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<p>Cutaneous wound healing is a tightly regulated biological process that restores tissue integrity following injury. Dysregulation of inflammation, fibroblast activity, extracellular matrix remodeling, and angiogenesis can result in delayed healing or pathological scarring, including hypertrophic scars and keloids. Conventional scar-management strategies, such as intralesional corticosteroids, surgical excision, radiotherapy, laser therapy, cryotherapy, silicone-based products, and pressure therapy, remain limited by variable efficacy, recurrence, adverse effects, and inconsistent long-term outcomes. Consequently, regenerative approaches based on adipose-derived mesenchymal stromal cells (ASCs) and ASC-derived acellular products have attracted increasing attention This narrative review synthesizes current evidence regarding ASC-based therapies and ASC-derived acellular products, including conditioned medium, soluble factors, ASC-derived nanovesicle therapy (extracellular vesicle preparations), and apoptotic extracellular vesicles, in cutaneous wound healing and pathological scar modulation. Particular emphasis is placed on scar-relevant mechanisms, including regulation of inflammation and macrophage polarization, modulation of fibroblast and myofibroblast activity, collagen remodeling, angiogenesis, re-epithelialization, transforming growth factor-β/Smad signaling, α-smooth muscle actin expression, and matrix metalloproteinase/tissue inhibitor of metalloproteinase balance. The review also positions ASC-derived products in relation to extracellular vesicles obtained from other sources, including placental, milk-derived, and plant-derived vesicles, and discusses emerging engineering strategies involving genetically modified ASCs, engineered extracellular vesicles, biomaterial-assisted delivery systems, and controlled-release platforms. Current evidence, which remains predominantly preclinical and methodologically heterogeneous, suggests that ASC-based therapies and ASC-derived acellular products may support tissue repair and attenuate pathways associated with pathological scar formation. However, substantial translational barriers remain, including donor-related variability, product heterogeneity, incomplete standardization of isolation and characterization methods, uncertain dose definitions, storage limitations, long-term safety concerns, and regulatory challenges. Well-designed clinical studies and standardized manufacturing frameworks are required before these approaches can be routinely integrated into wound-care and scar-management practice.</p>

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Adipose-derived mesenchymal stromal cells and their acellular derivatives in cutaneous wound healing and pathological scarring: a narrative review

  • 期刊论文

  • 发表日期：

    2026年7月11日

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  • Nazanin Akbari,
  • Banafsheh Heidari,
  • Mehrangiz totonchi

摘要

Cutaneous wound healing is a tightly regulated biological process that restores tissue integrity following injury. Dysregulation of inflammation, fibroblast activity, extracellular matrix remodeling, and angiogenesis can result in delayed healing or pathological scarring, including hypertrophic scars and keloids. Conventional scar-management strategies, such as intralesional corticosteroids, surgical excision, radiotherapy, laser therapy, cryotherapy, silicone-based products, and pressure therapy, remain limited by variable efficacy, recurrence, adverse effects, and inconsistent long-term outcomes. Consequently, regenerative approaches based on adipose-derived mesenchymal stromal cells (ASCs) and ASC-derived acellular products have attracted increasing attention This narrative review synthesizes current evidence regarding ASC-based therapies and ASC-derived acellular products, including conditioned medium, soluble factors, ASC-derived nanovesicle therapy (extracellular vesicle preparations), and apoptotic extracellular vesicles, in cutaneous wound healing and pathological scar modulation. Particular emphasis is placed on scar-relevant mechanisms, including regulation of inflammation and macrophage polarization, modulation of fibroblast and myofibroblast activity, collagen remodeling, angiogenesis, re-epithelialization, transforming growth factor-β/Smad signaling, α-smooth muscle actin expression, and matrix metalloproteinase/tissue inhibitor of metalloproteinase balance. The review also positions ASC-derived products in relation to extracellular vesicles obtained from other sources, including placental, milk-derived, and plant-derived vesicles, and discusses emerging engineering strategies involving genetically modified ASCs, engineered extracellular vesicles, biomaterial-assisted delivery systems, and controlled-release platforms. Current evidence, which remains predominantly preclinical and methodologically heterogeneous, suggests that ASC-based therapies and ASC-derived acellular products may support tissue repair and attenuate pathways associated with pathological scar formation. However, substantial translational barriers remain, including donor-related variability, product heterogeneity, incomplete standardization of isolation and characterization methods, uncertain dose definitions, storage limitations, long-term safety concerns, and regulatory challenges. Well-designed clinical studies and standardized manufacturing frameworks are required before these approaches can be routinely integrated into wound-care and scar-management practice.