs）在诱导后开始自发搏动，表现出心肌细胞特异性动作电位。心肌肌钙蛋白I阳性心肌细胞占体外培养的MMCs的27%~ 32%。MMCs平均增殖28代，而不影响心肌转分化能力，并在心肌诱导前表达加塔-4 mRNA。假设MMCs中大部分心肌样细胞来源于离体子宫内膜腺体，我们建立了单克隆子宫内膜腺体来源的间充质细胞（EMCs），其中76%-97%在体外转分化为心肌细胞。EMCs和MMCs均为CD 29、CD 105阳性，CD 34、CD 45阴性。利用一种新的三维EMC细胞片操作将EMC移植到受体心脏上，在体内转分化为心脏组织层。移植的MMC还显著恢复受损的心脏功能，减少裸大鼠模型中的心肌梗死（MI）面积，在体内MI区域观察到MMC衍生的心肌细胞组织。因此，MMCs似乎是一种潜在的新的，容易获得的心脏干细胞为基础的治疗材料来源。
Stem cell therapy can help repair damaged heart tissue. Yet many of the suitable cells currently identified for human use are difficult to obtain and involve invasive procedures. In our search for novel stem cells with a higher cardiomyogenic potential than those available from bone marrow, we discovered that potent cardiac precursor-like cells can be harvested from human menstrual blood. This represents a new, noninvasive, and potent source of cardiac stem cell therapeutic material. We demonstrate that menstrual blood-derived mesenchymal cells (MMCs) began beating spontaneously after induction, exhibiting cardiomyocyte-specific action potentials. Cardiac troponin-I-positive cardiomyocytes accounted for 27%-32% of the MMCs in vitro. The MMCs proliferated, on average, 28 generations without affecting cardiomyogenic transdifferentiation ability, and expressed mRNA of GATA-4 before cardiomyogenic induction. Hypothesizing that the majority of cardiomyogenic cells in MMCs originated from detached uterine endometrial glands, we established monoclonal endometrial gland-derived mesenchymal cells (EMCs), 76%-97% of which transdifferentiated into cardiac cells in vitro. Both EMCs and MMCs were positive for CD29, CD105 and negative for CD34, CD45. EMCs engrafted onto a recipient's heart using a novel 3-dimensional EMC cell sheet manipulation transdifferentiated into cardiac tissue layer in vivo. Transplanted MMCs also significantly restored impaired cardiac function, decreasing the myocardial infarction (MI) area in the nude rat model, with tissue of MMC-derived cardiomyocytes observed in the MI area in vivo. Thus, MMCs appear to be a potential novel, easily accessible source of material for cardiac stem cell-based therapy.