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从骨髓和脂肪组织来源的犬间充质干细胞中定制生成胰岛素产生细胞。

Tailored generation of insulin producing cells from canine mesenchymal stem cells derived from bone marrow and adipose tissue.

机构信息

Inter-Disciplinary Program of Pharmacology, Graduate School, Chulalongkorn University, Bangkok, Thailand.

Veterinary Pharmacology and Stem Cell Research Laboratory, Veterinary Stem Cell and Bioengineering Innovation Center (VSCBIC), Faculty of Veterinary Science, Chulalongkorn University, Bangkok, Thailand.

出版信息

Sci Rep. 2021 Jun 11;11(1):12409. doi: 10.1038/s41598-021-91774-3.

DOI:10.1038/s41598-021-91774-3
PMID:34117315
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8196068/
Abstract

The trend of regenerative therapy for diabetes in human and veterinary practices has conceptually been proven according to the Edmonton protocol and animal models. Establishing an alternative insulin-producing cell (IPC) resource for further clinical application is a challenging task. This study investigated IPC generation from two practical canine mesenchymal stem cells (cMSCs), canine bone marrow-derived MSCs (cBM-MSCs) and canine adipose-derived MSCs (cAD-MSCs). The results illustrated that cBM-MSCs and cAD-MSCs contain distinct pancreatic differentiation potential and require the tailor-made induction protocols. The effective generation of cBM-MSC-derived IPCs needs the integration of genetic and microenvironment manipulation using a hanging-drop culture of PDX1-transfected cBM-MSCs under a three-step pancreatic induction protocol. However, this protocol is resource- and time-consuming. Another study on cAD-MSC-derived IPC generation found that IPC colonies could be obtained by a low attachment culture under the three-step induction protocol. Further, Notch signaling inhibition during pancreatic endoderm/progenitor induction yielded IPC colonies through the trend of glucose-responsive C-peptide secretion. Thus, this study showed that IPCs could be obtained from cBM-MSCs and cAD-MSCs through different induction techniques. Also, further signaling manipulation studies should be conducted to maximize the protocol's efficiency.

摘要

根据埃德蒙顿方案和动物模型，再生疗法在人类和兽医实践中治疗糖尿病的趋势已得到概念验证。建立用于进一步临床应用的替代胰岛素产生细胞（IPC）资源是一项具有挑战性的任务。本研究从两种实用的犬间充质干细胞（cMSCs），犬骨髓来源的间充质干细胞（cBM-MSCs）和犬脂肪来源的间充质干细胞（cAD-MSCs）中研究了 IPC 的生成。结果表明，cBM-MSCs 和 cAD-MSCs 具有不同的胰腺分化潜力，需要定制的诱导方案。有效生成 cBM-MSC 衍生的 IPC 需要使用 PDX1 转染的 cBM-MSCs 的悬滴培养，结合遗传和微环境操作，在三步胰腺诱导方案下进行。然而，该方案需要大量的资源和时间。另一项关于 cAD-MSC 衍生的 IPC 生成的研究发现，通过三步诱导方案下的低附着培养可以获得 IPC 集落。此外，在胰腺内胚层/祖细胞诱导过程中抑制 Notch 信号通路可通过葡萄糖反应性 C 肽分泌的趋势产生 IPC 集落。因此，本研究表明可以通过不同的诱导技术从 cBM-MSCs 和 cAD-MSCs 获得 IPC。此外，应进行进一步的信号转导操作研究，以最大限度地提高该方案的效率。

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