Adipose-Derived Stem Cell Products and Combination Therapies for the Treatment of Pathological Scars: A Review of Current Preclinical and Clinical Studies

Nayla Majeda Alfarafisa,1,2,* Yoan Chou,3,* Resti Santika,2,4 Betha Egih Riestiano,2,5 Hardisiswo Soedjana,5 Mas Rizky AA Syamsunarno1,2 1Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, West Java, Indonesia; 2Metabolic in Medicine Working Group Study, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Graduate School of Master Program in Anti Aging and Aesthetic Medicine, Faculty of Medicine, Universitas Padjadjaran, Jatinangor, West Java, Indonesia; 4Faculty of Medicine, Universitas Padjadjaran, Jatinangor, West Java, Indonesia; 5Division of Plastic Reconstructive and Aesthetic Surgery, Department of Surgery, Faculty of Medicine Universitas Padjadjaran - Dr. Hasan Sadikin General Hospital, Bandung, Indonesia*These authors contributed equally to this workCorrespondence: Nayla Majeda Alfarafisa, Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jalan Raya Bandung – Sumedang Km 21, Jatinangor, West Java, 45363, Indonesia, Tel +62-22-7795594, Email [email protected]: Pathological scars, including hypertrophic, keloid, and atrophic scars, remain challenging to treat, with current therapies offering limited success. Adipose-derived stem cell (ADSC) products, classified into cell-based therapies (stromal vascular fraction [SVF], ADSCs) and cell-free therapies (adipose tissue extract [ATE], secretomes, exosomes, extracellular vesicles), have emerged as potential treatments.Purpose: This review examines the therapeutic potential of ADSC products for pathological scars in preclinical and clinical trials, aiming to bridge the gap between experimental research and clinical application. The effectiveness of ADSC products as monotherapies and in combination with other treatments has also been explored.Methods: A comprehensive literature search followed the PICO framework, utilizing electronic databases such as PubMed and Scopus. Original research articles, including both preclinical and clinical trials, were included.Results: This review included 43 studies that demonstrated the potential of ADSC products to improve pathological scars. ADSC products improve scar texture by regulating ECM, promoting adipogenesis and angiogenesis, and reducing inflammation in hypertrophic and keloid scars. In addition, ADSC products also prevented collagen degradation in atrophic scars. Although their effectiveness varied, ADSC products also showed potential when combined with treatments such as fractional CO2 laser, PRP, botulinum toxin, and photo-modulation.Conclusion: ADSC products show promise in treating pathological scars, with varying effectiveness in monotherapy or combination therapy. Keywords: adipose-derived stem cells, atrophic scars, fibroblast, hypertrophic scars, keloid scars