Mesenchymal stem cell–based therapy for nonhealing wounds: today and tomorrow

Abstract

Although advancements have been made with traditional therapies, the treatment of chronic nonhealing wounds still remains a tough challenge. In the past two decades, mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for nonhealing wounds because of their characteristics including self-renewal and a multidirectional differentiation ability and their easy collection and weak immunogenicity. There is a growing body of basic scientific studies that shed light on the functional mechanism of MSCs in modulating nonhealing wounds. Furthermore, critical advances have been achieved using MSC-based therapy in preclinical animal models as well as in clinics trials. In this present review, we summarize the mechanisms of MSCs and highlight the important preclinical and clinical trials of MSC therapy for nonhealing wounds. In particular, the combination of MSCs transplantation and tissue-engineered skin is addressed as a new strategy to optimize the delivery efficiency and therapeutic potential. Additionally, the current drawbacks of MSC therapy and the potential to further optimize the use of MSCs are implied.

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

“…Indeed, numerous studies about this approach have produced encouraging results. They included both preclinic trials with animal models, such as mouse, rat, dog, or pig, as well as clinic ones with humans (Nuschke, 2014;Li et al, 2015b;Maranda et al, 2016). Both autologous and allogenous MSC from different origins have been used, including bone marrow, adipose tissue, umbilical cord, and the stromal vascular fraction, among others (Teng et al, 2014).…”

Nanotechnology-Driven Therapeutic Interventions in Wound Healing: Potential Uses and Applications

“…130 Current applications of SCs include local delivery to wounds using dressings, sprays, injections, and systemic administration. Nanotechnology-based approaches were explored to generate a nanomatrix with tailored biophysical properties to better control the differentiation of stem cells.…”

Local management of deep cavity wounds – current and emerging therapies

“…In recent times, significant enhancements have been made in our understanding of stem cell biology as a clinical tool and treatment for difficult-toheal wounds. Mesenchymal stem cell (MSC) therapy has emerged as a promising potential treatment for nonhealing wounds, 51 with the US National Institutes of Health (NIH) currently registering 521 studies being undertaken into MSCs. 52 MSCs are multipotent adult stem cells, which possess the ability to differentiate into several mesenchymal lineages including tendon, bone, cartilage, and adipose tissue.…”

“…53 Due to the fact that they do not express class II major histocompatibility complexes (MHCs) on their cell surfaces, they are immune-privileged cells, making them suitable for allogenic transplantation. 53 There is growing evidence that endogenous stem cells play a cell role in normal tissue repair of almost all tissue types, 51 but this endogenous function can sometimes be overwhelmed by severe injury, old age, hostile microenvironment, and immunosuppression. 54 There is a growing body of work investigating the ability of MSCs to secrete a multitude of bioactive molecules, including SDF-1, VEGF, and TGF-beta, and the effect of these molecules on endogenous stem cell recruitment.…”

“…First, because of the small percentage of bone marrowderived stem cells that can be isolated and the large volumes of tissue required to do so. 56 Second, there is a possibility that these cells may undergo unfavorable changes 51,53,56 and have a potential carcinogenic effect. 53,56 Finally, there remain significant ethical problems behind the use of such cells.…”