Coencapsulation of ISCs and MSCs Enhances Viability and Function of both Cell Types for Improved Wound Healing

Abstract

IntroductionWe 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 × faster than control and 2 × 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 MethodsMSCs and/or rat islet tumor RIN-m cells were encapsulated into polyethylene glycol diacrylate hydrogel sheets and applied to 1 cm2 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-β1 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.ResultsISC: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.ConclusionsCombining MSCs with ISCs results in a more robust healing response than singly delivered cells, warranting further investigation of coencapsulation for MSC therapies.

Extracellular vesicle‐carried microRNA‐27b derived from mesenchymal stem cells accelerates cutaneous wound healing via E3 ubiquitin ligase ITCH

“…33,34 The ability of MSCs to enhance wound healing has been highlighted in existing literature. 35 Hence, we hypothesized that the transfer of Our initial observations revealed that miR-27b was poorly expressed in the cutaneous wounds of mice with low healing ability. A previous study reported that miR-27b is down-regulated in burned skin.…”

“…Unfavourable wound healing poses a significant threat to public health with an urgent need for fresh novel targets aimed at managing and treating the complications of unfavourable wound healing outcomes 33,34 . The ability of MSCs to enhance wound healing has been highlighted in existing literature 35 . Hence, we hypothesized that the transfer of miR‐27b by MSC‐derived EVs could play a critical role in cutaneous wound healing via the regulation of downstream factors.…”

Mesenchymal stem cell therapy in diabetic foot ulcer: An updated comprehensive review

“…In this research, an enhanced influence on the neovascularization of diabetes wounds was seen, and the epidermis of the cured diabetic lesion was revealed to be thicker as well as more discriminated than the epidermis of the diabetic lesion that had received no therapy 221 . An additional investigation found that using a PEGDA hydrogel to encapsulate a combination of human BM‐MSCs and rat insulin‐secreting cells enhanced diabetic wound repair approximately three times quicker than in the control groups 222 …”

Scaffold-based delivery of mesenchymal stromal cells to diabetic wounds

“…The results showed that both cell delivery methods improved wound healing rate, with a significant difference observed from 7–9 days after treatment, and the cells delivered by the hydrogel group showed similar healing kinetics compared to the direct injection group [ 72 ]. Another study reported that encapsulating a mixture of human BM-MSCs and rat insulin secreting cells (ISCs) in a PEGDA hydrogel promoted diabetic wound healing almost 3 times faster than control group (14 vs. ~ 40 days), without intermediate scab or scar, through increased secretion of insulin, VEGF, TGF-β1 and the viability and function of MSC improved due to activation of the PI3K-Akt/PKB pathway [ 73 ]. This observation suggests that a combination of different cell types may further enhance the therapeutic effects in the diabetic wound.…”