Research progress on the application of adipose-derived stem cells and their derivatives in different wound healing

doi:10.3877/cma.j.issn.1673-9450.2025.05.013

Abstract

Abstract:

Wound healing is regulated by the interactions of various cells and a complex network of signaling pathways. When the local microenvironment is dysregulated，wound healing can be delayed or even fail to occur，and refractory wounds remain a major clinical challenge. Adipose-derived stem cells （ADSCs），which are abundant and easily accessible，possess strong paracrine functions and multi-directional differentiation potential，playing a crucial role in wound repair and regeneration. This article reviews the biological characteristics of adipose-derived stem cells，the types and features of their derivatives，and their applications in different types of wound healing，aiming to provide new insights for future research on stem cell therapy in wound healing.

Key words: Wound healing, Adipose-derived stem cells, Derivatives, Chronic refractory wounds

Yuzhe Huang, Binsha Wu. Research progress on the application of adipose-derived stem cells and their derivatives in different wound healing[J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(05): 442-446.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhssyxfzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.1673-9450.2025.05.013

https://zhssyxfzz.cma-cmc.com.cn/EN/Y2025/V20/I05/442

References 64

［1］	Zhou C，Zhang B，Yang Y，et al. Stem cell-derived exosomes： emerging therapeutic opportunities for wound healing［J］. Stem Cell Res Ther，2023，14（1）：107.
［2］	Mascharak S，Talbott HE，Januszyk M，et al. Multi-omic analysis reveals divergent molecular events in scarring and regenerative wound healing［J］. Cell Stem Cell，2022，29（2）：315-327. e6.
［3］	Xiong S，Zhang J，Zhao Z，et al. NORAD accelerates skin wound healing through extracellular vesicle transfer from hypoxic adipose derived stem cells： miR-524-5p pathway and Pumilio protein mechanism［J］. Int J Biol Macromol，2024，279（Pt 4）：135621.
［4］	Wu B，Liu C，Wang T，et al. Comparison of the difference in the stemness changes of adipose-derived stem cell and dedifferentiated fat cell after fat transplantation： in vivo and in vitro evidence［J］. Aesthetic Plast Surg，2025，49（14）：4067-4081.
［5］	Cossu G，Birchall M，Brown T，et al. Lancet commission： stem cells and regenerative medicine［J］. Lancet，2018，391（10123）：883-910.
［6］	Mohamed-Ahmed S，Fristad I，Lie SA，et al. Adipose-derived and bone marrow mesenchymal stem cells： a donor-matched comparison［J］. Stem Cell Res Ther，2018，9（1）：168.
［7］	Zhang L，Yu Z，Liu S，et al. Advanced progress of adipose-derived stem cells-related biomaterials in maxillofacial regeneration［J］. Stem Cell Res Ther，2025，16（1）：110.
［8］	Al-Ghadban S，Bunnell BA. Adipose tissue-derived stem cells： immunomodulatory effects and therapeutic potential［J］. Physiology （Bethesda），2020，35（2）：125-133.
［9］	Han J，Li X，Liang B，et al. Transcriptome profiling of differentiating adipose-derived stem cells across species reveals new genes regulating adipogenesis［J］. Biochim Biophys Acta Mol Cell Biol Lipids，2023，1868（10）：159378.
［10］	Huayllani MT，Sarabia-Estrada R，Restrepo DJ，et al. Adipose-derived stem cells in wound healing of full-thickness skin defects： a review of the literature［J］. J Plast Surg Hand Surg，2020，54（5）：263-279.
［11］	Mazini L，Rochette L，Admou B，et al. Hopes and limits of adipose-derived stem cells （ADSCs） and mesenchymal stem cells （MSCs） in wound healing［J］. Int J Mol Sci，2020，21（4）：1306.
［12］	Czerwiec K，Zawrzykraj M，Deptuła M，et al. Adipose-derived mesenchymal stromal cells in basic research and clinical applications［J］. Int J Mol Sci，2023，24（4）：3888.
［13］	Stojanović S，Najman S. The effect of conditioned media of stem cells derived from lipoma and adipose tissue on macrophages' response and wound healing in indirect co-culture system in vitro［J］. Int J Mol Sci，2019，20（7）：1671.
［14］	Horie T，Hirata H，Sakamoto T，et al. Multiomics analyses reveal adipose-derived stem cells inhibit the inflammatory response of M1-like macrophages through secreting lactate［J］. Stem Cell Res Ther，2024，15（1）：485.
［15］	Zuccarini M，Giuliani P，Di Liberto V，et al. Adipose stromal/stem cell-derived extracellular vesicles： potential next-generation anti-obesity agents［J］. Int J Mol Sci，2022，23（3）：1543.
［16］	Yang S，Sun Y，Yan C. Recent advances in the use of extracellular vesicles from adipose-derived stem cells for regenerative medical therapeutics［J］. J Nanobiotechnology，2024，22（1）：316.
［17］	Zhang B，Wu Y，Mori M，et al. Adipose-derived stem cell conditioned medium and wound healing： a systematic review［J］. Tissue Eng Part B Rev，2022，28（4）：830-847.
［18］	Cai Y，Li J，Jia C，et al. Therapeutic applications of adipose cell-free derivatives： a review［J］. Stem Cell Res Ther，2020，11（1）：312.
［19］	Phillips MI，Tang YL. Genetic modification of stem cells for transplantation［J］. Adv Drug Deliv Rev，2008，60（2）：160-172.
［20］	Chen JG，Zhang EC，Wan YY，et al. Engineered hsa‐miR‐455‐3p‐abundant extracellular vesicles derived from 3D‐cultured adipose mesenchymal stem cells for tissue‐engineering hyaline cartilage regeneration［J］. Adv Healthc Mater，2024，13（18）：e2304194.
［21］	Perez-Estenaga I，Prosper F，Pelacho B. Allogeneic mesenchymal stem cells and biomaterials： the perfect match for cardiac repair?［J］. Int J Mol Sci，2018，19（10）：3236.
［22］	Song Y，You Y，Xu X，et al. Adipose‐derived mesenchymal stem cell‐derived exosomes biopotentiated extracellular matrix hydrogels accelerate diabetic wound healing and skin regeneration［J］. Adv Sci （Weinh），2023，10（30）：e2304023.
［23］	Dai R，Wang Z，Samanipour R，et al. Adipose‐derived stem cells for tissue engineering and regenerative medicine applications［J］. Stem Cells Int，2016，2016：6737345.
［24］	Gentile P，Garcovich S. Systematic review： adipose-derived mesenchymal stem cells，platelet-rich plasma and biomaterials as new regenerative strategies in chronic skin wounds and soft tissue defects［J］. Int J Mol Sci，2021，22（4）：1538.
［25］	Fakiha K. Adipose stromal vascular fraction： a promising treatment for severe burn injury［J］. Hum Cell，2022，35（5）：1323-1337.
［26］	Yuan Y，Shen S，Fan D. A physicochemical double cross-linked multifunctional hydrogel for dynamic burn wound healing： shape adaptability，injectable self-healing property and enhanced adhesion［J］. Biomaterials，2021，276：120838.
［27］	Jeschke MG，Rehou S，McCann MR，et al. Allogeneic mesenchymal stem cells for treatment of severe burn injury［J］. Stem Cell Res Ther，2019，10（1）：337.
［28］	Amini-Nik S，Dolp R，Eylert G，et al. Stem cells derived from burned skin-the future of burn care［J］. EBioMedicine，2018，37：509-520.
［29］	Huang L，Burd A. An update review of stem cell applications in burns and wound care［J］. Indian J Plast Surg，2012，45（2）：229-236.
［30］	Franck CL，Senegaglia AC，Leite LMB，et al. Influence of adipose tissue-derived stem cells on the burn wound healing process［J］. Stem Cells Int，2019，2019：2340725.
［31］	Li S，Zhao C，Shang G，et al. α-ketoglutarate preconditioning extends the survival of engrafted adipose-derived mesenchymal stem cells to accelerate healing of burn wounds［J］. Exp Cell Res，2024，439（1）：114095.
［32］	Wu Y，Liang T，Hu Y，et al. 3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing［J］. Regen Biomater，2021，8（3）：rbab014.
［33］	Shahmohammadi A，Samadian H，Heidari Keshel S，et al. Burn wound healing using adipose-derived mesenchymal stem cells and manganese nanoparticles in polycaprolactone/gelatin electrospun nanofibers in rats［J］. Bioimpacts，2024，14（5）：30193.
［34］	Filip R，Linea M，Maj-Lis T，et al. Safety & efficacy of adipose-derived stem cells in acute burns： a randomized placebo-controlled phase-I trial（ASCAB）［J］. J Burn Care Res，2024，45（Supple 1）：74–75.
［35］	Yu FX，Lee PSY，Yang L，et al. The impact of sensory neuropathy and inflammation on epithelial wound healing in diabetic corneas［J］. Prog Retin Eye Res，2022，89：101039.
［36］	van Netten JJ，Bus SA，Apelqvist J，et al. Definitions and criteria for diabetes‐related foot disease （IWGDF 2023 update）［J］. Diabetes Metab Res Rev，2024，40（3）：e3654.
［37］	Armstrong DG，Boulton AJM，Bus SA. Diabetic foot ulcers and their recurrence［J］. N Engl J Med，2017，376（24）：2367-2375.
［38］	Shi Y，Wang S，Wang K，et al. Relieving macrophage dysfunction by inhibiting SREBP2 activity： a hypoxic mesenchymal stem cells‐derived exosomes loaded multifunctional hydrogel for accelerated diabetic wound healing［J］. Small，2024，20（25）：e2309276.
［39］	Xu J，Liu X，Zhao F，et al. HIF1α overexpression enhances diabetic wound closure in high glucose and low oxygen conditions by promoting adipose-derived stem cell paracrine function and survival［J］. Stem Cell Res Ther，2020，11（1）：148.
［40］	Ouyang L，Qiu D，Fu X，et al. Overexpressing HPGDS in adipose-derived mesenchymal stem cells reduces inflammatory state and improves wound healing in type 2 diabetic mice［J］. Stem Cell Res Ther，2022，13（1）：395.
［41］	Yin D，Shen G. Exosomes from adipose‐derived stem cells regulate macrophage polarization and accelerate diabetic wound healing via the circ‐Rps5/miR‐124‐3p axis［J］. Immun Inflamm Dis，2024，12（6）：e1274.
［42］	Xie Y，Ni X，Wan X，et al. KLF5 enhances CXCL12 transcription in adipose-derived stem cells to promote endothelial progenitor cells neovascularization and accelerate diabetic wound healing［J］. Cell Mol Biol Lett，2025，30（1）：24.
［43］	Li Y，Li D，You L，et al. dCas9-Based PDGFR–β activation ADSCs accelerate wound healing in diabetic mice through angiogenesis and ECM remodeling［J］. Int J Mol Sci，2023，24（6）：5949.
［44］	Cianfarani F，Toietta G，Di Rocco G，et al. Diabetes impairs adipose tissue–derived stem cell function and efficiency in promoting wound healing［J］. Wound Repair Regen，2013，21（4）：545-553.
［45］	Tseng SL，Kang L，Li ZJ，et al. Adipose-derived stem cells in diabetic foot care： bridging clinical trials and practical application［J］. World J Diabetes，2024，15（6）：1162-1177.
［46］	Mrozikiewicz-Rakowska B，Szabłowska-Gadomska I，Cysewski D，et al. Allogenic adipose-derived stem cells in diabetic foot ulcer treatment： clinical effectiveness，safety，survival in the wound site，and proteomic impact［J］. Int J Mol Sci，2023，24（2）：1472.
［47］	Uzun E，Güney A，Gönen ZB，et al. Intralesional allogeneic adipose-derived stem cells application in chronic diabetic foot ulcer： phase I/2 safety study［J］. Foot Ankle Surg，2021，27（6）：636-642.
［48］	Huang YZ，Gou M，Da LC，et al. Mesenchymal stem cells for chronic wound healing： current status of preclinical and clinical studies［J］. Tissue Eng Part B Rev，2020，26（6）：555-570.
［49］	Peng Q，Qian Y，Xiao X，et al. Advancing chronic wound healing through electrical stimulation and adipose‐derived stem cells［J］. Adv Healthc Mater，2025，14（10）：e2403777.
［50］	Visconti AJ，Sola OI，Raghavan PV. Pressure injuries prevention，evaluation，and management［J］. Am Fam Physician，2023，108（2）：166-174.
［51］	Zuniga J，Mungai M，Chism L，et al. Pressure ulcer prevention and treatment interventions in Sub-Saharan Africa： a systematic review［J］. Nurs Outlook，2024，72（3）：102151.
［52］	Mervis JS，Phillips TJ. Pressure ulcers： pathophysiology，epidemiology，risk factors，and presentation［J］. J Am Acad Dermatol，2019，81（4）：881-890.
［53］	Jin C，Zhao R，Hu W，et al. Topical hADSCs-HA gel promotes skin regeneration and angiogenesis in pressure ulcers by paracrine activating PPARβ/δ pathway［J］. Drug Des Devel Ther，2024，18：4799-4824.
［54］	Su Y，Huang Z，Chen Y，et al. Exosomes from miR-21-5p-modified adipose-derived stem cells promote wound healing by regulating M2 macrophage polarization in a rodent model of pressure ulcer［J］. J Mol Histol，2025，56（3）：135.
［55］	Schul MW，Melin MM，Keaton TJ. Venous leg ulcers and prevalence of surgically correctable reflux disease in a national registry［J］. J Vasc Surg Venous Lymphat Disord，2023，11（3）：511-516.
［56］	Probst S，Bobbink P，Séchaud L，et al. Venous leg ulcer recurrences – the relationship to self‐efficacy，social support and quality of life – a mixed method study［J］. J Adv Nurs，2021，77（1）：367-375.
［57］	John J，Tate S，Price A. Non-surgical treatment for arterial leg ulcers： a narrative review［J］. J Wound Care，2022，31（11）：969-978.
［58］	Elsharkawi M，Ghoneim B，Westby D，et al. Adipose-derived stem cells in patients with venous ulcers： systematic review［J］. Vascular，2023，31（5）：989-993.
［59］	Holm JS，Toyserkani NM，Sorensen JA. Adipose-derived stem cells for treatment of chronic ulcers： current status［J］. Stem Cell Res Ther，2018，9（1）：142.
［60］	Feng Z，Zhang Y，Yang C，et al. Bioinspired and inflammation‐modulatory glycopeptide hydrogels for radiation‐induced chronic skin injury repair［J］. Adv Healthc Mater，2023，12（1）：e2201671.
［61］	Shen J，Jiao W，Yang J，et al. In situ photocrosslinkable hydrogel treats radiation-induced skin injury by ROS elimination and inflammation regulation［J］. Biomaterials，2025，314：122891.
［62］	Lin Z，Shibuya Y，Imai Y，et al. Therapeutic potential of adipose-derived stem cell-conditioned medium and extracellular vesicles in an in vitro radiation-induced skin injury model［J］. Int J Mol Sci，2023，24（24）：17214.
［63］	Yao WD，Zhou JN，Tang C，et al. Hydrogel microneedle patches loaded with stem cell mitochondria-enriched microvesicles boost the chronic wound healing［J］. ACS Nano，2024，18（39）：26733-26750.
［64］	Zhu Y，Liu X，Chen X，et al. Adipose-derived stem cells apoptosis rejuvenate radiation-impaired skin in mice via remodeling and rearranging dermal collagens matrix［J］. Stem Cell Res Ther，2024，15（1）：324.

[1]	Ziyuan Zhang, Duyin Jiang. Exploring the mechanism of sea buckthorn in promoting burn wound repair based on network pharmacology and molecular docking [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(05): 404-411.
[2]	Xiangyang Zhao, Jing Zhao, Baoli Chen, Zhijuan Wang, Chi Xue, Fen Wang, Xiaochun Jiao, Lina Wang, Qin Zhou. Research progress on non-pharmacological analgesic management for procedural pain in chronic refractory wounds [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(05): 436-441.
[3]	Yixuan Gao, Xiaowei Zhang, Baolong Li, Wenzhi Hu, Yonghong Hao, Xiaofang Zou. Clinical efficacy analysis of full thickness microskin grafting in the treatment of autoimmune disease- related ulcers [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(04): 290-295.
[4]	Fang Jin, Songjia Tang, Chunmao Han, Xingang Wang, Wei Zhang. Application of adipose tissue and its derivatives in skin repair and regeneration [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(04): 352-357.
[5]	Jiangtao Liu, Jinshen Pan, Yiyong Wang, Yifeng Lin, Shurun Huang. Clinical efficacy of pedicle perforator flap in repairing deep tissue exposed wounds in the hands， feet，and ankles [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(03): 212-219.
[6]	Yantong Zhou, Cheng Wang. Research progress on the application of different new dressings in wounds [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(02): 163-168.
[7]	Shunxin Jin, Jiayuecheng Pang, Shichu Xiao. Advances in the mechanism and clinical application of rete ridges microstructure-based grafts in promoting wound healing [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2025, 20(02): 174-178.
[8]	Yu Li, Peng Wang, He Lu, Rongqin Feng, Juntao Han. Clinical observation of low-frequency pulse electrical stimulation in the treatment of deep partialthickness burn wounds [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(06): 474-478.
[9]	Changling Liu, Jinli Zhang, Zhi Zhang, Xiaojian Li, Wenbin Tang, Yiping Hu, Bin Chen, Xiaona Xie. Effects of gelatin methacryloyl hydrogel loaded with exosomes from human adipose-derived stem cells on the proliferation and migration of human skin fibroblasts [J]. Chinese Journal of Injury Repair and Wound Healing(Electronic Edition), 2024, 19(06): 517-525.
[10]	Ya Li, Subo Zhuang. Retrospective study on clinical distribution characteristics and drug resistance of pathogenic bacteria in 124 cases of chronic refractory wounds [J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2025, 19(04): 230-241.
[11]	Lina Wang, Yuan Lv, Liang Sun, Qiang Yuan, Yuhui Nie, Bo Liu. Clinical observation on the promotion of postoperative rehabilitation of hemorrhoids by egg yolk oil combined with the external washing prescription for wound healing in the department of anorectal surgery [J]. Chinese Journal of Operative Procedures of General Surgery(Electronic Edition), 2025, 19(04): 457-460.
[12]	Yizhen Hou, Kun Zhang, Xianming Lu, Xiaolei Zhang. Cystostomy leads to huge bladder stones: a case report [J]. Chinese Journal of Endourology(Electronic Edition), 2025, 19(02): 259-261.
[13]	Haoyue Zhang, Huiting Zhu, Honghao Wu, Yehuang Wang, Ling Ji, Yaxian Wang, Yang Zhang. A prospective， multicentre and randomised controlled study of initiative irrigation and drainage treatment （IIDT） after high complex anal fistula operation [J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2025, 14(01): 62-70.
[14]	Hong Ma, Yiqi Chen, Yixin Zhang, Yang Ren, Yuhui Cai, Lei Wang, Xinghua Zhu, Yi Zhang. Application of injectable platelet-rich fibrin combined with artificial dermis in treatment of chronic refractory wounds [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(10): 917-925.
[15]	Shan Shi, Zhigang Xu, Shuang Wei, Hao Guan, Jihong Shi. Advances in understanding of role of wound pathogens in wound healing and scar formation [J]. Chinese Journal of Clinicians(Electronic Edition), 2024, 18(10): 955-960.

Please choose a citation manager

Content to export