细胞治疗与创面修复

刘琰; 刘欣盈

doi:10.3760/cma.j.cn501225-20240108-00009

细胞治疗与创面修复

doi: 10.3760/cma.j.cn501225-20240108-00009

刘琰^,,
刘欣盈

上海交通大学医学院附属瑞金医院灼伤整形科，上海　　200025

基金项目:

国家自然科学基金面上项目 82072173, 82172199, 82272262

上海市生物医药领域定向项目 22DX1900600

上海市重中之重研究中心项目 2023ZZ02013

上海市临床重点专科项目 shslczdzk02302

详细信息

通讯作者:
刘琰，Email：rjliuyan@126.com

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- 被引次数: 0
出版历程
- 收稿日期: 2024-01-08

Cell therapy and wound repair

Liu Yan^,,
Liu Hsinying

Department of Burn, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China

Funds:

General Program of National Natural Science Foundation of China 82072173, 82172199, 82272262

Shanghai Directed Projects of Biopharmaceutical Field 22DX1900600

Shanghai Research Center for Burn and Wound Repair 2023ZZ02013

Shanghai Municipal Key Clinical Specialty of China shslczdzk02302

More Information

Corresponding author: Liu Yan, Email: rjliuyan@126.com

摘要

摘要: 细胞治疗包括以活细胞为基础的治疗手段和以细胞外囊泡及生物活性分子为主的细胞衍生物治疗方法。细胞治疗作为近年研究热点，是解决难愈创面修复这一临床难题的潜在可行策略。材料科学和细胞生物学的快速发展拉开了细胞治疗的新序幕，同时也提出了如何进一步优化细胞治疗并将其应用于创面修复的新命题。该文回顾了用于创面治疗的细胞类型，汇总了基于细胞治疗新技术的应用和探索，梳理了现有细胞治疗临床应用的困境，并展望了创面修复中细胞治疗的发展趋势，以期促进创新性细胞治疗体系的发展，进一步提高创面临床治疗效果。
- 细胞生物学 /
- 胞外囊泡 /
- 细胞治疗 /
- 创面修复 /
- 细胞递送
Abstract: Cell therapy includes living cell-based therapy and cell-derivative therapy that is based on extracellular vesicles and bioactive molecules. As a research hotspot in recent years, cell therapy is a potential strategy to solve the clinical problem of refractory wound repair. The rapid development of material science and cell biology has opened a new prelude to cell therapy, and at the same time, puts forward a new proposition on how to further optimize and apply cell therapy to wound repair. This article reviewed the cell types used for wound treatment, summarized the application and exploration of cell therapy-based new technologies, sorted out the difficulties in the clinical application of existing cell therapies, and looked into the future development trend of cell therapy for wound repair, in order to promote the development of innovative cell therapy system and further improve the clinical wound treatment effect.
- Cell biology /
- Extracellular vesicles /
- Cell therapy /
- Wound repair /
- Cell delivery
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参考文献(75)

[1]	RheinwaldJG, GreenH. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells[J]. Cell, 1975,6(3):331-343. DOI: 10.1016/s0092-8674(75)80001-8.
[2]	GreenH, KehindeO, ThomasJ. Growth of cultured human epidermal cells into multiple epithelia suitable for grafting[J]. Proc Natl Acad Sci U S A, 1979,76(11):5665-5668. DOI: 10.1073/pnas.76.11.5665.
[3]	Grafting of burns with cultured epithelium prepared from autologous epidermal cells[J]. Lancet, 1981,1(8211):75-78.
[4]	AtiyehBS, CostagliolaM. Cultured epithelial autograft (CEA) in burn treatment: three decades later[J]. Burns, 2007,33(4):405-413. DOI: 10.1016/j.burns.2006.11.002.
[5]	AllouniA, PapiniR, LewisD. Spray-on-skin cells in burns: a common practice with no agreed protocol[J]. Burns, 2013,39(7):1391-1394. DOI: 10.1016/j.burns.2013.03.017.
[6]	Cooper-JonesB, VisintiniS. A noncultured autologous skin cell spray graft for the treatment of burns [M]. Ottawa (ON): Canadian Agency for Drugs and Technologies in Health, 2016:1-11.
[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]	LoCH, ChongE, AkbarzadehS, et al. A systematic review: current trends and take rates of cultured epithelial autografts in the treatment of patients with burn injuries[J]. Wound Repair Regen, 2019,27(6):693-701. DOI: 10.1111/wrr.12748.
[9]	Ortega-ZilicN, HunzikerT, LäuchliS, et al. EpiDex ^® Swiss field trial 2004-2008[J]. Dermatology, 2010,221(4):365-372. DOI: 10.1159/000321333.
[10]	CoulombB, FriteauL, BaruchJ, et al. Advantage of the presence of living dermal fibroblasts within in vitro reconstructed skin for grafting in humans[J]. Plast Reconstr Surg, 1998,101(7):1891-1903. DOI: 10.1097/00006534-199806000-00018.
[11]	ShamsF, RahimpourA, VahidnezhadH, et al. The utility of dermal fibroblasts in treatment of skin disorders: a paradigm of recessive dystrophic epidermolysis bullosa[J]. Dermatol Ther, 2021,34(4):e15028. DOI: 10.1111/dth.15028.
[12]	LammeEN, Van LeeuwenRT, BrandsmaK, et al. Higher numbers of autologous fibroblasts in an artificial dermal substitute improve tissue regeneration and modulate scar tissue formation[J]. J Pathol, 2000,190(5):595-603. DOI: 10.1002/(SICI)1096-9896(200004)190:5<595::AID-PATH572>3.0.CO;2-V.
[13]	SteiglitzBM, MaherRJ, GratzKR, et al. The viable bioengineered allogeneic cellularized construct StrataGraft ^® synthesizes, deposits, and organizes human extracellular matrix proteins into tissue type-specific structures and secretes soluble factors associated with wound healing[J]. Burns, 2024,50(2):424-432. DOI: 10.1016/j.burns.2023.06.001.
[14]	CaiS, PanY, HanB, et al. Transplantation of human bone marrow-derived mesenchymal stem cells transfected with ectodysplasin for regeneration of sweat glands[J]. Chin Med J (Engl), 2011,124(15):2260-2268.
[15]	Castro-ManrrezaME, MontesinosJJ. Immunoregulation by mesenchymal stem cells: biological aspects and clinical applications[J]. J Immunol Res, 2015,2015:394917. DOI: 10.1155/2015/394917.
[16]	BronckaersA, HilkensP, MartensW, et al. Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis[J]. Pharmacol Ther, 2014,143(2):181-196. DOI: 10.1016/j.pharmthera.2014.02.013.
[17]	Guillamat-PratsR. The role of MSC in wound healing, scarring and regeneration[J]. Cells, 2021, 10(7):1729. DOI: 10.3390/cells10071729.
[18]	LiubaviciuteA, IvaskieneT, BiziulevicieneG. Modulated mesenchymal stromal cells improve skin wound healing[J]. Biologicals, 2020,67:1-8. DOI: 10.1016/j.biologicals.2020.08.003.
[19]	FalangaV, IwamotoS, ChartierM, et al. Autologous bone marrow-derived cultured mesenchymal stem cells delivered in a fibrin spray accelerate healing in murine and human cutaneous wounds[J]. Tissue Eng, 2007, 13(6): 1299-1312. DOI: 10.1089/ten.2006.0278.
[20]	CloverAJ, KumarAH, IsaksonM, et al. Allogeneic mesenchymal stem cells, but not culture modified monocytes, improve burn wound healing[J]. Burns, 2015,41(3):548-557. DOI: 10.1016/j.burns.2014.08.009.
[21]	LuD, ChenB, LiangZ, et al. Comparison of bone marrow mesenchymal stem cells with bone marrow-derived mononuclear cells for treatment of diabetic critical limb ischemia and foot ulcer: a double-blind, randomized, controlled trial[J]. Diabetes Res Clin Pract, 2011,92(1):26-36. DOI: 10.1016/j.diabres.2010.12.010.
[22]	LatailladeJJ, DoucetC, BeyE, et al. New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy[J]. Regen Med, 2007,2(5):785-794. DOI: 10.2217/17460751.2.5.785.
[23]	WettsteinR, SavicM, PiererG, et al. Progenitor cell therapy for sacral pressure sore: a pilot study with a novel human chronic wound model[J]. Stem Cell Res Ther, 2014,5(1):18. DOI: 10.1186/scrt407.
[24]	SongY, ZhaoHY, LyuZS, et al. Dysfunctional bone marrow mesenchymal stem cells in patients with poor graft function after allogeneic hematopoietic stem cell transplantation[J]. Biol Blood Marrow Transplant, 2018,24(10):1981-1989. DOI: 10.1016/j.bbmt.2018.06.021.
[25]	LevyO, KuaiR, SirenE, et al. Shattering barriers toward clinically meaningful MSC therapies[J]. Sci Adv, 2020,6(30):eaba6884. DOI: 10.1126/sciadv.aba6884.
[26]	FuX, FangL, LiX, et al. Enhanced wound-healing quality with bone marrow mesenchymal stem cells autografting after skin injury[J]. Wound Repair Regen, 2006,14(3):325-335. DOI: 10.1111/j.1743-6109.2006.00128.x.
[27]	TakahashiK, YamanakaS. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors[J]. Cell, 2006,126(4):663-676. DOI: 10.1016/j.cell.2006.07.024.
[28]	TanabeK, NakamuraM, NaritaM, et al. Maturation, not initiation, is the major roadblock during reprogramming toward pluripotency from human fibroblasts[J]. Proc Natl Acad Sci U S A, 2013,110(30):12172-12179. DOI: 10.1073/pnas.1310291110.
[29]	BilousovaG, ChenJ, RoopDR. Differentiation of mouse induced pluripotent stem cells into a multipotent keratinocyte lineage[J]. J Invest Dermatol, 2011,131(4):857-864. DOI: 10.1038/jid.2010.364.
[30]	ItohM, Umegaki-AraoN, GuoZ, et al. Generation of 3D skin equivalents fully reconstituted from human induced pluripotent stem cells (iPSCs)[J]. PLoS One, 2013,8(10):e77673. DOI: 10.1371/journal.pone.0077673.
[31]	MartinPE, O'ShaughnessyEM, WrightCS, et al. The potential of human induced pluripotent stem cells for modelling diabetic wound healing in vitro[J]. Clin Sci (Lond), 2018,132(15):1629-1643. DOI: 10.1042/CS20171483.
[32]	WuR, DuD, BoY, et al. Hsp90α promotes the migration of iPSCs-derived keratinocyte to accelerate deep second-degree burn wound healing in mice[J]. Biochem Biophys Res Commun, 2019,520(1):145-151. DOI: 10.1016/j.bbrc.2019.09.120.
[33]	YanY, JiangJ, ZhangM, et al. Effect of iPSCs-derived keratinocytes on healing of full-thickness skin wounds in mice[J]. Exp Cell Res, 2019,385(1):111627. DOI: 10.1016/j.yexcr.2019.111627.
[34]	ShenYI, ChoH, PapaAE, et al. Engineered human vascularized constructs accelerate diabetic wound healing[J]. Biomaterials, 2016,102:107-119. DOI: 10.1016/j.biomaterials.2016.06.009.
[35]	AguiarC, TherrienJ, LemireP, et al. Differentiation of equine induced pluripotent stem cells into a keratinocyte lineage[J]. Equine Vet J, 2016,48(3):338-345. DOI: 10.1111/evj.12438.
[36]	TapiaN, SchölerHR. Molecular obstacles to clinical translation of iPSCs[J]. Cell Stem Cell, 2016,19(3):298-309. DOI: 10.1016/j.stem.2016.06.017.
[37]	Álvaro-AfonsoFJ, Sanz-CorbalánI, Lázaro-MartínezJL, et al. Adipose-derived mesenchymal stem cells in the treatment of diabetic foot ulcers: a review of preclinical and clinical studies[J]. Angiology, 2020,71(9):853-863. DOI: 10.1177/0003319720939467.
[38]	SurowieckaA, StrużynaJ. Adipose-derived stem cells for facial rejuvenation[J]. J Pers Med, 2022,12(1):117. DOI: 10.3390/jpm12010117.
[39]	Abou EittaRS, IsmailAA, AbdelmaksoudRA, et al. Evaluation of autologous adipose-derived stem cells vs. fractional carbon dioxide laser in the treatment of post acne scars: a split-face study[J]. Int J Dermatol, 2019, 58(10): 1212-1222. DOI: 10.1111/ijd.14567.
[40]	IacomiDM, RoscaAM, TutuianuR, et al. Generation of an immortalized human adipose-derived mesenchymal stromal cell line suitable for wound healing therapy[J]. Int J Mol Sci, 2022,23 (16):8925. DOI: 10.3390/ijms23168925.
[41]	ZhangCP, FuXB. Therapeutic potential of stem cells in skin repair and regeneration[J]. Chin J Traumatol, 2008,11(4):209-221. DOI: 10.1016/s1008-1275(08)60045-0.
[42]	SchrederA, PierardGE, PaquetP, et al. Facing towards epidermal stem cells (Review)[J]. Int J Mol Med, 2010,26(2):171-174. DOI: 10.3892/ijmm_00000449.
[43]	CattaneoC, EnzoE, De RosaL, et al. Allele-specific CRISPR-Cas9 editing of dominant epidermolysis bullosa simplex in human epidermal stem cells[J]. Mol Ther, 2024,32(2):372-383. DOI: 10.1016/j.ymthe.2023.11.027.
[44]	YangGN, StrudwickXL, BonderC, et al. Effect of flightless I expression on epidermal stem cell niche during wound repair[J]. Adv Wound Care (New Rochelle), 2020,9(4):161-173. DOI: 10.1089/wound.2018.0884.
[45]	LimatA, MauriD, HunzikerT. Successful treatment of chronic leg ulcers with epidermal equivalents generated from cultured autologous outer root sheath cells[J]. J Invest Dermatol, 1996,107(1):128-135. DOI: 10.1111/1523-1747.ep12298415.
[46]	YangR, WangJ, ZhouZ, et al. Role of caveolin-1 in epidermal stem cells during burn wound healing in rats[J]. Dev Biol, 2019,445(2):271-279. DOI: 10.1016/j.ydbio.2018.11.015.
[47]	BabakhaniA, HashemiP, Mohajer AnsariJ, et al. In vitro differentiation of hair follicle stem cell into keratinocyte by simvastatin[J]. Iran Biomed J, 2019,23(6):404-411. DOI: 10.29252/ibj.23.6.404.
[48]	SamiecM, WiaterJ, WartalskiK, et al. The relative abundances of human leukocyte antigen-E, α-galactosidase a and α-gal antigenic determinants are biased by trichostatin a-dependent epigenetic transformation of triple-transgenic pig-derived dermal fibroblast cells[J]. Int J Mol Sci, 2022,23 (18):10296.DOI: 10.3390/ijms231810296.
[49]	HouP, LiY, ZhangX, et al. Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds[J]. Science, 2013,341(6146):651-654. DOI: 10.1126/science.1239278.
[50]	GuanJ, WangG, WangJ, et al. Chemical reprogramming of human somatic cells to pluripotent stem cells[J]. Nature, 2022,605(7909):325-331. DOI: 10.1038/s41586-022-04593-5.
[51]	BurmeisterDM, StoneR, WriceN, et al. Delivery of allogeneic adipose stem cells in polyethylene glycol-fibrin hydrogels as an adjunct to meshed autografts after sharp debridement of deep partial thickness burns[J]. Stem Cells Transl Med, 2018,7(4):360-372. DOI: 10.1002/sctm.17-0160.
[52]	ChenJ, LiuY, ZhangJ, et al. External application of human umbilical cord-derived mesenchymal stem cells in hyaluronic acid gel repairs foot wounds of types I and Ⅱ diabetic rats through paracrine action mode[J]. Stem Cells Transl Med, 2023,12(10):689-706. DOI: 10.1093/stcltm/szad050.
[53]	BaiH, Kyu-CheolN, WangZ, et al. Regulation of inflammatory microenvironment using a self-healing hydrogel loaded with BM-MSCs for advanced wound healing in rat diabetic foot ulcers[J]. J Tissue Eng, 2020,11:2041731420947242. DOI: 10.1177/2041731420947242.
[54]	BelloYM, FalabellaAF, EaglsteinWH. Tissue-engineered skin. Current status in wound healing [J]. Am J Clin Dermatol, 2001, 2(5): 305-313.
[55]	CrawfordL, WyattM, BryersJ, et al. Biocompatibility evolves: phenomenology to toxicology to regeneration[J]. Adv Healthc Mater, 2021,10(11):e2002153. DOI: 10.1002/adhm.202002153.
[56]	ZhangJ, WehrleE, RubertM, et al. 3D bioprinting of human tissues: biofabrication, bioinks, and bioreactors[J]. Int J Mol Sci, 2021,22(8):3971. DOI: 10.3390/ijms22083971.
[57]	SawyerSW, TakedaK, AlayoubiA, et al. 3D bioprinting optimization of human mesenchymal stromal cell laden gelatin-alginate-collagen bioink[J]. Biomed Mater, 2022,18(1).DOI: 10.1088/1748-605X/aca3e7.
[58]	BaltazarT, JiangB, MoncayoA, et al. 3D bioprinting of an implantable xeno-free vascularized human skin graft[J]. Bioeng Transl Med, 2023,8(1):e10324. DOI: 10.1002/btm2.10324.
[59]	WuY, LiangT, HuY, et al. 3D bioprinting of integral ADSCs-NO hydrogel scaffolds to promote severe burn wound healing[J]. Regen Biomater, 2021,8(3):rbab014. DOI: 10.1093/rb/rbab014.
[60]	HaoL, TaoX, FengM, et al. Stepwise multi-cross-linking bioink for 3D embedded bioprinting to promote full-thickness wound healing[J]. ACS Appl Mater Interfaces, 2023,15(20):24034-24046. DOI: 10.1021/acsami.3c00688.
[61]	FerroniL, D'AmoraU, GardinC, et al. Stem cell-derived small extracellular vesicles embedded into methacrylated hyaluronic acid wound dressings accelerate wound repair in a pressure model of diabetic ulcer[J]. J Nanobiotechnology, 2023,21(1):469. DOI: 10.1186/s12951-023-02202-9.
[62]	LiM, SunL, LiuZ, et al. 3D bioprinting of heterogeneous tissue-engineered skin containing human dermal fibroblasts and keratinocytes[J]. Biomater Sci, 2023,11(7):2461-2477. DOI: 10.1039/d2bm02092k.
[63]	FuH, ZhangD, ZengJ, et al. Application of 3D-printed tissue-engineered skin substitute using innovative biomaterial loaded with human adipose-derived stem cells in wound healing[J]. Int J Bioprint, 2023,9(2):674. DOI: 10.18063/ijb.v9i2.674.
[64]	XueK, JiangY, ZhangX, et al. Hypoxic ADSCs-derived EVs promote the proliferation and chondrogenic differentiation of cartilage stem/progenitor cells[J]. Adipocyte, 2021,10(1):322-337. DOI: 10.1080/21623945.2021.1945210.
[65]	ZhangJ, ZhangJ, JiangX, et al. ASCs-EVs inhibit apoptosis and promote myocardial function in the infarcted heart via miR-221[J]. Discov Med, 2023,35(179):1077-1085. DOI: 10.24976/Discov.Med.202335179.104.
[66]	JinJ, ShiY, GongJ, et al. Exosome secreted from adipose-derived stem cells attenuates diabetic nephropathy by promoting autophagy flux and inhibiting apoptosis in podocyte[J]. Stem Cell Res Ther, 2019,10(1):95. DOI: 10.1186/s13287-019-1177-1.
[67]	DrommelschmidtK, SerdarM, BendixI, et al. Mesenchymal stem cell-derived extracellular vesicles ameliorate inflammation-induced preterm brain injury[J]. Brain Behav Immun, 2017,60:220-232. DOI: 10.1016/j.bbi.2016.11.011.
[68]	PatelNJ, AshrafA, ChungEJ. Extracellular vesicles as regulators of the extracellular matrix[J]. Bioengineering (Basel), 2023,10(2):136.DOI: 10.3390/bioengineering10020136.
[69]	WolfM, PoupardinRW, Ebner-PekingP, et al. A functional corona around extracellular vesicles enhances angiogenesis, skin regeneration and immunomodulation[J]. J Extracell Vesicles, 2022,11(4):e12207. DOI: 10.1002/jev2.12207.
[70]	ZhangW, WangT, XueY, et al. Research progress of extracellular vesicles and exosomes derived from mesenchymal stem cells in the treatment of oxidative stress-related diseases[J]. Front Immunol, 2023,14:1238789. DOI: 10.3389/fimmu.2023.1238789.
[71]	ShiR, JinY, ZhaoS, et al. Hypoxic ADSC-derived exosomes enhance wound healing in diabetic mice via delivery of circ-Snhg11 and induction of M2-like macrophage polarization[J]. Biomed Pharmacother, 2022,153:113463. DOI: 10.1016/j.biopha.2022.113463.
[72]	曹涛, 郝彤, 肖丹, 等. 人脂肪干细胞外泌体对糖尿病周围神经病变的作用及其机制[J]. 中华烧伤与创面修复杂志, 2024, 40(3): 240-248. DOI: 10.3760/cma.j.cn501225-20231207-00230.
[73]	XiangQ, XiaoJ, ZhangH, et al. Preparation and characterisation of bFGF-encapsulated liposomes and evaluation of wound-healing activities in the rat[J]. Burns, 2011,37(5):886-895. DOI: 10.1016/j.burns.2011.01.018.
[74]	WangC, WangM, XuT, et al. Engineering bioactive self-healing antibacterial exosomes hydrogel for promoting chronic diabetic wound healing and complete skin regeneration[J]. Theranostics, 2019,9(1):65-76. DOI: 10.7150/thno.29766.
[75]	何佳, 王婧薷, 甘文军, 等. 单细胞RNA测序解析普通小鼠和糖尿病小鼠全层皮肤缺损创面中CD34 ⁺细胞的类型与功能[J]. 中华烧伤与创面修复杂志, 2024, 40(3): 230-239. DOI: 10.3760/cma.j.cn501225-20231130-00217.