Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow nonhematopoietic cells to differentiate into cardiomyocytes
Cardiac stem cells in brown adipose tissue express CD133 and induce bone marrow nonhematopoietic cells to differentiate into cardiomyocytes
复制标题
DOI：
10.1634/stemcells.2006-0588
复制
发表时间：
2007-01-01
期刊：
影响因子：
5.2
通讯作者：
Takakura, Nobuyuki
中科院分区：
文献类型：
--
作者：
Yamada, Yoshihiro;Yokoyama, Shin-Ichiro;Takakura, Nobuyuki
最近，在心脏再生治疗领域取得了值得注意的进展。我们以前报道过棕色脂肪组织（BAT）含有与受损心肌再生相关的心脏祖细胞。在这项研究中，我们发现，CD 133阳性，但不是c-Kit-或Sca-1阳性，细胞分化成心肌细胞（CM）的BAT与高频率。此外，我们发现CD 133（+）棕色脂肪组织来源的细胞（BATDC）可以有效地诱导骨髓细胞（BMCs）向CM分化。骨髓基质细胞被认为具有最大的潜力作为CM的来源，并且两种类型的干细胞群体，MSC和造血干细胞（HSC），已被报道分化为CM;然而，尚未确定哪种群体是CM的更好来源。在这里，我们表明，CD 133阳性的BATDC诱导骨髓基质细胞进入CM，而不是通过细胞融合，但通过二价阳离子介导的细胞与细胞接触时，共培养。此外，由BATDC诱导的BMC能够在体内梗死模型中充当CM补充。最后，我们发现，当与BATDC共培养时，CD 45（-）CD 31（-）CD 105（+）非造血细胞产生的CM数量是lin（-）c-Kit（+）HSC的20倍以上。总之，这些数据表明，CD 133阳性BATDC是CM诱导剂的有用工具，也是CM的来源，骨髓中的非造血成分也是CM的主要来源。
Recently, there has been noteworthy progress in the field of cardiac regeneration therapy. We previously reported that brown adipose tissue ( BAT) contained cardiac progenitor cells that were relevant to the regeneration of damaged myocardium. In this study, we found that CD133-positive, but not c-Kit- or Sca-1-positive, cells in BAT differentiated into cardiomyocytes (CMs) with a high frequency. Moreover, we found that CD133(+) brown adipose tissue-derived cells (BATDCs) effectively induced bone marrow cells (BMCs) into CMs. BMCs are considered to have the greatest potential as a source of CMs, and two sorts of stem cell populations, the MSCs and hematopoietic stem cells (HSCs), have been reported to differentiate into CMs; however, it has not been determined which population is a better source of CMs. Here we show that CD133-positive BATDCs induce BMCs into CMs, not through cell fusion but through bivalent cation-mediated cell-to-cell contact when cocultured. Moreover, BMCs induced by BATDCs are able to act as CM repletion in an in vivo infarction model. Finally, we found that CD45(-)CD31(-)CD105(+) nonhematopoietic cells, when cocultured with BATDCs, generated more than 20 times the number of CMs compared with lin(-)c-Kit(+) HSCs. Taken together, these data suggest that CD133-positive BATDCs are a useful tool as CM inducers, as well as a source of CMs, and that the nonhematopoietic fraction in bone marrow is also a major source of CMs.