用于递送诱导多能干细胞来源的胰岛素分泌细胞的皮下移植平台的建立。

Establishment of subcutaneous transplantation platform for delivering induced pluripotent stem cell-derived insulin-producing cells.

作者信息

Tran Hong Thuan, Rodprasert Watchareewan, Padeta Irma, Oontawee Saranyou, Purbantoro Steven Dwi, Thongsit Anatcha, Siriarchavatana Parkpoom, Srisuwatanasagul Sayamon, Egusa Hiroshi, Osathanon Thanaphum, Sawangmake Chenphop

机构信息

Second Century Fund (C2F) Chulalongkorn University for Doctoral Scholarship, Chulalongkorn University, Bangkok, Thailand.

Faculty of Veterinary Science, The International Graduate Program of Veterinary Science and Technology (VST), Chulalongkorn University, Bangkok, Thailand.

出版信息

PLoS One. 2025 Jan 30;20(1):e0318204. doi: 10.1371/journal.pone.0318204. eCollection 2025.

Abstract

Potential trend of regenerative treatment for type I diabetes has been introduced for more than a decade. However, the technologies regarding insulin-producing cell (IPC) production and transplantation are still being developed. Here, we propose the potential IPC production protocol employing mouse gingival fibroblast-derived induced pluripotent stem cells (mGF-iPSCs) as a resource and the pre-clinical approved subcutaneous IPC transplantation platform for further clinical confirmation study. With a multi-step induction protocol, the functional and matured IPCs were generated by 13 days with a long-term survival capability. Further double encapsulation of mGF-iPSC-derived IPCs (mGF-iPSC-IPCs) could preserve the insulin secretion capacity and the transplantation potential of the generated IPCs. To address the potential on IPC transplantation, a 2-step subcutaneous transplantation procedure was established, comprising 1) vascularized subcutaneous pocket formation and 2) encapsulated IPC bead transplantation. The in vivo testing confirmed the safety and efficiency of the platform along with less inflammatory response which may help minimize tissue reaction and graft rejection. Further preliminary in vivo testing on subcutaneous IPC-bead transplantation in an induced type I diabetic mouse model showed beneficial trends on blood glucose control and survival rate sustainability of diabetic mice. Taken together, an established mGF-iPSC-IPC generation protocol in this study will be the potential backbone for developing the iPSC-derived IPC production employing human and animal cell resources. As well as the potential further development of IPC transplantation platform for diabetes treatment in human and veterinary practices using an established subcutaneous encapsulated IPC-bead transplantation platform presented in this study.

摘要

十多年来,I型糖尿病再生治疗的潜在趋势已被引入。然而,关于胰岛素产生细胞(IPC)生产和移植的技术仍在开发中。在此,我们提出了一种潜在的IPC生产方案,采用小鼠牙龈成纤维细胞衍生的诱导多能干细胞(mGF-iPSCs)作为资源,并建立了临床前批准的皮下IPC移植平台,用于进一步的临床验证研究。通过多步骤诱导方案,在13天内生成了具有长期存活能力的功能性成熟IPC。对mGF-iPSC衍生的IPC(mGF-iPSC-IPCs)进行进一步的双重封装,可以保留所生成IPC的胰岛素分泌能力和移植潜力。为了解决IPC移植的潜力问题,建立了两步皮下移植程序,包括1)形成血管化皮下囊袋和2)移植封装的IPC珠。体内测试证实了该平台的安全性和有效性,以及较少的炎症反应,这可能有助于最小化组织反应和移植物排斥。在诱导的I型糖尿病小鼠模型中对皮下IPC珠移植进行的进一步初步体内测试显示,对糖尿病小鼠的血糖控制和存活率可持续性有有益趋势。综上所述,本研究中建立的mGF-iPSC-IPC生成方案将成为利用人类和动物细胞资源开发iPSC衍生IPC生产的潜在支柱。同时,利用本研究中建立的皮下封装IPC珠移植平台,在人类和兽医实践中进一步开发用于糖尿病治疗的IPC移植平台也具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5697/11781742/ba9c76f26811/pone.0318204.g001.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索