56 | 0 | 2 |
下载次数 | 被引频次 | 阅读次数 |
干细胞是一类在体内外特定环境下具有旺盛增殖和分化潜能的祖细胞,在组织损伤修复、再生医学、疾病治疗以及抗衰老等人类健康相关领域中,均具有巨大的应用价值;同时通过对干细胞的研究,可不断丰富人们对生命本质的认知。本文简要综述了有关干细胞从基础科研到实际应用领域国内外的研究历程,讨论了其与人类健康相关的发展趋势和未解的科学与技术问题,旨在为相关领域感兴趣以及欲拓展对生命本质认知的读者,提供有价值的参考资料和思考。
Abstract:Stem cells are a class of progenitor cells with vigorous proliferation and differentiation potential under specific conditions both in vivo and in vitro. They have significant application value in fields related to human health, such as tissue damage repair, regenerative medicine, disease treatment, and anti-aging. Meanwhile, through the study of stem cells, our understanding of the essence of life can be continuously enriched. This paper provides a brief overview of the research progress of stem cells from basic research to practical application fields and discusses the development trends and unsolved scientific and technical issues related to human health, aiming to provide valuable references and insights for readers interested in related field and those who wish to expand their understanding of the essence of life.
[ 1 ] Becker A J,Mc C E,Till J E.Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells [J].Nature,1963,197:452-454.
[ 2 ] Thomson J A,Itskovitz-Eldor J,Shapiro S S,et al.Embryonic stem cell lines derived from human blastocysts [J].Science,1998,282(5391):1145-1147.
[ 3 ] Richard A Y.Control of the embryonic stem cell state [J].Cell,2011,144:940-954.
[ 4 ] 前瞻产业研究院.中国干细胞医疗行业发展前景预测与投资战略规划分析报告[EB/OL].(2025-03-02)[2025-04-05].https://max.book118.com/html/2025/0301/7015051054010042.shtm.
[ 5 ] Sean J M,Allan C S.Stem cells and niches:mechanisms that promote stem cell maintenance throughout life [J].Cell,2008,132:598-611.
[ 6 ] Okuchi Y,Reeves J,Ng S S,et al.Wnt-modified materials mediate asymmetric stem cell division to direct human osteogenic tissue formation for bone repair[J].Nature Material,2021,20:108-118.
[ 7 ] Patricia A Zuk.The adipose-derived stem cell:looking back and looking ahead [J].Molecular Biology of the Cell,2010,21:1783-1787.
[ 8 ] Liguo Z,Suchart K,Yiyi Y,et al.Insulin negatively regulates dedifferentiation of mouse adipocytes in vitro [J].Adipocyte,2020,9 (1):24-34.
[ 9 ] Jie P,Suchart K,Laihao L,et al.Autophagy participants in the dedifferentiation of mouse 3T3-L1 adipocytes triggered by hypofunction of insulin signaling [J].Cellular Signalling,2021,80:109911.
[ 10 ] Stuart H O,Leonard I Z.Hematopoiesis:an evolving paradigm for stem cell biology [J].Cell,2008,132:631-644.
[ 11 ] Poliwoda S,Noor N,Downs E,et al.Stem cells:a comprehensive review of origins and emerging clinical roles in medical practice [J].Open Medical Publishing,2022,3(14):2035-8164.
[ 12 ] Wojciech Z,Maciej D,Maria S,et al.Stem cells:past,present,and future [J].Stem Cell Research & Therapy,2019,10:68.
[ 13 ] Guan J,Wang G,Wang J,et al.Chemical reprogramming of human somatic cells to pluripotent stem cells [J].Nature,2022,605:325-331.
[ 14 ] Hockemeyer D,Soldner F,Cook E G,et al.A drug-inducible system for direct reprogramming of human somatic cells to pluripotency [J].Cell Stem Cell,2008,3(3):346-353.
[ 15 ] Medet,Jumabay,Kristina,et al.Dedifferentiated fat cells:a cell source for regenerative medicine [J].World Journal of Stem Cells,2015,7 (10):1202-1214.
[ 16 ] Matsumoto T,Kano K,Kondo D,et al.Mature adipocyte-derived dedifferentiated fat cells exhibit multilineage potential [J].Journal of Cellular Physiology,2008,215(3):210-222.
[ 17 ] Smriti M.Do stem-cell transplants increase cancer risk?Long-lived recipients offer clues [J].Nature,2024:791.
[ 18 ] Masumi U O,Jacob H,Isaac J,et al.Characterization of clonal dynamics using duplex sequencing in donor-recipient pairs decades after hematopoietic cell transplantation [J].Science Translational Medicine,2024,16 (770).
[ 19 ] Hofer H R,Tuan R S.Secreted trophic factors of mesenchymal stem cells support neurovascular and musculoskeletal therapies [J].Stem Cell Research & Therapy,2016,7:131.
[ 20 ] Behzadifard M,Aboutaleb N,Dolatshahi M,et al.Neuroprotective effects of conditioned medium of mesenchymal stem cells (MSC-CM) as a therapy for ischemic stroke recovery:a systematic review [J].Neurochemical Research,2023,48,1280-1292.
[ 21 ] Smith A G.Embryo-derived stem cells:of mice and men [J].Annual Review of Cell and Developmental Biology,2001,17:435-462.
[ 22 ] Chen W,Huang Q,Ma S,Li M.Progress in dopaminergic cell replacement and regenerative strategies for Parkinson′s disease [J].ACS Chemical Neuroscience,2019,10(2):839-851.
[ 23 ] Madeleine J S,Madison C B P,Michael C F,et al.Neural stem cell treatment for perinatal brain injur:a systematic review and meta-analysis of preclinical studies [J].Stem Cells Translational Medicine,2021,10 (12):1621-1636.
[ 24 ] Rui W,Yiping G,Liying Z,et al.Physical exercise promotes integration of grafted cells and function recovery in an acute stroke rat model [J].Stem Cell Reports,2022,17(2):276-288.
[ 25 ] Titomanlio L,Kavelaars A,Dalous J,et al.Stem cell therapy for neonatal brain injury:perspectives and challenges [J].Annals of Neurology,2011,70 (5):698-712.
[ 26 ] Xu P F,Borges R M,Fillatre J,et al.Construction of a mammalian embryo model from stem cells organized by a morphogen signalling centre [J].Nature Communications,2021,12:3277.
[ 27 ] Jesse V V,Adriano B,Helene K,et al.Mouse embryonic stem cells self-organize into trunk-like structures with neural tube and somites[J].Science,2020,370(6522):eaba4937.
[ 28 ] Aguilera-Castrejon A,Oldak B,Shani T,et al.Exutero mouse embryogenesis from pre-gastrulation to late organogenesis [J].Nature,2021,593:119-124.
[ 29 ] Poliwoda S,Noor N,Downs E,et al.Stem cells:a comprehensive review of origins and emerging clinical roles in medical practice [J].Orthopedic Reviews,2022,3(14):
[ 30 ] Wojciech Z,Maciej D,Maria S,et al.Stem cells:past,present,and future [J].Stem Cell Research & Therapy,2019,10:68.
[ 31 ] Esparza A,Jimenez N,Borrego E A,et al.Review:Human stem cell-based 3D in vitro angiogenesis models for preclinical drug screening applications[J].Molecular Biology Reports,2024,51:260.
[ 32 ] Amadei G,Handford C,Qiu C,et al.Embryo model compeletes gastrulation to neurulation and organogenesis[J].Nature,22,610:143-153.
[ 33 ] Bailey A T W,Carlos W G,Riza M D,et al.Transgene directed induction of a stem cell-derived human embryo model [J].Nature,2023,06,15.545082.
[ 34 ] Bernardo O,Emilie W,Vladyslav B,et al.Transgene-free ex utero derivation of a human post-implantatione embryo model solely from genetically unmodified na ve PSCs [J].Nature,2023,06,14.544922.
[ 35 ] 华科同济干细胞联合湖北省再生医学研究院.2021中国(武汉)干细胞创新发展新技术新成果临床推广与应用高峰论坛[EB/OL].(2021-11-27)[2025-04-05].https://zhuanlan.zhihu.com/p/453016451.
[ 36 ] Bernadette A C,Connor J L,Mary J S,et al.Hematopoietic stem cells preferentially traffic misfolded proteins to aggresomes and depend on aggrephagy to maintain protein homeostasis [J].Cell Stem Cell,2023,30(4):460-472.
[ 37 ] Takebe T,Sekine K,Enomura M,et al.Vascularized and functional human liver from an iPSC-derived organ bud transplant [J].Nature,2013,499:481-484.
[ 38 ] Sekine K,Ogawa S,Tsuzuki S,et al.Generation of human induced pluripotent stem cell-derived liver buds with chemically defined and animal origin-free media [J].Scientific Reports,2020,10:17937.
[ 39 ] Koike H,Iwasawa K,Ouchi R,et al.Modelling human hepato-biliary-pancreatic organogenesis from the foregut-midgut boundary[J].Nature,2019,574(7776).
[ 40 ] Kasey Y C L,Hernan R,Carlos W G,et al.Mouse embryo model derived exclusively from embryonic stem cells undergoes neurulation and heart development[J].Cell Stem Cell,2022,29(10):1445-1458.
[ 41 ] Gianluca A,Charlotte E H,Chengxiang Q,et al.Synthetic embryos complete gastrulation to neurulation and organogenesis [J].Nature,2022,610,143-153.
[ 42 ] Rodriguez F A,Wolock S,Weinreb C,et al.Clonal analysis of lineage fate in native haematopoiesis [J].Nature,2018,553:212-216.
[ 43 ] Balboa D,Barsby T,Lithovius V,et al.Functional,metabolic and transcriptional maturation of human pancreatic islets derived from stem cells [J].Nature Biotechnology,2022,40:1042-1055.
[ 44 ] Chang H G,Dibyendu C,Cristiano P V,et al.Specific mesoderm subset derived from human pluripotent stem cells ameliorates microvascular pathology in type 2 diabetic mice [J].Science Advances,2022,8 (9).
[ 45 ] Murase Y,Yokogawa R,Yabuta Y,et al.In vitro reconstitution of epigenetic reprogramming in the human germ line [J].Nature,2024,631:170-178.
[ 46 ] Okubo T,Rivron N,Kabata M,et al.Hypoblast from human pluripotent stem cells regulates epiblast development [J].Nature,2024,626:357-366.
[ 47 ] Tan T,Wu J,Si C,et al.Chimeric contribution of human extended pluripotent stem cells to monkey embryos ex vivo [J].Cell,2021,184(8):2020-2032.
[ 48 ] Shi L ,Huang H ,Lu X ,et al.Effect of human umbilical cord-derived mesenchymal stem cells on lung damage in severe COVID-19 patients:a randomized,double-blind,placebo-controlled phase 2 trial [J].Signal Transduction and Targeted Therapy,2021,6(3):9.
[ 49 ] Guan J,Wang G,Wang J,et al.Chemical reprogramming of human somatic cells to pluripotent stem cells [J].Nature,2022,605:325-331.
[ 50 ] Mazid M.,Ward C,Luo Z,et al.Rolling back human pluripotent stem cells to an eight-cell embryo-like stage [J].Nature,2022,605:315-324.
[ 51 ] Li J,Zhu Q,Cao J,et al.Cynomolgus monkey embryo model captures gastrulation and early pregnency [J].Cell Stem Cell,2023,30(4):362-377.
[ 52 ] Liu W X,Tan S J,Wang Y F,et al.Melatonin promotes the proliferation of primordial germ cell-like cells derived from porcine skin-derived stem cells:a mechanistic analysis [J].Journal of Pineal Research,2022,73:e12833.
[ 53 ] Zhang S,Chen S,Li Y,et al.Melatonin as a promising agent of regulating stem cell biology and its application in disease therapy [J].Pharmacological Research,2017,117:252-260.
[ 54 ] 中国新闻网.全球首例人胚胎干细胞来源肝细胞治疗肝衰竭成功[EB/OL].(2022-08-25)[2025-03-19].https://www.chinanews.com.cn/sh/2022/08-25/9836847.shtml.
[ 55 ] Cheng H,Shang D,Zhou R.Germline stem cells in human [J].Signal Transduction and Targeted Therapy,2022,7:345.
[ 56 ] Gentile L,Cebria F,Bartscherer K.The planarian flatworm:anin vivomodel for stem cell biology and nervous system regeneration [J].Disease Models & Mechanisms,2011,4:12-19.
[ 57 ] Molina M D,Cebrià F.Decoding stem cells:an overview on planarian stem cell heterogeneity and lineage progression [J].Biomolecules,2021,11(10):1532.
[ 58 ] Martyn I,Kanno T Y,Ruzo A,et al.Self-organization of a human organizer by combined Wnt and Nodal signalling [J].Nature,2018,558:132-135.
[ 59 ] Chichagova V,Sanchez-Vera I,Armstrong L,et al.Generation of human induced pluripotent stem cells using RNA-based sendai virus system and pluripotency validation of the resulting cell population [J].Methods in Molecular Biology,New York:Humana Press,NY,2015:1353.
[ 60 ] Christa B,Hsu-Hsin C,Jose M P,et al.A murine ESC-like state facilitates transgenesis and homologous recombination in human pluripotent stem cells [J].Cell Stem Cell,2010,6:535-546.
[ 61 ] Chou Y F,Chen H H,Eijpe M,et al.The growth factor environment defines distinct pluripotent ground states in novel blastocyst-derived stem cells [J].Cell,2008,135:449-461.
[ 62 ] Charles E.Murry,Gordon Keller.Differentiation of embryonic stem cells to clinically relevant populations:lessons from embryonic development[J].Cell,2008,132:661-680.
[ 63 ] Takahashi K,Tanabe K,Ohnuki M,et al.Inducetion of pluripotent stem cells from adult human fibroblasts by defined factors [J].Cell,2007,131:861-872
[ 64 ] Lee J T.Epigenetic regulation by long noncoding RNAs [J].Science,2012,338(6113):1435-1439.
[ 65 ] Chen T,Dent S Y.Chromatin modifiers and romodellers:regulators of cellular differentiation [J].Nature Reviews Genetics,2014,15:93-106.
[ 66 ] Jonathan H,Pratibha S,Tiffany A T,et al.Rapid mobilization reveals a highly engraftable hematopoietic stem cell [J].Cell,2016,172(1):191-204.
[ 67 ] Elaine F,Tudorita T,Geraldine G.Socializing with the neighbors stem cells and their niche [J].Cell,2004,116:769-778.
[ 68 ] Takahashi K,Yamanaka S.Inducetion of pluripotent stem cells from mouse embryonic and adult fibrotblast celtures by defined factors [J].Cell,2006,126:663-676.
[ 69 ] Rudolf J,Richard Y.Stem cells,the molecular circuitry of pluripotency and nuclear reprogramming [J].Cell,2008,132:567-582.
[ 70 ] Pellegrini S,Piemonti L,Sordi V.Pluripotent stem cell replacement approaches to treat type 1 diabetes [J].Current Opinion in Pharmacology,2018,43:20-26.
[ 71 ] Tabar V,Sarva H,Lozano A M,et al.Phase I trial of hES cell-derived dopaminergic neurons for Parkinson′s disease [J].Nature,2025,641:978-983.
[ 72 ] Sawamoto N,Doi D,Nakanishi E,et al.Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson′s disease [J].Nature,2025,641:971-977.
[ 73 ] Gao C,Shi Q,Pan X,et al.Neuromuscular organoids model spinal neuromuscular pathologies in C9orf72 amyotrophic lateral sclerosis [J].Cell Reports,2024,43(3):113892.
[ 74 ] Bydon M.,Qu W,Moinuddin F M,et al.Intrathecal delivery of adipose-derived mesenchymal stem cells in traumatic spinal cord injury:phase I trial [J].Nature Communications,2024,15:2201
[ 75 ] Guo M,Pegoraro A F,Mao A,et al.Cell volume change through water efflux impacts cell stiffness and stem cell fate [J].Proceedings of the National Academy of Sciences of the United States of America,2017,114(41):201705179.
[ 76 ] Charles K F C,Gunsager S G,Rahul S,et al.Identification of the human skeletal stem cell [J].Cell,2018,175(1):43-56
[ 77 ] Xiao D,Liu X,Zhang M,et al.Direct reprogramming of fibroblasts into neural stem cells by single non-neural progenitor transcription factor Ptf1a [J].Nature Communications,2018,9:2865.
[ 78 ] Hu Y,Yang Y,Tan P,et al.Induction of mouse totipotent stem cells by a defined chemical cocktail [J].Nature,2023,617:792-797.
[ 79 ] Cote J A,Ostinelli G,Gauthier M F,et al.Focus on dedifferentiated adipocytes:characteristics,mechanisms,and possible applications [J].Cell Tissue Research,2019,378(3):385-398.
[ 80 ] Ono H,Oki Y,Bono H,et al.Gene expression profiling in multipotent DFAT cells derived from mature adipocytes [J].Biochemical and Biophysical Research Communications,2011,407(3):562-567.
[ 81 ] Jumabay M,Abdmaulen R,Ly A,et al.Pluripotent stem cells derived from mouse and human white mature adipocytes [J].Stem Cells Translational Medicine,2014,3(2):161-171.
[ 82 ] Murata D,Yamasaki A,Matsuzaki S,et al.Characteristics and multipotency of equine dedifferentiated fat cells [J].Journal of Equine Science,2016,27(2):57-65.
[ 83 ] Kwok K H,Lam K S,Xu A.Heterogeneity of white adipose tissue:molecular basis and clinical implications [J].Experimental & Molecular Medicine,2016,48(3).
[ 84 ] Louis F,Kitano S,Mano J F,et al.3D collagen microfibers stimulate the functionality of preadipocytes and maintain the phenotype of mature adipocytes for long term cultures [J].Acta Biomaterialia,2019,84:194-207.
[ 85 ] Tathiane M M,Artem S,Andrew J G,et al.Machine learning identifies stemness features associated with oncogenic dedifferentiation [J].Cell,2018,173:338-354.
[ 86 ] Chen Z,Han F,Du Y,et al.Hypoxic microenvironment in cancer:molecular mechanisms and therapeutic interventions [J].Signal Transduction and Targeted Therapy,2023 17,8(1):70.
[ 87 ] Bibhas R,Saradha V,Prasuna R,et al.Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors [J].Proceedings of the National Academy of Sciences of the United States of America,2018,115(21):E4741-E4750.
[ 88 ] Shoshani O,Zipori D.Mammalian cell dedifferentiation as a possible outcome of stress [J].Stem Cell Reviews Reports,2011,7(3):488-493.
[ 89 ] Liao Y,Zeng Z,Ly F,et al.In vivo dedifferentiation of adult adipose cells [J].PLoS One,2015,10(4).
[ 90 ] White M G,Shaw J A,Taylor R.Type 2 diabetes:the pathologic basis of reversible beta-cell dysfunction [J].Diabetes Care,2016,39(11):2080-2088.
[ 91 ] Kruglikov I L,Zhang Z,Scherer P E.The role of immature and mature adipocytes in hair cycling [J].Trends in Endocrinology and Metabolism,2019,30(2):93-105.
[ 92 ] Schffler A,Schlmerich J,Büchler C.Mechanisms of disease:adipocytokines and visceral adipose tissue-emerging role in intestinal and mesenteric diseases [J].Nature Reviews Gastroenterology & Hepatology,2005,2:103-111.
[ 93 ] Lei H,Hao H,Yihao Y,et al.Distinctive clinical and pathologic features of immature teratomas arising from induced pluripotent stem cell-derived beta cell injection in a diabetes patient [J].Stem Cells and Development,2022,31:5-6.
[ 94 ] Rohani L,Johnson A A,Naghsh P,et al.Concise review:molecular cytogenetics and quanlity control:clinical guanrdians for pluripotent stem cells [J].Stem Cells Translational Medicine,2018,7:867-875.
[ 95 ] 潘杰,中山皓博.人工智能及其在生命科学中的应用与展望[J].山东师范大学学报:自然科学版,2024,39(2):21-46.
[ 96 ] Robert F,Julia R,Aina B M,et al.Design principles of cell-state-specific enhancers in hematopoiesis [J].Cell,2025,188:1-17.
[ 97 ] Taskiran II,Spanier K,Dickmanken H,et al.Cell-type-directed design of synthetic enhancers [J].Nature,2024,626;212-220.
[ 98 ] Jianling Z,Xinxing Z,Huanjing H,et al.Generation of human expandable limb-bud-like progenitors via chemically induced dedifferentiation [J].Cell Stem Cell,2024,31(12);1732 - 1740.e6].
[ 99 ] Xi F,Shentong M,Alejandro B,et al.A foundation model of transcription across human cell types [J].Nature,2025,637(8047):965-973.
[100] Du Y,Liang Z,Wang S,et al.Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates [J].Nature Medicine,2022,28,272-282.
[101] Li X H,Guo D,Chen L Q,et al.Low-intensity ultrasound ameliorates brain organoid integration and rescues microcephaly deficits [J].Brain,2024,147:3817-3833.
[102] Xiaochun Y,Daichao C,Qiushi S,et al.A live-cell image-based machine learning strategy for reducing variability in PSC differentiation systems [J].Cell Discovery,2023,9 (1):53.
[103] Yan L,Tu W,Zaho X,et al.Stem cell transplantation extends the reproductive life span of naturally aging cynomolgus monkeys [J].Cell Discovery,2024,10:111.
[104] Pan H,Guan D,Liu X,et al.SIRT6 safeguards human mesenchymal stem cells from oxidative stress by coactivating NRF2 [J].Cell Research,2016,26:190-205.
[105] Rasouli M,Naeimzadeh Y,Haschemi N,et al.Age-related alterations in mesenchymal stem cell function:understanding mechanisms and seeking opportunities to bypass the cellular againg [J].Current Stem Cell Research & Therapy,2024,19(1):15-32.
[106] Hade M D,Suire C N,Suo Z.Mesenchymal stem cell-derived exosomes:applications in regenerative medicine [J].Cells,2021,10:1959.
[107] Zhu Y,Huang C,Zheng L,et al.Safety and efficacy of umbilical cord tissue-derived mesenchymal stem cells in the treatment of patients with aging frailty:a phase I/II randomized,double-blind,placebo-controlled study [J].Stem Cell Research & Therapy,2024,15:122.
[108] Han Y,Li X,Zhang Y.Mesenchymal stem cells for regenerative medicine [J].Cells,2019,8:886.
[109] Yan P,Li Q,Wang L,et al.FOXO3-engineered human ESC-derived vascular cells promote vascular protection and regeneration [J].Cell Stem Cell,2019,24(3):447-461.
[110] Todd W D,Samuel F,et al.A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring [J].Aging Cell,2024,24(1):e14351.https://doi.org/10.1111/acel.14351
[111] Lee L,James P,Zevon E S,et al.Optimism is associated with exceptional longevity in 2 epidemiologic cohorts of men and women [J].Proceedings of the National Academy of Sciences of the United States of America,2019,116:18357-18362.
[112] Hashimoto K,Kouno T,Ikawa T,et al.Single-cell transcriptomics reveals expansion of cytotoxic CD4 T cells in supercentenarians [J].Proceedings of the National Academy of Sciences of the United States of America,2019,116(48):24242-24251.
[113] 潘杰,刘来浩,牟建伟.肠道菌群与人类健康研究进展 [J].山东师范大学学报:自然科学版,2021,36(4):337-365.
[114] Wilmanski T M,Diener C,Rappaport N,et al.Gut microbiome pattern reflects healthy ageing and predicts survival in humans[J].Nature Metabolism,2021,3(2).
[115] Kikuch T,Morizane A,Doi D,et al.Human iPS cell-derived dopaminergic neurons function in a primate Parkinson′s disease model [J].Nature,2017,548:592-596.
[116] Wu C,Xu H H,Wu Z,et al.Subchondral injection of human umbilical cord mesenchymal stem cells ameliorates knee osteoarthritis by inhibiting osteoblast apoptosis and TGF-beta activity [J].Stem Cell Research & Therapy,2025,16:235.
基本信息:
DOI:
中图分类号:R329.2
引用信息:
[1]潘杰,中山皓博.干细胞与人类健康研究进展[J].山东师范大学学报(自然科学版),2025,40(02):97-122.
基金信息: