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.

Introduction: The biological role of mesenchymal stem cells (MSCs) in wound healing has been demonstrated. However, there were limited studies on the healing effect of secretome which consists of many biological factors secreted by MSCs. In this study, we aimed to compare the therapeutic effects of secretome with MSCs on facilitating wound healing. Methods: Green fluorescent protein labelled adipose-derived MSCs (GFP-ADMSCs) or secretome was injected in the full-thickness skin excision model on SD rats. The wound healing process was evaluated by calculating the healing rate and the histological examinations on skin biopsy. The cell viability, proliferation and mobility of the rat dermal fibroblasts were compared after different treatments. The inflammatory response in macrophages was indicated by the level of nitric oxide (NO) and inflammatory cytokines through NO assay and ELISA. Results: On day 5 and day 14, both MSCs and secretome accelerated the wound healing, secretome further enhanced the process. GFP-MSCs were detected 10 days after transplantation. The level of IL-6 and TNF-α in blood was reduced after MSCs and secretome treatments. The expressions of VEGF and PCNA were increased after treatment, higher intensity of VEGF was observed in secretome-injected tissue. The concentrations of total protein and VEGF in secretome were 2.2 ± 0.5 mg/mL and 882.0 ± 72.7 pg/mL, respectively. The cell viability and proliferation of FR were promoted significantly after the treatment. The scratch test showed that secretome accelerated the wound healing speed. Secretome reduced the metabolism of macrophages remarkably, but it did not decrease the level of macrophage-secreted NO. The expression of the pro-inflammatory cytokines (IL-6, MCP-1 and TNF-α) was downregulated significantly. Conclusion: Our study indicated both MSCs and MSCs-derived secretome enhanced the wound healing process in early phase. Secretome further promoted the healing effects through promoting the fibroblast proliferation and migration and suppressing the inflammatory response.

Burns are common injuries, but their treatment remains challenging due to the complex nature of the wound healing process. Burn wounds are classified into different categories based on their size and depth. Treatment modalities vary significantly across these categories, primarily focusing on the inflammation, proliferation, and remodeling phases of burn wound healing. This review summarizes current research on various approaches to enhance burn wound recovery, including advancements in wound dressings, the use of platelet-rich plasma, stem cells, their soluble factors primarily in the form of secretomes or extracellular vesicles, and nano-technologies. Additionally, advancements in modernized traditional medicine are discussed to give a new aspect for burn wound healing. This review also summarizes the barriers in translating bench research to clinical practice in burn wound treatment methods. For an effective translation, researchers and industrial partners should work more closely, while regulatory bodies should streamline the approval procedure.

Atopic dermatitis (AD) is a chronic inflammatory skin condition characterized by itching, redness, and dryness, significantly impacting the quality of life of affected individuals. With a rising prevalence across diverse demographics, understanding AD is crucial due to its systemic nature and association with comorbidities such as asthma and allergic rhinitis, as well as its psychosocial implications. The pathophysiology of AD involves a complex interplay of genetic predispositions and environmental triggers, leading to dysbiosis and increased susceptibility to superinfection. Clinically, AD manifests variably across age groups, with distinct presentations in pediatric and adult populations. Diagnosis is primarily based on clinical assessment criteria, supplemented by differential diagnoses and, when necessary, skin tests for allergies. Current management strategies encompass topical therapies, including moisturizers, corticosteroids, and calcineurin inhibitors, alongside systemic treatments such as antihistamines, immunosuppressants, and biologics. Lifestyle modifications, including trigger avoidance and effective skin care routines, are essential components of comprehensive care. Emerging novel therapies targeting specific biomarkers are currently under investigation in clinical trials, offering promising avenues for more effective management. However, challenges remain in optimizing treatment protocols and addressing the multifaceted nature of AD. In conclusion, this review highlights the need for continued research and awareness regarding atopic dermatitis. A multidisciplinary approach to management is essential to enhance patient outcomes and address the complexities of this prevalent and impactful condition.

Our previous study reported that mesenchymal stem cells (MSCs) accelerated the wound healing process through anti-inflammatory, anti-apoptotic, and pro-angiogenetic effects in a rodent skin excision model. NF3 is a twin-herb formula, which presents similar effects in promoting wound healing. Research focusing on the interaction of MSCs and Chinese medicine is limited. In this study, we applied MSCs and the twin-herb formula to the wound healing model and investigated their interactions. Wound healing was improved in all treatment groups (MSCs only, NF3 only, and MSCs + NF3). The combined therapy further enhanced the effect: more GFP-labelled ADMSCs, collagen I and collagen III expression, Sox9 positive cells, and CD31 positive cells, along with less ED-1 positive cells, were detected; the expressions of proinflammatory cytokine IL-6 and TNF-α were downregulated; and the expression of anti-inflammatory cytokine IL-10 was upregulated. In vitro, NF3 promoted the cell viability and proliferation ability of MSCs, and a higher concentration of protein was detected in the NF3-treated supernatant. A proteomic analysis showed there were 15 and 22 proteins in the supernatants of normal ADMSCs and NF3-treated ADMSCs, respectively. After PCR validation, the expressions of 11 related genes were upregulated. The results of a western blot suggested that the TGFβ/Smad and Wnt pathways were related to the therapeutic effects of the combined treatment. Our study suggests for the first time that NF3 enhanced the therapeutic effect of MSCs in the wound healing model and the TGFβ/Smad and Wnt pathways were related to the procedure.