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源自人月经血间充质细胞的新型心脏前体细胞样细胞。

Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells.

作者信息

Hida Naoko, Nishiyama Nobuhiro, Miyoshi Shunichiro, Kira Shinichiro, Segawa Kaoru, Uyama Taro, Mori Taisuke, Miyado Kenji, Ikegami Yukinori, Cui ChangHao, Kiyono Tohru, Kyo Satoru, Shimizu Tatsuya, Okano Teruo, Sakamoto Michiie, Ogawa Satoshi, Umezawa Akihiro

机构信息

Department of Cardiology, Keio University School of Medicine, 35-Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

出版信息

Stem Cells. 2008 Jul;26(7):1695-704. doi: 10.1634/stemcells.2007-0826. Epub 2008 Apr 17.

Abstract

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.

摘要

干细胞疗法有助于修复受损的心脏组织。然而,目前已确定的许多适用于人类的细胞难以获取,且涉及侵入性操作。在我们寻找比骨髓来源的细胞具有更高心肌生成潜力的新型干细胞的过程中,我们发现可以从人类月经血中获取强大的心脏前体细胞样细胞。这代表了一种新的、非侵入性的且强大的心脏干细胞治疗材料来源。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。体外培养时,心肌肌钙蛋白I阳性的心肌细胞占MMCs的27%-32%。MMCs平均增殖28代,且不影响其心肌生成转分化能力,在心肌生成诱导前表达GATA-4的mRNA。由于推测MMCs中的大多数心肌生成细胞起源于脱离的子宫内膜腺体,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%在体外转分化为心脏细胞。EMCs和MMCs的CD29、CD105呈阳性,CD34、CD45呈阴性。使用一种新型的三维EMC细胞片操作将EMCs移植到受体心脏上,它们在体内转分化为心脏组织层。移植的MMCs也显著恢复了受损的心脏功能,减少了裸鼠模型中的心肌梗死(MI)面积,在体内MI区域观察到了MMC来源的心肌细胞组织。因此,MMCs似乎是基于心脏干细胞治疗的一种潜在的新型、易于获取的材料来源。

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