Hamilton Diana C, Shih Hank H, Schubert Richard A, Michie Sara A, Staats Paul N, Kaplan David L, Fontaine Magali J
Department of Pathology, Stanford University School of Medicine, CA, USA.
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
J Tissue Eng Regen Med. 2017 Mar;11(3):887-895. doi: 10.1002/term.1990. Epub 2015 Jan 26.
The success of pancreatic islet (PI) transplantation is challenged by PI functional damage during the peritransplantation period. A silk-based encapsulation platform including mesenchymal stromal cells (MSCs) was evaluated for islet cell delivery in vivo. Islet equivalents (IEQs) were transplanted into the epididymal fat pads of mice with streptozotocin-induced diabetes. Three PI combinations were tested: (A) co-encapsulated in silk with MSCs; (b) encapsulated in silk alone; or (c) pelleted. Blood glucose levels were monitored and intraperitoneal glucose tolerance test (IPGTT) was performed upon return to euglycaemia. Grafts were removed for histology and cytokine content analysis. Mice with PI grafts in silk showed a prompt return to euglycaemia. IPGTT was significantly improved with PI in silk with MSCs, compared to PI in silk alone or pelleted. Both Th and Th cytokines were increased in PI grafts in silk, but Th cytokines were decreased significantly with PI and MSC co-encapsulation. Histological analysis showed osteogenesis and chondrogenesis in the silk grafts containing MSCs. Future studies will evaluate MSC stability and function in vivo and improve silk biocompatibility for applications in islet transplantation. Copyright © 2015 John Wiley & Sons, Ltd.
胰岛移植的成功受到移植期间胰岛功能损伤的挑战。评估了一种包含间充质基质细胞（MSC）的基于丝的封装平台用于体内胰岛细胞递送。将胰岛当量（IEQ）移植到链脲佐菌素诱导的糖尿病小鼠的附睾脂肪垫中。测试了三种胰岛组合：（A）与MSC共封装在丝中；（b）单独封装在丝中；或（c）制成丸剂。监测血糖水平，并在恢复正常血糖后进行腹腔内葡萄糖耐量试验（IPGTT）。取出移植物进行组织学和细胞因子含量分析。胰岛移植到丝中的小鼠血糖迅速恢复正常。与单独封装在丝中的胰岛或制成丸剂的胰岛相比，与MSC共封装在丝中的胰岛的IPGTT显著改善。丝中的胰岛移植物中Th和Th细胞因子均增加，但胰岛与MSC共封装时Th细胞因子显著降低。组织学分析显示，含有MSC的丝移植物中有成骨和软骨形成。未来的研究将评估MSC在体内的稳定性和功能，并改善丝在胰岛移植应用中的生物相容性。版权所有©2015 John Wiley & Sons, Ltd.
