Research progress of induced pluripotent stem cells in promoting wound healing of diabetic foot ulcers
-
摘要: 糖尿病足溃疡等慢性创伤在人群中广泛流行,给患者和社会都带来了巨大的负担。而在现有的治疗方式下,糖尿病足溃疡往往愈合不良且容易复发,因此找寻新型疗法显得尤为迫切和重要。干细胞疗法作为一种新兴的治疗方式,其在糖尿病足溃疡愈合中的作用已得到大量基础和临床研究的证实。然而,由于获取干细胞往往依赖于侵入性手段,免疫排斥和移植后的细胞存活率低等问题也限制了干细胞疗法的大规模应用和推广。近年来,随着诱导多能干细胞(iPSC)技术的发展和进步,其在糖尿病足溃疡的治疗中表现出很强的转化潜能。该文将围绕iPSC在包括糖尿病溃疡和肢体缺血在内的创伤愈合动物模型中的应用及前景、临床应用的局限性和改善安全性的方法展开综述。Abstract: Chronic wounds such as diabetic foot ulcers are epidemic, which bring huge burdens to both the patients and the society. However, with current treatment methods, diabetic foot ulcers often heal poorly and recur frequently, so it is urgent and important to find new and advanced therapies. Stem cell therapy has been proved by a large number of pre-clinical and clinical studies as a potential treatment for chronic wounds. However, the acquisition of stem cells often depends on invasive techniques, and immunogenicity and limited cell survival in vivo also limit the large-scale application and promotion of stem cell therapy. In the recent years, with the development and advance of induced pluripotent stem cell (iPSC) technology, it has shown a strong translational potential in the treatment of chronic wounds such as diabetic foot ulcers. This article reviews the applications and prospect of iPSCs in animal wound healing models including diabetic ulcers and limb ischemia, the limitations of their clinical application, and the methods to improve their safety.
-
Key words:
- Diabetic foot /
- Ulcer /
- Induced pluripotent stem cells /
- Stem cell transplantation /
- Wound repair
-
[1] YuQ, QiaoGH, WangM, et al. Stem cell-based therapy for diabetic foot ulcers[J]. Front Cell Dev Biol, 2022,10:812262. DOI: 10.3389/fcell.2022.812262. [2] DoğruelH, AydemirM, BalciMK. Management of diabetic foot ulcers and the challenging points: an endocrine view[J]. World J Diabetes, 2022,13(1):27-36. DOI: 10.4239/wjd.v13.i1.27. [3] HollJ, KowalewskiC, ZimekZ, et al. Chronic diabetic wounds and their treatment with skin substitutes[J]. Cells, 2021,10(3):655. DOI: 10.3390/cells10030655. [4] TheocharidisG, ThomasBE, SarkarD, et al. Single cell transcriptomic landscape of diabetic foot ulcers[J]. Nat Commun, 2022,13(1):181. DOI: 10.1038/s41467-021-27801-8. [5] WangA, LvG, ChengX, et al. Guidelines on multidisciplinary approaches for the prevention and management of diabetic foot disease (2020 edition)[J/OL]. Burns Trauma, 2020, 8:tkaa017[2022-04-01]. https://pubmed.ncbi.nlm.nih.gov/32685563/. DOI: 10.1093/burnst/tkaa017. [6] JiS, LiuX, HuangJ, et al. Consensus on the application of negative pressure wound therapy of diabetic foot wounds[J/OL]. Burns Trauma, 2021, 9:tkab018[2022-04-02]. https://pubmed.ncbi.nlm.nih.gov/34212064/.DOI: 10.1093/burnst/tkab018. [7] JeffcoateWJ, VileikyteL, BoykoEJ, et al. Current challenges and opportunities in the prevention and management of diabetic foot ulcers[J]. Diabetes Care, 2018,41(4):645-52. DOI: 10.2337/dc17-1836. [8] BuchadeS, DesaiS, BhondeR, et al. Stem cells: a golden therapy for diabetic wounds[J]. Curr Diabetes Rev, 2021,17(2):156-160. DOI: 10.2174/1573399816666200716200450. [9] CaoY, GangX, SunC, et al. Mesenchymal stem cells improve healing of diabetic foot ulcer[J]. J Diabetes Res, 2017,2017:9328347. DOI: 10.1155/2017/9328347. [10] XuSM, LiangT. Clinical observation of the application of autologous peripheral blood stem cell transplantation for the treatment of diabetic foot gangrene[J]. Exp Ther Med, 2016,11(1):283-288. DOI: 10.3892/etm.2015.2888. [11] FooJB, LooiQH, ChongPP, et al. Comparing the therapeutic potential of stem cells and their secretory products in regenerative medicine[J]. Stem Cells Int, 2021,2021:2616807. DOI: 10.1155/2021/2616807. [12] 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. [13] TakahashiK, TanabeK, OhnukiM, et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors[J]. Cell, 2007,131(5):861-872. DOI: 10.1016/j.cell.2007.11.019. [14] 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. [15] HaridhasapavalanKK, BorgohainMP, DeyC, et al. An insight into non-integrative gene delivery approaches to generate transgene-free induced pluripotent stem cells[J]. Gene, 2019,686:146-159. DOI: 10.1016/j.gene.2018.11.069. [16] LopesL, SetiaO, AurshinaA, et al. Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research[J]. Stem Cell Res Ther, 2018,9(1):188. DOI: 10.1186/s13287-018-0938-6. [17] SinghVK, KalsanM, KumarN, et al. Induced pluripotent stem cells: applications in regenerative medicine, disease modeling, and drug discovery[J]. Front Cell Dev Biol, 2015,3:2. DOI: 10.3389/fcell.2015.00002. [18] ClaytonZE, TanRP, MiravetMM, et al. Induced pluripotent stem cell-derived endothelial cells promote angiogenesis and accelerate wound closure in a murine excisional wound healing model[J]. Biosci Rep, 2018,38(4):BSR20180563. DOI: 10.1042/BSR20180563. [19] WangAYL. Human induced pluripotent stem cell-derived exosomes as a new therapeutic strategy for various diseases[J]. Int J Mol Sci, 2021,22(4):1769. DOI: 10.3390/ijms22041769. [20] LiuX, LiQ, NiuX, et al. Exosomes secreted from human-induced pluripotent stem cell-derived mesenchymal stem cells prevent osteonecrosis of the femoral head by promoting angiogenesis[J]. Int J Biol Sci, 2017,13(2):232-244. DOI: 10.7150/ijbs.16951. [21] 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. [22] ChoudhuryS, SurendranN, DasA. Recent advances in the induced pluripotent stem cell-based skin regeneration[J]. Wound Repair Regen, 2021,29(5):697-710. DOI: 10.1111/wrr.12925. [23] HoffmannD, SchottJW, GeisFK, et al. Detailed comparison of retroviral vectors and promoter configurations for stable and high transgene expression in human induced pluripotent stem cells[J]. Gene Ther, 2017,24(5):298-307. DOI: 10.1038/gt.2017.20. [24] JohnsonWE. Origins and evolutionary consequences of ancient endogenous retroviruses[J]. Nat Rev Microbiol, 2019,17(6):355-370. DOI: 10.1038/s41579-019-0189-2. [25] 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. [26] KaushikK, DasA. Endothelial progenitor cell therapy for chronic wound tissue regeneration[J]. Cytotherapy, 2019,21(11):1137-1150. DOI: 10.1016/j.jcyt.2019.09.002. [27] KimKL, SongSH, ChoiKS, et al. Cooperation of endothelial and smooth muscle cells derived from human induced pluripotent stem cells enhances neovascularization in dermal wounds[J]. Tissue Eng Part A, 2013,19(21/22):2478-2485. DOI: 10.1089/ten.TEA.2012.0768. [28] DashBC, XuZ, LinL, et al. Stem cells and engineered scaffolds for regenerative wound healing[J]. Bioengineering (Basel), 2018,5(1):23. DOI: 10.3390/bioengineering5010023. [29] JanuszykM, ChenK, HennD, et al. Characterization of diabetic and non-diabetic foot ulcers using single-cell RNA-sequencing[J]. Micromachines (Basel), 2020,11(9):815. DOI: 10.3390/mi11090815. [30] KashpurO, SmithA, Gerami-NainiB, et al. Differentiation of diabetic foot ulcer-derived induced pluripotent stem cells reveals distinct cellular and tissue phenotypes[J]. FASEB J, 2019,33(1):1262-1277. DOI: 10.1096/fj.201801059. [31] Gerami-NainiB, SmithA, MaioneAG, et al. Generation of induced pluripotent stem cells from diabetic foot ulcer fibroblasts using a nonintegrative Sendai virus[J]. Cell Reprogram, 2016,18(4):214-223. DOI: 10.1089/cell.2015.0087. [32] CassidyFC, ShortissC, MurphyCG, et al. Impact of type 2 diabetes mellitus on human bone marrow stromal cell number and phenotypic characteristics[J]. Int J Mol Sci, 2020,21(7):2476. DOI: 10.3390/ijms21072476. [33] NakayamaC, FujitaY, MatsumuraW, et al. The development of induced pluripotent stem cell-derived mesenchymal stem/stromal cells from normal human and RDEB epidermal keratinocytes[J]. J Dermatol Sci, 2018,91(3):301-310. DOI: 10.1016/j.jdermsci.2018.06.004. [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] TanRP, ChanAHP, LennartssonK, et al. Integration of induced pluripotent stem cell-derived endothelial cells with polycaprolactone/gelatin-based electrospun scaffolds for enhanced therapeutic angiogenesis[J]. Stem Cell Res Ther, 2018,9(1):70. DOI: 10.1186/s13287-018-0824-2. [36] 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[2022-04-06]. https://pubmed.ncbi.nlm.nih.gov/35291229/. DOI: 10.1093/burnst/tkac001. [37] YasudaS, KusakawaS, KurodaT, et al. Tumorigenicity-associated characteristics of human iPS cell lines[J]. PLoS One, 2018,13(10):e0205022. DOI: 10.1371/journal.pone.0205022. [38] QiaoY, AgboolaOS, HuX, et al. Tumorigenic and immunogenic properties of induced pluripotent stem cells: a promising cancer vaccine[J]. Stem Cell Rev Rep, 2020,16(6):1049-1061. DOI: 10.1007/s12015-020-10042-5. [39] DashBC, KorutlaL, VallabhajosyulaP, et al. Unlocking the potential of induced pluripotent stem cells for wound healing: the next frontier of regenerative medicine[J]. Adv Wound Care (New Rochelle), 2022,11(11):622-638. DOI: 10.1089/wound.2021.0049. [40] KobayashiH, EbisawaK, KambeM, et al. Effects of exosomes derived from the induced pluripotent stem cells on skin wound healing[J]. Nagoya J Med Sci, 2018,80(2):141-153. DOI: 10.18999/nagjms.80.2.141. [41] LeeMO, MoonSH, JeongHC, et al. Inhibition of pluripotent stem cell-derived teratoma formation by small molecules[J]. Proc Natl Acad Sci U S A, 2013,110(35):E3281-3290. DOI: 10.1073/pnas.1303669110. [42] Ben-DavidU, GanQF, Golan-LevT, et al. Selective elimination of human pluripotent stem cells by an oleate synthesis inhibitor discovered in a high-throughput screen[J]. Cell Stem Cell, 2013,12(2):167-179. DOI: 10.1016/j.stem.2012.11.015. [43] DossMX, SachinidisA. Current challenges of iPSC-based disease modeling and therapeutic implications[J]. Cells, 2019,8(5):403. DOI: 10.3390/cells8050403. [44] DeuseT, HuX, GravinaA, et al. Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients[J]. Nat Biotechnol, 2019,37(3):252-258. DOI: 10.1038/s41587-019-0016-3. [45] AzumaK, YamanakaS. Recent policies that support clinical application of induced pluripotent stem cell-based regenerative therapies[J]. Regenerative Therapy, 2016, 4:36-47. DOI: 10.1016/j.reth.2016.01.009. [46] MahmoodN, SuhTC, AliKM, et al. Induced pluripotent stem cell-derived corneal cells: current status and application[J/OL]. Stem Cell Rev Rep, 2022,(2022-08-01)[2022-08-31]. https://pubmed.ncbi.nlm.nih.gov/35913555/. DOI: 10.1007/s12015-022-10435-8. [published online ahead of print].
点击查看大图
计量
- 文章访问数: 228
- HTML全文浏览量: 31
- PDF下载量: 23
- 被引次数: 0