The Potential of MSC-Based Cell-Free Therapy in Wound Healing—A Thorough Literature Review

Abstract

A wound is an interruption of the normal anatomic structure and function of the skin, which is critical in protecting against foreign pathogens, regulating body temperature and water balance. Wound healing is a complex process involving various phases, including coagulation, inflammation, angiogenesis, re-epithelialization, and re-modeling. Factors such as infection, ischemia, and chronic diseases such as diabetes can compromise wound healing, leading to chronic and refractory ulcers. Mesenchymal stem cells (MSCs) have been used to treat various wound models due to their paracrine activity (secretome) and extracellular vehicles (exosomes) that contain several molecules, including long non-coding RNAs (lncRNAs), micro-RNAs (miRNAs), proteins, and lipids. Studies have shown that MSCs-based cell-free therapy using secretome and exosomes has great potential in regenerative medicine compared to MSCs, as there are fewer safety concerns. This review provides an overview of the pathophysiology of cutaneous wounds and the potential of MSCs-based cell-free therapy in each phase of wound healing. It also discusses clinical studies of MSCs-based cell-free therapies.

Exosome-Mediated Antigen Delivery: Unveiling Novel Strategies in Viral Infection Control and Vaccine Design

“…Moreover, the use of MSCs has shown iatrogenic effects [ 204 ]. The injection of MSCs might alter their viability and result in the inoculation of necrotic byproducts, thereby exacerbating tissue inflammation [ 205 ]. Upon intravenous injection, transplanted MSCs are prone to senescence and, in some cases, have been reported as tumorigenic [ 206 ].…”

“…Finally, MSC-derived exosomes could be used as favorable substitutes for synthetic skin grafts in wound healing. By mitigating inflammatory pathways and up-regulating pro-angiogenic pathways, they could contribute to proper tissue reparation [ 205 ]. miRNAs may also diminish the excessive differentiation of myofibroblasts by inhibiting the TGF-β signaling pathway, thus tempering collagen deposition and tissue fibrosis [ 221 ].…”

Exosomal noncoding RNA: A potential therapy for retinal vascular diseases

“…An evaluation was conducted to assess whether exosomes derived from MSCs could alleviate dry eye symptoms. This study evaluated patients with dry eye conditions after refractive surgery and those associated with blepharospasm ( Table 1 ; the trial was registered at ClinicalTrials.gov: NCT05738629 ), 123 , 124 as well as dry eye syndrome resulting from chronic graft-versus-host disease (cGvHD) ( Table 1 ; the trial was registered at ClinicalTrials.gov: NCT04213248 ). 125 , 126 In addition, clinical trials are under way to evaluate the safety and efficacy of MSC exosomes in treating vision loss caused by retinitis pigmentosa ( Table 1 ; the trial was registered at ClinicalTrials.gov: NCT05413148 ) 127 and macular holes associated with vitrectomy and internal limiting membrane peeling ( Table 1 ; the trial was registered at ClinicalTrials.gov: NCT03437759 ).…”

Exosomal microRNA-Based therapies for skin diseases

“…Furthermore, MSC-Exos have similar functional elements to their parent MSCs, which can naturally target inflammatory sites and readily fuse with inflammatory cells [ 12 ], apoptotic cells, the vascular endothelium, and tissue-derived stem cells, to modulate their behavior [ 13 ]. Notably, owing to their nanosize and biological origin, MSC-Exos possess outstanding capabilities to penetrate the stratum corneum barrier and reach the deep epidermis, dermis, and subcutaneous tissue [ 14 ]. When studying the function of exosomes, the exosome inhibitor GW4869 is often used to inhibit the release of exosomes by MSCs and thereby reverse the therapeutic effect [ 15 ].…”