Concise Review: Clinical Translation of Wound Healing Therapies Based on Mesenchymal Stem Cells

AbstractObjectivesWound healing is a complex process with a sequence of restoring and inhibition events such as cell proliferation, differentiation, migration as well as adhesion. Mesenchymal stem cells (MSC) derived conditioned medium (CM) has potent therapeutic functions and promotes cell proliferation, anti-oxidant, immunosuppressive, and anti-apoptotic effects. The main aim of this research is to study the role of human umbilical cord-mesenchymal stem cells (UC-MSCs) derived CM in stimulating the proliferation of human keratinocytes (HaCaT).MethodsFirstly, MSC were isolated from human umbilical cords (UC) and the cells were then cultured in proliferative medium. We prepared and collected the CM after 72 h. Morphological changes were observed after the treatment of HaCaT cells with CM. To validate the findings, proliferation rate, clonal efficiency and also gene expression studies were performed.ResultsIncreased proliferation rate was observed and confirmed with the expression of Proliferating Cell Nuclear Antigen (PCNA) after treatment with HaCaT cells. Cell-cell strap formation was also observed when HaCaT cells were treated with CM for a period of 5–6 days which was confirmed by the increased expression of Collagen Type 1 Alpha 1 chain (Col1A1).ConclusionsOur results from present study depicts that the secretory components in the CM might play a significant role by interacting with keratinocytes to promote proliferation and migration. Thus, the CM stimulates cellular proliferation, epithelialization and migration of skin cells which might be the future promising application in wound healing.

Download Full-text

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

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02288-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jianxin Yan ◽

Jiaji Liang ◽

Yingxuan Cao ◽

Mariya M. El Akkawi ◽

Xuan Liao ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Chronic Wounds ◽

Blood Perfusion ◽

Systemic Administration ◽

Critical Parameters ◽

Administration Routes ◽

Positive Effects ◽

Systemic Treatments

Abstract Background Mesenchymal stem cells (MSCs) exert positive effects in chronic wounds. However, critical parameters, such as the most effective administration routes, remain unclear. Accordingly, the purpose of this study was to compare the effects of topical and systemic transplantation MSCs on diabetic ischemic wound healing and explored the underlying mechanisms. Method A diabetic ischemic wound model was created on the dorsal foot of type 2 diabetes mellitus (T2DM) rat. Bone marrow-derived mesenchymal stem cells (BM-MSCs) were administered via two routes: topical injection and intravenous (IV) infusion. Wound healing outcomes and blood glucose level were assessed dynamically. Meanwhile, blood flow recovery was evaluated in ischemic gastrocnemius muscles. The homing and transdifferentiation of mKate2-labeled BM-MSCs were assessed by fluorescence imaging and immunohistochemistry (IHC) analysis. Result Both topical and systemic treatments had a positive effect on the diabetic ischemic wound showing a significant reduction in wound area at day 14. Histological results showed an increase in the length of epithelial edges, collagen content, microvessel density in the wound bed, and a higher expression of vascular endothelial growth factor (VEGF). Meanwhile, systemic administration can ameliorate hyperglycemia and improve the blood perfusion of the ischemic hindlimb. BM-MSCs administered systemically were found distributed in wounded tissue and transdifferentiated into endothelial cells. Furthermore, BM-MSCs stimulated angiogenesis at wound sites by downregulating phosphatase and tensin homolog (PTEN) and activation of AKT signaling pathway. Conclusions The results demonstrated that both transplantation delivery method (topical and systemic) of BM-MSCs accelerated wound healing remarkably under pathological conditions. Nevertheless, systemic administration has the potential to ameliorate hyperglycemia and repair the damaged tissue.

Download Full-text

Chronic senescent human mesenchymal stem cells as possible contributor to the wound healing disorder after exposure to the alkylating agent sulfur mustard

Archives of Toxicology ◽

10.1007/s00204-020-02946-5 ◽

2021 ◽

Vol 95 (2) ◽

pp. 727-747

Author(s):

Simone Rothmiller ◽

Niklas Jäger ◽

Nicole Meier ◽

Thimo Meyer ◽

Adrian Neu ◽

...

Keyword(s):

Stem Cells ◽

Wound Healing ◽

Mesenchymal Stem Cells ◽

Alkylating Agent ◽

Chronic Wounds ◽

Sulfur Mustard ◽

Morphological Changes ◽

Human Mesenchymal Stem Cells ◽

Age Related

AbstractWound healing is a complex process, and disturbance of even a single mechanism can result in chronic ulcers developing after exposure to the alkylating agent sulfur mustard (SM). A possible contributor may be SM-induced chronic senescent mesenchymal stem cells (MSCs), unable to fulfil their regenerative role, by persisting over long time periods and creating a proinflammatory microenvironment. Here we show that senescence induction in human bone marrow derived MSCs was time- and concentration-dependent, and chronic senescence could be verified 3 weeks after exposure to between 10 and 40 µM SM. Morphological changes, reduced clonogenic and migration potential, longer scratch closure times, differences in senescence, motility and DNA damage response associated genes as well as increased levels of proinflammatory cytokines were revealed. Selective removal of these cells by senolytic drugs, in which ABT-263 showed initial potential in vitro, opens the possibility for an innovative treatment strategy for chronic wounds, but also tumors and age-related diseases.

Download Full-text