Mesenchymal Stem Cells for Chronic Wound Healing: Current Status of Preclinical and Clinical Studies

Abstract

Healing skin wounds with anatomic and functional integrity, especially under chronic pathological conditions, remain an enormous challenge. Due to their outstanding regenerative potential, mesenchymal stem cells (MSCs) have been explored in many studies to determine the healing ability for difficult-to-treat diseases. In this article, we review current animal studies and clinical trials of MSC-based therapy for chronic wounds, and discuss major challenges that confront future clinical applications. We found that a wealth of animal studies have revealed the versatile roles and the benefits of MSCs for chronic wound healing. MSC treatment results in enhanced angiogenesis, facilitated reepithelialization, improved granulation, and accelerated wound closure. There are some evidences of the transdifferentiation of MSCs into skin cells. However, the healing effect of MSCs depends primarily on their paracrine actions, which alleviate the harsh microenvironment of chronic wounds and regulate local cellular responses. Consistent with the findings of preclinical studies, some clinical trials have shown improved wound healing after transplantation of MSCs in chronic wounds, mainly lower extremity ulcers, pressure sores, and radiation burns. However, there are some limitations in these clinical trials, especially a small number of patients and imperfect methodology. Therefore, to better define the safety and efficiency of MSC-based wound therapy, large-scale controlled multicenter trials are needed in the future. In addition, to build a robust pool of clinical evidence, standardized protocols, especially the cultivation and quality control of MSCs, are recommended. Altogether, based on current data, MSC-based therapy represents a promising treatment option for chronic wounds.

Efficacy of topical and systemic transplantation of mesenchymal stem cells in a rat model of diabetic ischemic wounds

“…Many previous studies and clinical trials have shown that stem cells therapy and related biotechnology hold a great promise in regenerative medicine applications [25][26][27][28]. BM-MSCs, adipose-derived mesenchymal stem cells (AD-MSCs), and stromal vascular fraction cells (SVFs) have the ability to promote wound healing and soft tissue defects when used alone [29][30][31] or in combination with platelet rich plasma (PRP) and fat graft [32][33][34].…”

Application of 3D Bioprinting Technologies to the Management and Treatment of Diabetic Foot Ulcers

“…Autologous BM-MSCs administered to wounds accelerated wound closure and revascularization in the dermis and increased the thickness of the wound bed [ 40 , 96 , 97 , 98 , 99 , 100 , 101 ]. The therapeutic effects of BM-MSCs include modulation of the inflammatory responses, stimulation of angiogenesis and promotion of proliferation of keratinocytes and fibroblasts by the release of growth factors [ 102 , 103 , 104 ]. Other MSCs, such as those derived from adipose tissues and peripheral blood, also produced similar therapeutic effects in pre-clinical studies, highlighting their potential in treating chronic wounds in diabetic patients ( Table 1 ).…”

Clinical Translational Potential in Skin Wound Regeneration for Adipose-Derived, Blood-Derived, and Cellulose Materials: Cells, Exosomes, and Hydrogels

“…There have been considerable advancements in the understanding of the biochemical pathways and mechanisms underlying skin regenerative therapies, leading to explorations into the use of cells and cell-derived cytokines and exosomes, as well as hydrogels (recently reviewed in [ 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 ]) ( Table 1 ). While decellularized dermal scaffolds are routinely employed [ 20 ], only a PDGF (Platelet Derived Growth Factor)-related product has received regulatory approval among the cytokines, while no cell therapy has widespread approval in the U.S. [ 21 , 22 ].…”