Key Takeaways & Executive Findings
- ā¢ā¢ ASCs exhibit potent immunosuppressive effects through direct cellācell interactions with immune cells (T cells, macrophages, B cells) and indirect paracrine mechanisms involving cytokines, growth factors, and extracellular vesicles. ā¢ ASCs are closely related to skin tissue, making them ideal for regenerative therapy in immune-related skin diseases, with advantages over other mesenchymal stem cells in terms of harvest ease and immunomodulatory potency. ā¢ Preclinical and clinical studies demonstrate promising therapeutic outcomes of ASCs in treating autoimmune skin diseases, though challenges such as adverse reactions and standardization remain. ā¢ The paracrine mechanisms, particularly ASC-secreted extracellular vesicles, are central to the immunomodulatory effects and may offer cell-free therapeutic alternatives.
Abstract
Adipose-derived stem cells (ASCs) are a critical adult stem cell subpopulation and are widely utilized in the fields of regenerative medicine and stem cell research due to their abundance, ease of harvest, and low immunogenicity. ASCs, which are homologous with skin by nature, can treat immune-related skin diseases by promoting skin regeneration and conferring immunosuppressive effects, with the latter being the most important therapeutic mechanism. ASCs regulate the immune response by direct cellācell communication with immune cells, such as T cells, macrophages, and B cells. In addition to cellācell interactions, ASCs modulate the immune response indirectly by secreting cytokines, interleukins, growth factors, and extracellular vesicles. The immunomodulatory effects of ASCs have been exploited to treat many immune-related skin diseases with good therapeutic outcomes. This article reviews the mechanisms underlying the immunomodulatory effects of ASCs, as well as progress in research on immune-related skin diseases.
1. Introduction
Immune-related skin diseases are a type of damage caused by disorders of the immune system, which are characterized by overactivated immune cells, high levels of pro-inflammatory factors, and a series of complex immune responses. Clinical symptoms of immune-related skin disease include fibrosis, redness, swelling, itching, and dandruff of the skin [1]. Topical and oral immunosuppressive drugs are the most widely used to treat immune-associated skin diseases, and new, more targeted approaches to treatment are being developed, but existing methods are still limited by the long course of treatment, limited efficacy, and significant expense [2].
ASCs are a type of mesenchymal stem cells (MSCs) derived from adipose tissue, also originate from the mesoderm, and are closely related to the skin. ASCs can thus be used to replenish and treat damaged skin tissue. Compared to other MSCs, ASCs have a potent immunosuppressive effect, which is a significant treatment advantage for immune-related skin diseases [3]. ASCs undergo cellācell interactions with a variety of immune cells, including T cells, macrophages, B cells, dendritic cells (DCs), and natural killer cells (NK cells). Paracrine mechanisms of ASCs also indirectly regulate the immune system via secretion of cytokines, growth factors, anti-inflammatory mediators, active enzymes, and extracellular vesicles (EVs). ASC-secreted EVs and apoptotic ASCs have similar therapeutic benefits to viable ASCs, suggesting that the paracrine mechanisms of ASCs are central to their immunomodulatory effects [4]. The present review describes ASC immunomodulatory mechanisms that contribute to their therapeutic effects in treatment of immune-related skin diseases and summarizes the progress of preclinical research and clinical application of ASC treatment of autoimmune skin diseases. In addition, the challenges and adverse reactions faced by ASCs in clinical application are also mentioned.
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Tianyi Sun, Cheng Zhou, Feng Lu, Ziqing Dong, Jianhua Gao, Bin Li (2026). Adipose-derived stem cells in immune-related skin disease: a review of current research and underlying mechanisms. Stem Cell Research & Therapy. https://doi.org/10.1186/s13287-023-03561-8
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Frequently Asked Questions
What are adipose-derived stem cells (ASCs)?
ASCs are adult mesenchymal stem cells derived from adipose tissue. They are abundant, easy to harvest via liposuction, and have low immunogenicity, making them attractive for regenerative medicine and immunomodulatory therapies.
How do ASCs treat immune-related skin diseases?
ASCs treat immune-related skin diseases by promoting skin regeneration and exerting immunosuppressive effects. They modulate immune responses through direct cellācell interactions with immune cells and indirectly via secretion of cytokines, growth factors, and extracellular vesicles.
What are the advantages of ASCs over other mesenchymal stem cells?
Compared to bone marrow or umbilical cord MSCs, ASCs can be harvested in larger quantities with less discomfort, and they exhibit potent immunosuppressive effects, making them particularly suitable for treating immune-related skin conditions.
What is the role of extracellular vesicles in ASC therapy?
Extracellular vesicles secreted by ASCs carry bioactive molecules that mediate paracrine effects, contributing to immunomodulation and tissue repair. They may offer a cell-free therapeutic alternative with similar benefits to viable ASCs.
What are the challenges in clinical application of ASCs?
Challenges include standardization of isolation and expansion protocols, potential adverse reactions, long-term safety concerns, and regulatory hurdles. Further research is needed to optimize clinical translation.
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