| Citation: | Wu RX,Shen JM,Duan FY,et al.Research progress on the application of stem cells and their derivatives in chronic wound repair[J].Chin J Burns Wounds,2026,42(9):896-902.DOI: 10.3760/cma.j.cn501225-20251110-00466. |
| [1] |
RodriguesM, KosaricN, BonhamCA, et al. Wound healing: a cellular perspective[J]. Physiol Rev, 2019,99(1):665-706. DOI: 10.1152/physrev.00067.2017.
|
| [2] |
中华医学会烧伤外科学分会, 《中华烧伤与创面修复杂志》编辑委员会. 慢性创面外用生长因子的临床专家共识(2025版)[J].中华烧伤与创面修复杂志,2025,41(8):711-724. DOI: 10.3760/cma.j.cn501225-20250426-00191.
|
| [3] |
PeñaOA, MartinP. Cellular and molecular mechanisms of skin wound healing[J]. Nat Rev Mol Cell Biol, 2024,25(8):599-616. DOI: 10.1038/s41580-024-00715-1.
|
| [4] |
PilkingtonSM, Bulfone-PausS, GriffithsC, et al. Inflammaging and the skin[J]. J Invest Dermatol, 2021,141(4Suppl):1087-1095. DOI: 10.1016/j.jid.2020.11.006.
|
| [5] |
EmingSA, MartinP, Tomic-CanicM. Wound repair and regeneration: mechanisms, signaling, and translation[J]. Sci Transl Med, 2014,6(265):265sr6. DOI: 10.1126/scitranslmed.3009337.
|
| [6] |
FahmaF, FirmandaA, CabralJ, et al. Three-dimensional printed cellulose for wound dressing applications[J]. 3D Print Addit Manuf, 2023,10(5):1015-1035. DOI: 10.1089/3dp.2021.0327.
|
| [7] |
HenryS, MapulaS, GreviousM, et al. Maximizing wound coverage in full-thickness skin defects: a randomized-controlled trial of autologous skin cell suspension and widely meshed autograft versus standard autografting[J]. J Trauma Acute Care Surg, 2024,96(1):85-93. DOI: 10.1097/TA.0000000000004120.
|
| [8] |
HoangDM, PhamPT, BachTQ, et al. Stem cell-based therapy for human diseases[J]. Signal Transduct Target Ther, 2022,7(1):272. DOI: 10.1038/s41392-022-01134-4.
|
| [9] |
RipponHJ, BishopAE. Embryonic stem cells[J]. Cell Prolif, 2004,37(1):23-34. DOI: 10.1111/j.1365-2184.2004.00298.x.
|
| [10] |
BellinM, MarchettoMC, GageFH, et al. Induced pluripotent stem cells: the new patient?[J]. Nat Rev Mol Cell Biol, 2012,13(11):713-726. DOI: 10.1038/nrm3448.
|
| [11] |
GoreckaJ, KostiukV, FereydooniA, et al. The potential and limitations of induced pluripotent stem cells to achieve wound healing[J]. Stem Cell Res Ther, 2019,10(1):87. DOI: 10.1186/s13287-019-1185-1.
|
| [12] |
CleversH. What is an adult stem cell?[J]. Science, 2015,350(6266):1319-1320. DOI: 10.1126/science.aad7016.
|
| [13] |
UraoN, LiuJ, TakahashiK, et al. Hematopoietic stem cells in wound healing response[J]. Adv Wound Care (New Rochelle), 2022,11(11):598-621. DOI: 10.1089/wound.2021.0065.
|
| [14] |
WagersAJ, WeissmanIL. Plasticity of adult stem cells[J]. Cell, 2004,116(5):639-648. DOI: 10.1016/s0092-8674(04)00208-9.
|
| [15] |
LiuW, ChenW, XieM, et al. Traumatic brain injury stimulates sympathetic tone-mediated bone marrow myelopoiesis to favor fracture healing[J]. Signal Transduct Target Ther, 2023,8(1):260. DOI: 10.1038/s41392-023-01457-w.
|
| [16] |
MannM, MehtaA, de BoerCG, et al. Heterogeneous responses of hematopoietic stem cells to inflammatory stimuli are altered with age[J]. Cell Rep, 2018,25(11):2992-3005.e5. DOI: 10.1016/j.celrep.2018.11.056.
|
| [17] |
QinY, GeG, YangP, et al. An update on adipose-derived stem cells for regenerative medicine: where challenge meets opportunity[J]. Adv Sci (Weinh), 2023,10(20):e2207334. DOI: 10.1002/advs.202207334.
|
| [18] |
PhinneyDG, Hwa LeeR, BoregowdaSV. Revisiting the mesenchymal "stem vs. stromal" cell dichotomy and its implications for development of improved potency metrics[J]. Stem Cells, 2023,41(5):444-452. DOI: 10.1093/stmcls/sxad019.
|
| [19] |
GalipeauJ, SensébéL. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities[J]. Cell Stem Cell, 2018,22(6):824-833. DOI: 10.1016/j.stem.2018.05.004.
|
| [20] |
KeatingA. Mesenchymal stromal cells: new directions[J]. Cell Stem Cell, 2012,10(6):709-716. DOI: 10.1016/j.stem.2012.05.015.
|
| [21] |
BiancoP, RobeyPG, SimmonsPJ. Mesenchymal stem cells: revisiting history, concepts, and assays[J]. Cell Stem Cell, 2008,2(4):313-319. DOI: 10.1016/j.stem.2008.03.002.
|
| [22] |
GaoF, ChiuSM, MotanDA, et al. Mesenchymal stem cells and immunomodulation: current status and future prospects[J]. Cell Death Dis, 2016,7(1):e2062. DOI: 10.1038/cddis.2015.327.
|
| [23] |
Aliniay-SharafshadehiS, YousefiMH, GhodratieM, et al. Exploring the therapeutic potential of different sources of mesenchymal stem cells: a novel approach to combat burn wound infections[J]. Front Microbiol, 2024,15:1495011. DOI: 10.3389/fmicb.2024.1495011.
|
| [24] |
AyavooT, MurugesanK, GnanasekaranA. Roles and mechanisms of stem cell in wound healing[J]. Stem Cell Investig, 2021,8:4. DOI: 10.21037/sci-2020-027.
|
| [25] |
WangY, FangJ, LiuB, et al. Reciprocal regulation of mesenchymal stem cells and immune responses[J]. Cell Stem Cell, 2022,29(11):1515-1530. DOI: 10.1016/j.stem.2022.10.001.
|
| [26] |
Ortiz-VirumbralesM, MentaR, PérezLM, et al. Human adipose mesenchymal stem cells modulate myeloid cells toward an anti-inflammatory and reparative phenotype: role of IL-6 and PGE2[J]. Stem Cell Res Ther, 2020,11(1):462. DOI: 10.1186/s13287-020-01975-2.
|
| [27] |
PourjafarM, SaidijamM, MansouriK, et al. All-trans retinoic acid preconditioning enhances proliferation, angiogenesis and migration of mesenchymal stem cell in vitro and enhances wound repair in vivo[J]. Cell Prolif, 2017,50(1):e12315.DOI: 10.1111/cpr.12315.
|
| [28] |
TamamaK, KerpedjievaSS. Acceleration of wound healing by multiple growth factors and cytokines secreted from multipotential stromal cells/mesenchymal stem cells[J]. Adv Wound Care (New Rochelle), 2012,1(4):177-182. DOI: 10.1089/wound.2011.0296.
|
| [29] |
WuY, ChenL, ScottPG, et al. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis[J]. Stem Cells, 2007,25(10):2648-2659. DOI: 10.1634/stemcells.2007-0226.
|
| [30] |
LiM, LuanF, ZhaoY, et al. Mesenchymal stem cell-conditioned medium accelerates wound healing with fewer scars[J]. Int Wound J, 2017,14(1):64-73. DOI: 10.1111/iwj.12551.
|
| [31] |
FarabiB, RosterK, HiraniR, et al. The efficacy of stem cells in wound healing: a systematic review[J]. Int J Mol Sci, 2024,25(5):3006. DOI: 10.3390/ijms25053006.
|
| [32] |
KrasnovaO, KovalevaA, SavelevaA, et al. Mesenchymal stem cells lose the senescent phenotype under 3D cultivation[J]. Stem Cell Res Ther, 2023,14(1):373. DOI: 10.1186/s13287-023-03599-8.
|
| [33] |
KimW, GwonY, ParkS, et al. Therapeutic strategies of three-dimensional stem cell spheroids and organoids for tissue repair and regeneration[J]. Bioact Mater, 2023,19:50-74. DOI: 10.1016/j.bioactmat.2022.03.039.
|
| [34] |
YangK, ParkHJ, HanS, et al. Recapitulation of in vivo-like paracrine signals of human mesenchymal stem cells for functional neuronal differentiation of human neural stem cells in a 3D microfluidic system[J]. Biomaterials, 2015,63:177-188. DOI: 10.1016/j.biomaterials.2015.06.011.
|
| [35] |
LeeJH, HanYS, LeeSH. Long-duration three-dimensional spheroid culture promotes angiogenic activities of adipose-derived mesenchymal stem cells[J]. Biomol Ther (Seoul), 2016,24(3):260-267. DOI: 10.4062/biomolther.2015.146.
|
| [36] |
Ohori-MoritaY, NiibeK, LimraksasinP, et al. Novel mesenchymal stem cell spheroids with enhanced stem cell characteristics and bone regeneration ability[J]. Stem Cells Transl Med, 2022,11(4):434-449. DOI: 10.1093/stcltm/szab030.
|
| [37] |
XiaoS, ZhaoT, WangJ, et al. Gelatin methacrylate (GelMA)-based hydrogels for cell transplantation: an effective strategy for tissue engineering[J]. Stem Cell Rev Rep, 2019,15(5):664-679. DOI: 10.1007/s12015-019-09893-4.
|
| [38] |
XiaS, WengT, JinR, et al. Curcumin-incorporated 3D bioprinting gelatin methacryloyl hydrogel reduces reactive oxygen species-induced adipose-derived stem cell apoptosis and improves implanting survival in diabetic wounds[J/OL]. Burns Trauma, 2022,10:tkac001[2025-11-10]. https://pubmed.ncbi.nlm.nih.gov/35291229/. DOI: 10.1093/burnst/tkac001.
|
| [39] |
WangP, HuangS, HuZ, et al. In situ formed anti-inflammatory hydrogel loading plasmid DNA encoding VEGF for burn wound healing[J]. Acta Biomater, 2019,100:191-201. DOI: 10.1016/j.actbio.2019.10.004.
|
| [40] |
ZhuY, LiaoY, ZhangY, et al. Novel nanofibrous membrane-supporting stem cell sheets for plasmid delivery and cell activation to accelerate wound healing[J]. Bioeng Transl Med, 2022,7(1):e10244. DOI: 10.1002/btm2.10244.
|
| [41] |
YangF, ChoSW, SonSM, et al. Genetic engineering of human stem cells for enhanced angiogenesis using biodegradable polymeric nanoparticles[J]. Proc Natl Acad Sci U S A, 2010,107(8):3317-3322. DOI: 10.1073/pnas.0905432106.
|
| [42] |
HendriksD, CleversH, ArtegianiB. CRISPR-cas tools and their application in genetic engineering of human stem cells and organoids[J]. Cell Stem Cell, 2020,27(5):705-731. DOI: 10.1016/j.stem.2020.10.014.
|
| [43] |
CressmanA, LeB, MoralesD, et al. Investigational new drug-enabling studies to use genetically modified mesenchymal stromal cells in patients with critical limb ischemia[J]. Stem Cells Transl Med, 2025,14(2):szae094. DOI: 10.1093/stcltm/szae094.
|
| [44] |
QiuY, YuB, JiangC, et al. Bone marrow mesenchymal stem cells overexpressing FGF-2 loaded onto a decellularized extracellular matrix hydrogel for the treatment of osteoarthritis[J]. Biomater Sci, 2026,14(1):9-30. DOI: 10.1039/d5bm00920k.
|
| [45] |
WangX, ZhaoT, HuangW, et al. Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors[J]. Stem Cells, 2009,27(12):3021-3031. DOI: 10.1002/stem.230.
|
| [46] |
SrifaW, KosaricN, AmorinA, et al. Cas9-AAV6-engineered human mesenchymal stromal cells improved cutaneous wound healing in diabetic mice[J]. Nat Commun, 2020,11(1):2470. DOI: 10.1038/s41467-020-16065-3.
|
| [47] |
PourfathMR, Behzad-BehbahaniA, HashemiSS, et al. Monitoring wound healing of burn in rat model using human Wharton's jelly mesenchymal stem cells containing cGFP integrated by lentiviral vectors[J]. Iran J Basic Med Sci, 2018,21(1):70-76. DOI: 10.22038/IJBMS.2017.19783.5212.
|
| [48] |
LiangW, BhatiaS, ReisbeckF, et al. Thermoresponsive hydrogels as microniches for growth and controlled release of induced pluripotent stem cells[J]. Adv Funct Mater, 2021,31:2010630. DOI: 10.1002/adfm.202010630.
|
| [49] |
ErP, ZhangZ, ChenY, et al. ROS-scavenging hybrid hydrogel for genetically engineered stem cell delivery and limb ischemia therapy[J]. Chem Eng J, 2021,425:131504. DOI: 10.1016/j.cej.2021.131504.
|
| [50] |
HanZ, YuanM, LiuL, et al. pH-responsive wound dressings: advances and prospects[J]. Nanoscale Horiz, 2023,8(4):422-440. DOI: 10.1039/d2nh00574c.
|
| [51] |
ZhouL, ZengZ, LiuS, et al. Multifunctional DNA hydrogel enhances stemness of adipose-derived stem cells to activate immune pathways for guidance burn wound regeneration[J]. Adv Funct Mater, 2022,32:2207466. DOI: 10.1002/adfm.202207466.
|
| [52] |
ZhangQ, LiJ, JiaJ, et al. Topology scaffolds-enhanced paracrine of BMSCs through mechanotransduction-related metabolism reprogramming for burn wounds healing[J]. Biomaterials, 2026,324:123518. DOI: 10.1016/j.biomaterials.2025.123518.
|
| [53] |
DingJY, ChenMJ, WuLF, et al. Mesenchymal stem cell-derived extracellular vesicles in skin wound healing: roles, opportunities and challenges[J]. Mil Med Res, 2023,10(1):36. DOI: 10.1186/s40779-023-00472-w.
|
| [54] |
RezaieJ, FeghhiM, EtemadiT. A review on exosomes application in clinical trials: perspective, questions, and challenges[J]. Cell Commun Signal, 2022,20(1):145. DOI: 10.1186/s12964-022-00959-4.
|
| [55] |
WangP, TheocharidisG, VlachosIS, et al. Exosomes derived from epidermal stem cells improve diabetic wound healing[J]. J Invest Dermatol, 2022,142(9):2508-2517.e13. DOI: 10.1016/j.jid.2022.01.030.
|
| [56] |
SongY, YouY, XuX, 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. DOI: 10.1002/advs.202304023.
|
| [57] |
LiJ, GaoH, XiongY, et al. Enhancing cutaneous wound healing based on human induced neural stem cell-derived exosomes[J]. Int J Nanomedicine, 2022,17:5991-6006. DOI: 10.2147/IJN.S377502.
|
| [58] |
RenH, SuP, ZhaoF, et al. Adipose mesenchymal stem cell-derived exosomes promote skin wound healing in diabetic mice by regulating epidermal autophagy[J/OL]. Burns Trauma, 2024,12:tkae001[2025-11-10]. https://pubmed.ncbi.nlm.nih.gov/38434722/. DOI: 10.1093/burnst/tkae001.
|
| [59] |
HerrmannIK, WoodM, FuhrmannG. Extracellular vesicles as a next-generation drug delivery platform[J]. Nat Nanotechnol, 2021,16(7):748-759. DOI: 10.1038/s41565-021-00931-2.
|
| [60] |
HeL, ZhuC, JiaJ, et al. ADSC-Exos containing MALAT1 promotes wound healing by targeting miR-124 through activating Wnt/β-catenin pathway[J]. Biosci Rep, 2020,40(5):BSR20192549. DOI: 10.1042/BSR20192549.
|
| [61] |
HuN, CaiZ, JiangX, et al. Hypoxia-pretreated ADSC-derived exosome-embedded hydrogels promote angiogenesis and accelerate diabetic wound healing[J]. Acta Biomater, 2023,157:175-186. DOI: 10.1016/j.actbio.2022.11.057.
|
| [62] |
LiC, LiX, ShiZ, et al. Exosomes from LPS-preconditioned bone marrow MSCs accelerated peripheral nerve regeneration via M2 macrophage polarization: involvement of TSG-6/NF-κB/NLRP3 signaling pathway[J]. Exp Neurol, 2022,356:114139. DOI: 10.1016/j.expneurol.2022.114139.
|
| [63] |
WangJ, WuH, PengY, et al. Hypoxia adipose stem cell-derived exosomes promote high-quality healing of diabetic wound involves activation of PI3K/Akt pathways[J]. J Nanobiotechnology, 2021,19(1):202. DOI: 10.1186/s12951-021-00942-0.
|
| [64] |
ChuZ, HuangQ, MaK, et al. Novel neutrophil extracellular trap-related mechanisms in diabetic wounds inspire a promising treatment strategy with hypoxia-challenged small extracellular vesicles[J]. Bioact Mater, 2023,27:257-270. DOI: 10.1016/j.bioactmat.2023.04.007.
|
| [65] |
LiL, WangF, ZhuD, et al. Engineering exosomes and exosome-like nanovesicles for improving tissue targeting and retention[J]. Fundam Res, 2025,5(2):851-867. DOI: 10.1016/j.fmre.2024.03.025.
|
| [66] |
YangJ, WuS, HeM. Engineered exosome-based senolytic therapy alleviates stroke by targeting p21+CD86+ microglia[J]. Exploration (Beijing), 2025,5(3):20240349. DOI: 10.1002/EXP.20240349.
|
| [67] |
YangQ, LiS, OuH, et al. Exosome-based delivery strategies for tumor therapy: an update on modification, loading, and clinical application[J]. J Nanobiotechnology, 2024,22(1):41. DOI: 10.1186/s12951-024-02298-7.
|
| [68] |
WanT, ZhongJ, PanQ, et al. Exosome-mediated delivery of Cas9 ribonucleoprotein complexes for tissue-specific gene therapy of liver diseases[J]. Sci Adv, 2022,8(37):eabp9435. DOI: 10.1126/sciadv.abp9435.
|
| [69] |
JafarH, AlmousaR, AlhawariH, et al. Human umbilical cord mesenchymal stromal cells derivatives in treating diabetic foot ulcers: a phase I/II safety and efficacy trial[J]. Stem Cell Res Ther, 2025,16(1):657. DOI: 10.1186/s13287-025-04736-1.
|
| [70] |
ZhouC, ZhangB, YangY, et al. Stem cell-derived exosomes: emerging therapeutic opportunities for wound healing[J]. Stem Cell Res Ther, 2023,14(1):107. DOI: 10.1186/s13287-023-03345-0.
|