Reversal of experimental diabetes in mice by transplantation of neo-islets generated from human amnion-derived mesenchymal stromal cells using immuno-isolatory macrocapsules
Reversal of experimental diabetes in mice by transplantation of neo-islets generated from human amnion-derived mesenchymal stromal cells using immuno-isolatory macrocapsules
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DOI：
10.3109/14653249.2010.509546
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发表时间：
2010-12-01
期刊：
影响因子：
4.5
通讯作者：
Bhonde, Ramesh R.
中科院分区：
文献类型：
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作者：
Kadam, Sachin S.;Sudhakar, M.;Bhonde, Ramesh R.
背景目标。当前干细胞来源的伦理和生物学限制导致人们寻求寻找人类来源的多能干细胞的替代来源。羊膜作为再生医学的细胞来源而引起人们的兴趣，因为它易于获得、可塑性强，而且取之不尽、用之不竭，不会违反独立生命的神圣性。尽管研究人员已经展示了人类羊膜上皮细胞的干细胞样潜力，但羊膜间质部分的研究仍然较少。方法。我们建立了源自足月人羊膜的间充质样干细胞的长期培养物，并将其分化为功能性胰腺谱系。结果。羊膜来源的间充质样干细胞表达各种间充质标记物并表现出多向分化能力。我们还观察到，这些细胞在暴露于含有特定生长因子和分化剂的无血清限定培养基时可以形成胰岛样簇（ILC）。通过免疫细胞化学，分化的 ILC 显示人胰岛素、胰高血糖素和生长抑素的表达，而定量逆转录/实时聚合酶链反应 (qRT-PCR) 数据则显示胰岛素、胰高血糖素、生长抑素、Ngn3 和 Isl1 的表达。此外，将ILC封装在聚氨酯-聚乙烯吡咯烷酮大胶囊中并随后将其移植到实验性糖尿病小鼠中导致血糖恢复正常，表明它们能够对高葡萄糖做出反应而不会产生免疫排斥。结论。我们的结果表明，羊膜来源的间充质基质细胞可以进行胰岛新生，表明羊膜可以作为糖尿病细胞替代疗法的替代胰岛来源。
Background aims. The ethical and biologic limitations with current sources of stem cells have resulted in a quest to look for alternative sources of multipotent stem cells of human origin. Amniotic membrane is of interest as a source of cells for regenerative medicine because of its ease of availability, plasticity and inexhaustible source that does not violate the sanctity of independent life. Although researchers have shown the stem cell-like potential of human amniotic epithelial cells, the mesenchymal part of amnion has remained less explored. Methods. We established a long-term culture of mesenchymal-like stem cells derived from full-term human amniotic membrane and their differentiation into functional pancreatic lineage. Results. The amnion-derived mesenchymal-like stem cells expressed various mesenchymal markers and demonstrated multilineage differentiation capacity. We also observed that these cells could form islet-like clusters (ILC) on exposure to serum-free defined media containing specific growth factor and differentiating agents. Differentiated ILC showed expression of human insulin, glucagon and somatostatin by immunocytochemistry, while quantitative reverse transcription/real-time-polymerase chain reaction (qRT-PCR) data demonstrated the expression of insulin, glucagon, somatostatin, Ngn3 and Isl1. Moreover, encapsulation of the ILC in polyurethane-polyvinyl pyrrolidone macrocapsules and their subsequent transplantation in experimental diabetic mice resulted in restoration of normoglycemia, indicating their ability to respond to high glucose without immunorejection. Conclusions. Our results demonstrate that amnion-derived mesenchymal stromal cells can undergo islet neogenesis, indicating amnion as an alternative source of islets for cell replacement therapy in diabetes.