Efficient Induction of Pluripotent Stem Cells from Menstrual Blood
Efficient Induction of Pluripotent Stem Cells from Menstrual Blood
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从经血中高效诱导多能干细胞
DOI：
10.1089/scd.2012.0428
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发表时间：
2013-04-01
影响因子：
4
通讯作者：
Tan, Jichun
中科院分区：
文献类型：
--
作者：
Li, Yang;Li, Xiaoni;Tan, Jichun
将人类体细胞重新编程为多能性的技术允许生产患者特异性诱导多能干细胞（iPSCs），并为再生医学带来了巨大的希望。选择最合适的细胞类型进行诱导，降低病毒转基因激活尤其是致癌基因激活的风险，对iPSC研究具有重要意义。迄今为止，人类真皮成纤维细胞（HDFs）是用于iPSC生成的最常见的细胞来源，但它们有一些局限性。必须进行侵入性皮肤活检以获得HDFs，并且HDFs必须长时间培养才能用于实验。因此，为了开发一种合适的iPSC研究来源，以避免上述局限性，我们在这里确定了来自经血（MenSCs）的基质细胞作为合适的候选者。在本研究中，我们发现通过强力霉素诱导的慢病毒转导OCT4、SOX2和KLF4， MenSCs可以被重编程为多能状态。此外，我们发现MenSCs的重编程效率明显高于HDFs。OCT4和SOX2的结合足以在不使用c-MYC或KLF4的情况下将MenSCs重编程为iPSCs。由此产生的MenSC-iPSCs在形态、多能标记物、基因表达和多能细胞特异性基因的表观遗传状态方面表现出与人胚胎干细胞相同的特征。这些细胞在体外和体内均能分化为所有3种胚层的各种细胞类型。因此，MenSCs可能是生成iPSCs的首选候选者。
The technology to reprogram human somatic cells back to pluripotency allows the production of patient-specific induced pluripotent stem cells (iPSCs) and holds a great promise for regenerative medicine. Choosing the most suitable cell type for induction and reducing the risk of viral transgene activation, especially oncogene activation, are important for iPSC research. To date, human dermal fibroblasts (HDFs) are the most frequent cell source used for iPSC generation, but they have several limitations. An invasive skin biopsy must be performed to obtain HDFs, and HDFs must be cultured for a prolonged period before they can be used for experiments. Thus, in an effort to develop a suitable source for iPSC studies to avoid the limitations mentioned above, we have here identified stromal cells derived from menstrual blood (MenSCs) as suitable candidates. In the present study, we found that MenSCs can be reprogrammed to pluripotent status by doxycycline-inducible lentiviral transduction of OCT4, SOX2, and KLF4. Additionally, we found that MenSCs have a significantly higher reprogramming efficiency than HDFs. The combination of OCT4 and SOX2 is sufficient to reprogram MenSCs into iPSCs without the use of c-MYC or KLF4. The resulting MenSC-iPSCs showed the same characteristics as human embryonic stem cells with regard to morphology, pluripotent markers, gene expression, and the epigenetic status of pluripotent-cell-specific genes. These cells were able to differentiate into various cell types of all 3 germ layers both in vitro and in vivo. Therefore, MenSCs may be a preferred candidate for generation of iPSCs.