Wharton's Jelly Mesenchymal Stem Cells as Candidates for Beta Cells Regeneration: Extending the Differentiative and Immunomodulatory Benefits of Adult Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes
Wharton's Jelly Mesenchymal Stem Cells as Candidates for Beta Cells Regeneration: Extending the Differentiative and Immunomodulatory Benefits of Adult Mesenchymal Stem Cells for the Treatment of Type 1 Diabetes
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DOI：
10.1007/s12015-010-9196-4
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发表时间：
2011-06-01
影响因子：
4.8
通讯作者：
La Rocca, Giampiero
中科院分区：
文献类型：
--
作者：
Anzalone, Rita;Lo Iacono, Melania;La Rocca, Giampiero
间充质干细胞（MSC）独特地能够跨越萌发层边界（即能够向外胚层、中胚层和内胚层衍生的细胞型分化），并且被视为用于多种疾病的再生医学方法的有前景的细胞。I型糖尿病治疗应该潜在地受益于这种分化的细胞：通过干细胞分化寻找器官/胰岛移植策略的替代方案是一项正在进行的任务，在大多数实验环境中已经实现了重要的目标（例如胰岛素产生和正常血恢复），尽管仍然需要谨慎以确保体内安全和持久的效果。MSC可以通过离体培养大量获得，并且可以分化为产胰岛素细胞（IPC）。此外，最近的报道证明MSC具有免疫调节活性（作用于先天性和获得性免疫效应物），这应该导致移植细胞的免疫原性降低，从而限制排斥。此外，已经提出MSC施用应当用于减弱导致β细胞破坏的自身免疫过程。本文综述了近年来MSC向IPC分化的研究进展。特别是，我们比较了分化协议的有效性，用于表征分化后代的标志物和功能测定，以及体内对照。我们进一步推测来自人脐带的沃顿氏胶的MSC如何可能代表更有前途的再生医学工具，如最近在人类受试者的内胚层衍生器官（如肝脏）中所证明的，还考虑到其与其他MSC群体相比特有的免疫调节特征。
Mesenchymal stem cells (MSC) are uniquely capable of crossing germinative layers borders (i.e. are able to differentiate towards ectoderm-, mesoderm- and endoderm-derived cytotypes) and are viewed as promising cells for regenerative medicine approaches in several diseases. Type I diabetes therapy should potentially benefit from such differentiated cells: the search for alternatives to organ/islet transplantation strategies via stem cells differentiation is an ongoing task, significant goals having been achieved in most experimental settings (e.g. insulin production and euglycaemia restoration), though caution is still needed to ensure safe and durable effects in vivo. MSC are obtainable in high numbers via ex vivo culture and can be differentiated towards insulin-producing cells (IPC). Moreover, recent reports evidenced that MSC possess immunomodulatory activities (acting on both innate and acquired immunity effectors) which should result in a reduction of the immunogenicity of transplanted cells, thus limiting rejection. Moreover it has been proposed that MSC administration should be used to attenuate the autoimmune processes which lead to the destruction of beta cells. This review illustrates the recent advances made in differentiating human MSC to IPC. In particular, we compare the effectiveness of the differentiation protocols applied, the markers and functional assays used to characterize differentiated progeny, and the in vivo controls. We further speculate on how MSC derived from Wharton's jelly of human umbilical cord may represent a more promising regenerative medicine tool, as recently demonstrated for endoderm-derived organs (as liver) in human subjects, also considering their peculiar immunomodulatory features compared to other MSC populations.