Coencapsulation of ISCs and MSCs Enhances Viability and Function of both Cell Types for Improved Wound Healing
Coencapsulation of ISCs and MSCs Enhances Viability and Function of both Cell Types for Improved Wound Healing
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DOI：
10.1007/s12195-019-00582-3
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发表时间：
2019-10-01
影响因子：
2.8
通讯作者：
Olabisi, Ronke M.
中科院分区：
文献类型：
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作者：
Aijaz, Ayesha;Teryek, Matthew;Olabisi, Ronke M.
引言我们以前证明了胰岛素分泌细胞（ISCs）加速慢性伤口的愈合，并且已知间充质干细胞（MSC）也加速伤口愈合。在这里，我们报告了两种细胞类型的组合共封装到合成水凝胶敷料中加速慢性伤口愈合比对照快3倍，比单独递送的每种细胞类型快2倍。具体而言，ISCs释放的胰岛素激活PI3/Akt通路，这对MSC的功能和存活至关重要。MSC反过来又提高了ISCs的活力和功能。材料和方法将MSC和/或大鼠胰岛肿瘤RIN-m细胞包封到聚乙二醇二丙烯酸酯水凝胶片中，并根据Rutgers IACUC批准的方案施加到遗传性糖尿病雄性小鼠（BKS. Cg-m +/+ Leprdb/J）背部上的1cm（2）全层切除伤口。使用活/死活力/细胞毒性试剂盒评估包封的细胞活力。通过ELISA评估Akt磷酸化、胰岛素、VEGF和TGF-β 1分泌。在术后第14天和第28天处死动物，收集伤口组织进行组织学和蛋白质印迹分析。结果ISC：MSC联合组的各项分泌产物及磷酸化Akt水平均最高，创面愈合时间为14 d，ISC组或MSC组创面愈合时间为28 d，对照组创面愈合时间为40 d。此外，ISC：MSC组愈合无中间结痂或瘢痕。结论：MSC与ISCs的组合比单独递送细胞产生更强的愈合反应，从而促进了MSC治疗的共包封的进一步研究。
Introduction We previously demonstrated that insulin secreting cells (ISCs) accelerate healing of chronic wounds, and it is known that mesenchymal stem cells (MSCs) also accelerate wound healing. Here, we report that the combination of both cell types coencapsulated into a synthetic hydrogel dressing accelerates chronic wound healing 3 x faster than control and 2 x faster than each cell type delivered singly. Specifically, insulin released by ISCs activates the PI3/Akt pathway, which is vital to the function and survival of MSCs. MSCs in turn improve the viability and function of ISCs. Materials and Methods MSCs and/or rat islet tumor RIN-m cells were encapsulated into polyethylene glycol diacrylate hydrogel sheets and applied to 1 cm(2) full thickness excisional wounds on the dorsa of genetically diabetic male mice (BKS.Cg-m +/+Leprdb/J) in accordance with protocols approved by the Rutgers IACUC. Encapsulated cell viability was assessed using a LIVE/DEAD Viability/Cytotoxicity Kit. Akt phosphorylation, insulin, VEGF, and TGF-beta 1 secretion were assessed by ELISA. Animals were sacrificed on postoperative days 14 and 28 and wound tissue was collected for histological and western blot analysis. Results ISC:MSC combination groups had the highest levels of every secreted product and phosphorylated Akt, and closed wounds in 14 days, ISC-only or MSC-only groups closed wounds in 28 days, control groups closed wounds in 40 days. Further, ISC:MSC groups healed without intermediate scab or scar. Conclusions Combining MSCs with ISCs results in a more robust healing response than singly delivered cells, warranting further investigation of coencapsulation for MSC therapies.