Chronic wounds are wounds that do not move through the normal stages of healing as expected. Instead of closing properly, they may remain open for months, creating ongoing pain, infection risk, limited mobility, and reduced quality of life. Common examples include diabetic foot ulcers, pressure ulcers, venous leg ulcers, and wounds that develop after radiation therapy.
These wounds are difficult to treat because they often involve more than just surface-level skin damage. According to the review, chronic wounds are influenced by inflammation, poor blood supply, infection, low oxygen levels, and impaired cell function within the wound environment. Because of these overlapping factors, standard wound care may help manage symptoms but may not fully correct the underlying problems that prevent healing.
In this review published in Frontiers in Cell and Developmental Biology, researchers examined how mesenchymal stem cells (MSCs) are being studied for chronic wound healing and skin regeneration. The review focused on how MSCs may support tissue repair, reduce inflammation, improve blood vessel formation, and help restore a healthier wound environment.
Why Chronic Wounds Are So Difficult to Heal
Normal wound healing involves a coordinated process of inflammation, tissue formation, blood vessel growth, and remodeling. In chronic wounds, this process becomes disrupted. The wound may remain stuck in a prolonged inflammatory state, preventing new tissue from forming properly.
The review explains that chronic wounds often involve several barriers to healing, including chronic inflammation, ineffective angiogenesis, and abnormal extracellular matrix remodeling. Angiogenesis is the formation of new blood vessels, which is especially important because healing tissue needs oxygen and nutrients to repair itself. When blood vessel growth is impaired, the wound environment becomes less supportive of recovery.
This is one reason researchers are interested in regenerative medicine approaches. Instead of only covering or cleaning the wound, MSC-based therapies are being studied for their ability to influence the biological environment that controls healing.
How Mesenchymal Stem Cells May Support Wound Repair
Mesenchymal stem cells are multipotent cells that can be found in several tissue sources, including umbilical cord, placenta, bone marrow, and other tissues. They are widely studied in regenerative medicine because of three major properties: immune modulation, paracrine signaling, and tissue repair support.
One of the most important ways MSCs may support wound healing is through paracrine signaling. This means MSCs release helpful bioactive factors that communicate with nearby cells. These signals may help reduce inflammation, encourage cell survival, promote new blood vessel growth, and support the formation of healthy new tissue.
The review describes several mechanisms involved in MSC-based wound repair, including:
- Reducing excessive inflammation
- Encouraging angiogenesis
- Supporting re-epithelialization
- Improving extracellular matrix remodeling
- Releasing growth factors and extracellular vesicles
- Helping restore balance in the wound microenvironment
Together, these actions may help shift chronic wounds away from a stalled inflammatory state and toward a more active healing process.
The Role of Umbilical Cord-Derived MSCs
The review also discussed umbilical cord-derived MSCs, which are especially relevant in regenerative medicine because of their favorable immunomodulatory properties and low immunogenicity. These qualities make them appealing for allogeneic use, meaning they may be used from a donor source rather than requiring cells from the same patient.
Clinical research involving umbilical cord-derived MSCs has shown encouraging findings in chronic wound settings. For example, the review summarized a pilot trial involving umbilical cord MSCs delivered both around the wound and intravenously in patients with diabetic foot ulcers. In that study, many patients experienced complete wound closure within a relatively short timeframe, with long-term outcomes and minimal adverse events reported.
The review also highlighted clinical trial data involving umbilical cord-derived MSCs for chronic diabetic ulcers and venous leg ulcers, with reported findings that included wound reduction, increased granulation tissue, healing improvements, and no serious adverse events in the listed trials.
Exosomes and Cell-Free Regenerative Approaches
Another important area discussed in the review is the use of MSC-derived extracellular vesicles and exosomes. These small particles are released by cells and carry signaling molecules that can influence healing activity. Researchers are increasingly interested in exosome-based approaches because they may provide many of the benefits associated with MSC signaling without requiring the direct use of whole cells.
The review described a randomized double-blind trial using Wharton’s jelly-derived MSC exosomes for diabetic foot ulcers. In that study, topical application of these exosomes was associated with significantly faster healing, with complete epithelialization occurring in a shorter average time compared with the control group.
This growing interest in exosomes reflects a broader trend in regenerative medicine: researchers are not only studying the cells themselves, but also the biological signals those cells release. These signals may play a major role in reducing inflammation, promoting tissue repair, and improving the wound-healing environment.
Innovations Improving MSC-Based Wound Therapy
The review also explained that the field is moving toward more advanced and targeted approaches. Researchers are studying ways to improve MSC survival, delivery, and consistency in the wound environment.
Some of the innovations discussed include biomaterial scaffolds, hydrogels, genetic engineering, extracellular vesicle-based therapies, and preconditioning strategies that may enhance the regenerative properties of MSCs before they are used. These methods are being explored to help MSCs remain active longer, deliver stronger repair signals, and better adapt to the difficult conditions found in chronic wounds.
The goal is not simply to apply MSCs to a wound, but to create a more effective regenerative system that supports healing from multiple angles.
Why This Research Matters
Chronic wounds can be physically, emotionally, and financially burdensome. They can limit daily activity, increase the risk of infection, and become especially serious for patients with diabetes, poor circulation, or long-term inflammatory conditions. Because chronic wounds often involve multiple biological problems at once, therapies that can address inflammation, blood vessel growth, and tissue repair together are especially valuable.
This review highlights the growing potential of MSC-based therapies as a regenerative approach for chronic wound healing. The authors emphasize that MSCs may be best understood as supportive biological tools that work alongside standard wound care rather than simply replacing it.
As the field continues to develop, future research will help clarify which MSC sources, delivery methods, and treatment strategies are most effective for different types of chronic wounds. Continued work in standardization and long-term clinical trials may also help bring these therapies closer to routine clinical use.
A Promising Path Forward for Skin Regeneration
Mesenchymal stem cells continue to represent an exciting area of research in wound healing and skin regeneration. Their ability to regulate inflammation, support angiogenesis, release healing signals, and improve the wound microenvironment makes them a strong focus within regenerative medicine.
While more clinical research is still needed, this review shows meaningful progress in the study of MSC-based therapies for chronic wounds. From umbilical cord-derived MSCs to MSC-derived exosomes and advanced biomaterial delivery systems, regenerative medicine is opening new possibilities for supporting tissue repair and improving outcomes for patients with difficult-to-heal wounds.
Source Tang Y, Su T, Huang B, Xu Q, Chen Q, Zhang S, Li W. Advancements in mesenchymal stem cell therapy for chronic wounds: challenges, innovations, and future directions. Front Cell Dev Biol. 2026;13:1730032. doi: 10.3389/fcell.2025.1730032. Available from: https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2025.1730032/full
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