Amniotic Mesenchymal Stem Cells Enhance Wound Healing in Diabetic NOD/SCID Mice through High Angiogenic and Engraftment Capabilities

Abstract

Although human amniotic mesenchymal stem cells (AMMs) have been recognised as a promising stem cell resource, their therapeutic potential for wound healing has not been widely investigated. In this study, we evaluated the therapeutic potential of AMMs using a diabetic mouse wound model. Quantitative real-time PCR and ELISA results revealed that the angiogenic factors, IGF-1, EGF and IL-8 were markedly upregulated in AMMs when compared with adipose-derived mesenchymal stem cells (ADMs) and dermal fibroblasts. In vitro scratch wound assays also showed that AMM-derived conditioned media (CM) significantly accelerated wound closure. Diabetic mice were generated using streptozotocin and wounds were created by skin excision, followed by AMM transplantation. AMM transplantation significantly promoted wound healing and increased re-epithelialization and cellularity. Notably, transplanted AMMs exhibited high engraftment rates and expressed keratinocyte-specific proteins and cytokeratin in the wound area, indicating a direct contribution to cutaneous closure. Taken together, these data suggest that AMMs possess considerable therapeutic potential for chronic wounds through the secretion of angiogenic factors and enhanced engraftment/differentiation capabilities.

Mesenchymal Stem Cell Therapy in Type 1 Diabetes Mellitus and Its Main Complications: From Experimental Findings to Clinical Practice

“…Wounds treated with MSCs in these reports have shown a qualitative improvement regarding histological characteristics, such as superior rete ridge architecture, multi-layered structure, improved dermalepidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [120][121][122][123].…”

“…MSCs have been used to date in treating different skin disorders [20,118,119]; several groups have reported successful wound healing in pre-clinical models of diabetic wounds after the administration of autologous or allogeneic MSCs from different sources [120][121][122][123]. Wounds treated with MSCs in these reports have shown a qualitative improvement regarding histological characteristics, such as superior rete ridge architecture, multi-layered structure, improved dermalepidermal junction and the formation of new skin appendage structures, such as hair follicles and sebaceous glands [120][121][122][123].…”

Stem Cells in Skin Wound Healing: Are We There Yet?

“…hASCs-CM is shown to promote the synthesis of collagen I by DFbs, 55,59,60 thus influencing wound closure. This effect on DFbs was also observed when human amniotic fluid MSCs-CM 61,62 was administrated in a mouse excisional wound, suggesting their action via the transforming growth factor beta (TGF-b)/SMAD2 pathway. 62 Overall, these data demonstrate that MSCs from different sources have a potent secretome that is capable of influencing different cells involved in the wound-healing process, modulating their activation, migration, and proliferation.…”

Aristolochia bracteolata Enhances Wound Healing in vitro through Anti-inflammatory and Proliferative Effect on Human Dermal Fibroblasts and Keratinocytes

“…20 Any growth factor that stimulates cell migration may help to generate an optimized therapeutic protocol for improved wound healing because cell migration is a crucial event in cutaneous wound healing. 21 Consequently, as an in vitro analysis of skin cell behavior, scratch wound assay using HDF were performed. Results showed that A. bracteolata increased the rate of fibroblast wound closure compared with control at 48h.…”