Application potential of induced pluripotent stem cells in the research and treatment of autoimmune diseases (Review)

Ren R, Jiang J, Li X and Zhang G: Research progress of autoimmune diseases based on induced pluripotent stem cells. Front Immunology. 15:13491382024. View Article : Google Scholar

Autoimmune Association, . Disease Information. Autoimmune Association; Clinton Township, MI: 2025, https://autoimmune.org/disease-information/May 18–2025

Conrad N, Misra S, Verbakel JY, Verbeke G, Molenberghs G, Taylor PN, Mason J, Sattar N, McMurray JJV, McInnes IB, et al: Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: A population-based cohort study of 22 million individuals in the UK. Lancet. 401:1878–1890. 2023. View Article : Google Scholar

Turtinen M, Härkönen T, Ilonen J, Parkkola A and Knip M; Finnish Pediatric Diabetes Register, : Seasonality in the manifestation of type 1 diabetes varies according to age at diagnosis in Finnish children. Acta Paediatr. 111:1061–1069. 2022. View Article : Google Scholar

Yamanaka S: Pluripotent stem cell-based cell therapy-promise and challenges. Cell Stem Cell. 27:523–531. 2020. View Article : Google Scholar

Shahjalal HM, Dayem AA, Lim KM, Jeon TI and Cho SG: Generation of pancreatic β cells for treatment of diabetes: Advances and challenges. Stem Cell Res Ther. 9:3552018. View Article : Google Scholar

Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS and Jones JM: Embryonic stem cell lines derived from human blastocysts. Science. 282:1145–1147. 1998. View Article : Google Scholar

Shen Z, Huang W, Liu J, Tian J, Wang S and Rui K: Effects of mesenchymal stem cell-derived exosomes on autoimmune diseases. Front Immunol. 12:7491922021. View Article : Google Scholar

Aldoghachi AF, Loh JK, Wang ML, Yang YP, Chien CS, Teh HX, Omar AH, Cheong SK, Yeap SK, Ho WY and Ong AHK: Current developments and therapeutic potentials of exosomes from induced pluripotent stem cells-derived mesenchymal stem cells. J Chin Med Assoc. 86:356–365. 2023. View Article : Google Scholar

Li W, Liu D, Zheng F, Zeng Z, Cai W, Luan S, Hong X, Tang D, Yin LH and Dai Y: Generation of systemic lupus erythematosus patient-derived induced pluripotent stem cells from blood. Stem Cells Dev. 30:227–233. 2021. View Article : Google Scholar

Joshi K, Cameron F, Tiwari S, Mannering SI, Elefanty AG and Stanley EG: Modeling type 1 diabetes using pluripotent stem cell technology. Front Endocrinol (Lausanne). 12:6356622021. View Article : Google Scholar

Holmqvist S, Lehtonen Š, Chumarina M, Puttonen KA, Azevedo C, Lebedeva O, Ruponen M, Oksanen M, Djelloul M, Collin A, et al: Creation of a library of induced pluripotent stem cells from Parkinsonian patients. NPJ Parkinsons Dis. 2:160092016. View Article : Google Scholar

Hollingsworth EW, Vaughn JE, Orack JC, Skinner C, Khouri J, Lizarraga SB, Hester ME, Watanabe F, Kosik KS and Imitola J: iPhemap: An atlas of phenotype to genotype relationships of human iPSC models of neurological diseases. EMBO Mol Med. 9:1742–1762. 2017. View Article : Google Scholar

Ullah I, Subbarao RB and Rho GJ: Human mesenchymal stem cells-current trends and future prospective. Biosci Rep. 35:e001912015. View Article : Google Scholar

Lee J, Kim Y, Yi H, Diecke S, Kim J, Jung H, Rim YA, Jung SM, Kim M, Kim YG, et al: Generation of disease-specific induced pluripotent stem cells from patients with rheumatoid arthritis and osteoarthritis. Arthritis Res Ther. 16:R412014. View Article : Google Scholar

Hew M, O'Connor K, Edel MJ and Lucas M: The possible future roles for iPSC-derived therapy for autoimmune diseases. J Clin Med. 4:1193–1206. 2015. View Article : Google Scholar

Natsumoto B, Shoda H, Fujio K, Otsu M and Yamamoto K: Investigation of the pathogenesis of autoimmune diseases by iPS cells. Nihon Rinsho Meneki Gakkai Kaishi. 40:48–53. 2017.(In Japanese). View Article : Google Scholar

Takahashi K and Yamanaka S: Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 126:663–676. 2006. View Article : Google Scholar

Kim K, Doi A, Wen B, Ng K, Zhao R, Cahan P, Kim J, Aryee MJ, Ji H, Ehrlich LI, et al: Epigenetic memory in induced pluripotent stem cells. Nature. 467:285–290. 2010. View Article : Google Scholar

Zhou T, Benda C, Dunzinger S, Huang Y, Ho JC, Yang J, Wang Y, Zhang Y, Zhuang Q, Li Y, et al: Generation of human induced pluripotent stem cells from urine samples. Nat Protoc. 7:2080–2089. 2012. View Article : Google Scholar

Zhang Y, McNeill E, Tian H, Soker S, Andersson KE, Yoo JJ and Atala A: Urine derived cells are a potential source for urological tissue reconstruction. J Urol. 180:2226–2233. 2008. View Article : Google Scholar

Bharadwaj S, Liu G, Shi Y, Markert C, Andersson KE, Atala A and Zhang Y: Characterization of urine-derived stem cells obtained from upper urinary tract for use in cell-based urological tissue engineering. Tissue Eng Part A. 17:2123–2132. 2011. View Article : Google Scholar

Xue Y, Cai X, Wang L, Liao B, Zhang H, Shan Y, Chen Q, Zhou T, Li X, Hou J, et al: Generating a non-integrating human induced pluripotent stem cell bank from urine-derived cells. PLoS One. 8:e705732013. View Article : Google Scholar

Jiang YF, Chen M, Zhang NN, Yang HJ, Rui Q and Zhou YF: In vitro and in vivo differentiation of induced pluripotent stem cells generated from urine-derived cells into cardiomyocytes. Biol Open. 7:bio0291572018.

Wang L, Wang L, Huang W, Su H, Xue Y, Su Z, Liao B, Wang H, Bao X, Qin D, et al: Generation of integration-free neural progenitor cells from cells in human urine. Nat Methods. 10:84–89. 2013. View Article : Google Scholar

Kim J, Koo BJ and Knoblich JA: Human organoids: Model systems for human biology and medicine. Nat Rev Mol Cell Biol. 21:571–584. 2020. View Article : Google Scholar

Lee G, Papapetrou EP, Kim H, Chambers SM, Tomishima MJ, Fasano CA, Ganat YM, Menon J, Shimizu F, Viale A, et al: Modelling pathogenesis and treatment of familial dysautonomia using patient-specific iPSCs. Nature. 461:402–406. 2009. View Article : Google Scholar

Israel MA, Yuan SH, Bardy C, Reyna SM, Mu Y, Herrera C, Hefferan MP, Van Gorp S, Nazor KL, Boscolo FS, et al: Probing sporadic and familial Alzheimer's disease using induced pluripotent stem cells. Nature. 482:216–220. 2012. View Article : Google Scholar

Kim C, Wong J, Wen J, Wang S, Wang C, Spiering S, Kan NG, Forcales S, Puri PL, Leone TC, et al: Studying arrhythmogenic right ventricular dysplasia with patient-specific iPSCs. Nature. 494:105–110. 2013. View Article : Google Scholar

Choi SM, Kim Y, Shim JS, Park JT, Wang RH, Leach SD, Liu JO, Deng C, Ye Z and Jang YY: Efficient drug screening and gene correction for treating liver disease using patient-specific stem cells. Hepatology. 57:2458–2468. 2013. View Article : Google Scholar

World Health Organization (WHO), . International Clinical Trials Registry Platform. WHO; Geneva: 2025, https://www.who.int/tools/clinical-trials-registry-platform?utm_source=chatgpt.comMay 20–2025

Armitage LH, Stimpson SE, Santostefano KE, Sui L, Ogundare S, Newby BN, Castro-Gutierrez R, Huber MK, Taylor JP, Sharma P, et al: Use of induced pluripotent stem cells to build isogenic systems and investigate type 1 diabetes. Front Endocrinol (Lausanne). 12:7372762021. View Article : Google Scholar

Laterza C, Merlini A, De Feo D, Ruffini F, Menon R, Onorati M, Fredrickx E, Muzio L, Lombardo A, Comi G, et al: iPSC-derived neural precursors exert a neuroprotective role in immune-mediated demyelination via the secretion of LIF. Nat Commun. 4:25972013. View Article : Google Scholar

Nakanishi A, Toyama S, Onozato D, Watanabe C, Hashita T, Iwao T and Matsunaga T: Effects of human induced pluripotent stem cell-derived intestinal organoids on colitis-model mice. Regen Ther. 21:351–361. 2022. View Article : Google Scholar

Haque M and Song J, Fino K, Sandhu P, Song X, Lei F, Zheng S, Ni B, Fang D and Song J: Stem cell-derived tissue-associated regulatory T cells ameliorate the development of autoimmunity. Sci Rep. 6:205882016. View Article : Google Scholar

Borgohain MP, Haridhasapavalan KK, Dey C, Adhikari P and Thummer RP: An insight into DNA-free Reprogramming approaches to generate integration-free induced pluripotent stem cells for prospective biomedical applications. Stem Cell Rev Rep. 15:286–313. 2019. View Article : Google Scholar

Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, et al: Induced pluripotent stem cell lines derived from human somatic cells. Science. 318:1917–1920. 2007. View Article : Google Scholar

Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K and Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell. 131:861–872. 2007. View Article : Google Scholar

Okita K, Ichisaka T and Yamanaka S: Generation of germline-competent induced pluripotent stem cells. Nature. 448:313–317. 2007. View Article : Google Scholar

Nakagawa M, Koyanagi M, Tanabe K, Takahashi K, Ichisaka T, Aoi T, Okita K, Mochiduki Y, Takizawa N and Yamanaka S: Generation of induced pluripotent stem cells without Myc from mouse and human fibroblasts. Nat Biotechnol. 26:101–106. 2008. View Article : Google Scholar

Okita K, Matsumura Y, Sato Y, Okada A, Morizane A, Okamoto S, Hong H, Nakagawa M, Tanabe K, Tezuka KI, et al: A more efficient method to generate integration-free human iPS cells. Nat Methods. 8:409–412. 2011. View Article : Google Scholar

Karagonlar ZF, Akbari S, Karabicici M, Sahin E, Avci ST, Ersoy N, Ates KE, Balli T, Karacicek B, Kaplan K, et al: A novel function for KLF4 in modulating the de-differentiation of EpCAM⁻/CD133⁻ nonStem cells into EpCAM⁺/CD133⁺ liver cancer stem cells in HCC cell line HuH7. Cells. 9:11982020. View Article : Google Scholar

Kumar SM, Liu S, Lu H, Zhang H, Zhang PJ, Gimotty PA, Guerra M, Guo W and Xu X: Acquired cancer stem cell phenotypes through Oct4-mediated dedifferentiation. Oncogene. 31:4898–4911. 2012. View Article : Google Scholar

Stadtfeld M, Nagaya M, Utikal J, Weir G and Hochedlinger K: Induced pluripotent stem cells generated without viral integration. Science. 322:945–949. 2008. View Article : Google Scholar

Yu J, Hu K, Smuga-Otto K, Tian S, Stewart R, Slukvin II and Thomson JA: Human induced pluripotent stem cells free of vector and transgene sequences. Science. 324:797–801. 2009. View Article : Google Scholar

Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, Takada N, Inoue M, Hasegawa M, Kawamata S and Nishikawa S: Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proc Natl Acad Sci USA. 108:14234–14239. 2011. View Article : Google Scholar

Desponts C and Ding S: Using small molecules to improve generation of induced pluripotent stem cells from somatic cells. Methods Mol Biol. 636:207–218. 2010. View Article : Google Scholar

Kaji K, Norrby K, Paca A, Mileikovsky M, Mohseni P and Woltjen K: Virus-free induction of pluripotency and subsequent excision of reprogramming factors. Nature. 458:771–775. 2009. View Article : Google Scholar

Okita K, Nakagawa M, Hyenjong H, Ichisaka T and Yamanaka S: Generation of mouse induced pluripotent stem cells without viral vectors. Science. 322:949–953. 2008. View Article : Google Scholar

Chou BK, Mali P, Huang X, Ye Z, Dowey SN, Resar LM, Zou C, Zhang YA, Tong J and Cheng L: Efficient human iPS cell derivation by a non-integrating plasmid from blood cells with unique epigenetic and gene expression signatures. Cell Res. 21:518–529. 2011. View Article : Google Scholar

Kouskoff V, Korganow AS, Duchatelle V, Degott C, Benoist C and Mathis D: Organ-specific disease provoked by systemic autoimmunity. Cell. 87:811–822. 1996. View Article : Google Scholar

Thomas OG, Haigh TA, Croom-Carter D, Leese A, Van Wijck Y, Douglas MR, Rickinson A, Brooks JM and Taylor GS: Heightened Epstein-Barr virus immunity and potential cross-reactivities in multiple sclerosis. PLoS Pathog. 20:e10121772024. View Article : Google Scholar

Owen TJ, O'Neil JD, Dawson CW, Hu C, Chen X, Yao Y, Wood VH, Mitchell LE, White RJ, Young LS and Arrand JR: Epstein-Barr virus-encoded EBNA1 enhances RNA polymerase III-dependent EBER expression through induction of EBER-associated cellular transcription factors. Mol Cancer. 9:2412010. View Article : Google Scholar

Malchenko S, Xie J, de Fatima Bonaldo M, Vanin EF, Bhattacharyya BJ, Belmadani A, Xi G, Galat V, Goossens W, Seftor RE, et al: Onset of rosette formation during spontaneous neural differentiation of hESC and hiPSC colonies. Gene. 534:400–407. 2014. View Article : Google Scholar

Sougawa N, Miyagawa S, Fukushima S, Kawamura A, Yokoyama J, Ito E, Harada A, Okimoto K, Mochizuki-Oda N, Saito A and Sawa Y: Immunologic targeting of CD30 eliminates tumourigenic human pluripotent stem cells, allowing safer clinical application of hiPSC-based cell therapy. Sci Rep. 8:37262018. View Article : Google Scholar

Hayashi R, Ishikawa Y, Katori R, Sasamoto Y, Taniwaki Y, Takayanagi H, Tsujikawa M, Sekiguchi K, Quantock AJ and Nishida K: Coordinated generation of multiple ocular-like cell lineages and fabrication of functional corneal epithelial cell sheets from human iPS cells. Nat Protoc. 12:683–696. 2017. View Article : Google Scholar

Hayashi R, Ishikawa Y, Katayama T, Quantock AJ and Nishida K: CD200 facilitates the isolation of corneal epithelial cells derived from human pluripotent stem cells. Sci Rep. 8:165502018. View Article : Google Scholar

Laurent LC, Ulitsky I, Slavin I, Tran H, Schork A, Morey R, Lynch C, Harness JV, Lee S, Barrero MJ, et al: Dynamic changes in the copy number of pluripotency and cell proliferation genes in human ESCs and iPSCs during reprogramming and time in culture. Cell Stem Cell. 8:106–118. 2011. View Article : Google Scholar

Hussein SM, Batada NN, Vuoristo S, Ching RW, Autio R, Närvä E, Ng S, Sourour M, Hämäläinen R, Olsson C, et al: Copy number variation and selection during reprogramming to pluripotency. Nature. 471:58–62. 2011. View Article : Google Scholar

Rouhani FJ, Nik-Zainal S, Wuster A, Li Y, Conte N, Koike-Yusa H, Kumasaka N, Vallier L, Yusa K and Bradley A: Mutational history of a human cell lineage from somatic to induced pluripotent stem cells. PLoS Genet. 12:e10059322016. View Article : Google Scholar

Merkle FT, Ghosh S, Kamitaki N, Mitchell J, Avior Y, Mello C, Kashin S, Mekhoubad S, Ilic D, Charlton M, et al: Human pluripotent stem cells recurrently acquire and expand dominant negative P53 mutations. Nature. 545:229–233. 2017. View Article : Google Scholar

Mueller DL: Mechanisms maintaining peripheral tolerance. Nat Immunol. 11:21–27. 2010. View Article : Google Scholar

Takaba H and Takayanagi H: The mechanisms of T cell selection in the thymus. Trends Immunol. 38:805–816. 2017. View Article : Google Scholar

Givony T, Leshkowitz D, Del Castillo D, Nevo S, Kadouri N, Dassa B, Gruper Y, Khalaila R, Ben-Nun O, Gome T, et al: Thymic mimetic cells function beyond self-tolerance. Nature. 622:164–172. 2023. View Article : Google Scholar

Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PI, Le JM, Lee HS, Batliwalla F, et al: STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med. 357:977–986. 2007. View Article : Google Scholar

Festenstein H, Awad J, Hitman GA, Cutbush S, Groves AV, Cassell P, Ollier W and Sachs JA: New HLA DNA polymorphisms associated with autoimmune diseases. Nature. 322:64–67. 1986. View Article : Google Scholar

Gregersen PK: Gaining insight into PTPN22 and autoimmunity. Nat Genet. 37:1300–1302. 2005. View Article : Google Scholar

Edner NM, Carlesso G, Rush JS and Walker LSK: Targeting co-stimulatory molecules in autoimmune disease. Nat Rev Drug Discov. 19:860–883. 2020. View Article : Google Scholar

Maier LM, Lowe CE, Cooper J, Downes K, Anderson DE, Severson C, Clark PM, Healy B, Walker N, Aubin C, et al: IL2RA genetic heterogeneity in multiple sclerosis and type 1 diabetes susceptibility and soluble interleukin-2 receptor production. PLoS Genet. 5:e10003222009. View Article : Google Scholar

Soldan SS and Lieberman PM: Epstein-Barr virus and multiple sclerosis. Nat Rev Microbiol. 21:51–64. 2023. View Article : Google Scholar

Houen G and Trier NH: Epstein-Barr virus and systemic autoimmune diseases. Front Immunol. 11:5873802020. View Article : Google Scholar

Jog NR and James JA: Epstein barr virus and autoimmune responses in systemic lupus erythematosus. Front Immunol. 11:6239442020. View Article : Google Scholar

Nagata S, Hanayama R and Kawane K: Autoimmunity and the clearance of dead cells. Cell. 140:619–630. 2010. View Article : Google Scholar

Kim HJ and Cantor H: Regulatory T cells subdue an autoimmune disease. Nature. 572:443–445. 2019. View Article : Google Scholar

Jayaprakash B, Savira M, Mahmood AAR and Prasanna M: The role of stem cell therapies in the treatment of neurodegenerative diseases. Curr Stem Cell Res Ther. 20:146–165. 2025. View Article : Google Scholar

Reich DS, Lucchinetti CF and Calabresi PA: Multiple sclerosis. N Engl J Med. 378:169–180. 2018. View Article : Google Scholar

Dedoni S, Scherma M, Camoglio C, Siddi C, Dazzi L, Puliga R, Frau J, Cocco E and Fadda P: An overall view of the most common experimental models for multiple sclerosis. Neurobiol Dis. 184:1062302023. View Article : Google Scholar

Scolding N: Adult stem cells and multiple sclerosis. Cell Prolif. 44:35–38. 2011. View Article : Google Scholar

Christodoulou MV, Petkou E, Atzemoglou N, Gkorla E, Karamitrou A, Simos YV, Bellos S, Bekiari C, Kouklis P, Konitsiotis S, et al: Cell replacement therapy with stem cells in multiple sclerosis, a systematic review. Human Cell. 37:9–53. 2024. View Article : Google Scholar

Tahmasebi F, Asl ER, Vahidinia Z and Barati S: Stem cell-derived exosomal MicroRNAs as novel potential approach for multiple sclerosis treatment. Cell Mol Neurobiol. 44:442024. View Article : Google Scholar

Mohseni SO, Au KM, Issa W, Ruan L, Stuve O and Wang AZ: Multiple sclerosis treatments a review of current biomedical engineering approaches. Biomaterials. 313:1228072025. View Article : Google Scholar

Dadfar S, Yazdanpanah E, Pazoki A, Nemati MH, Eslami M, Haghmorad D and Oksenych V: The role of mesenchymal stem cells in modulating adaptive immune responses in multiple sclerosis. Cells. 13:15562024. View Article : Google Scholar

Zhang Q, Chen Z, Zhang K, Zhu J and Jin T: FGF/FGFR system in the central nervous system demyelinating disease: Recent progress and implications for multiple sclerosis. CNS Neurosci Ther. 29:1497–1511. 2023. View Article : Google Scholar

Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, La Rocca N, Uitdehaag B, van der Mei I, et al: Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Mult Scler. 26:1816–1821. 2020. View Article : Google Scholar

McGinley MP, Goldschmidt CH and Rae-Grant AD: Diagnosis and treatment of multiple sclerosis: A review. JAMA. 325:765–779. 2021. View Article : Google Scholar

Rio J, Comabella M and Montalban X: Multiple sclerosis: Current treatment algorithms. Curr Opin Neurol. 24:230–237. 2011. View Article : Google Scholar

Daniels K, van der Nat PB, Frequin STFM, van der Wees PJ, Biesma DH, Hoogervorst ELJ and van de Garde EMW: Real-World results of ocrelizumab treatment for primary progressive multiple sclerosis. Mult Scler Int. 2020:54634512020.

Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, de Bakker PI, Gabriel SB, Mirel DB, Ivinson AJ, et al: Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 357:851–862. 2007. View Article : Google Scholar

Sawcer S, Hellenthal G, Pirinen M, Spencer CC, Patsopoulos NA, Moutsianas L, Dilthey A, Su Z, Freeman C, Hunt SE, et al: Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis. Nature. 476:214–219. 2011. View Article : Google Scholar

Owens T and Sriram S: The immunology of multiple sclerosis and its animal model, experimental allergic encephalomyelitis. Neurol Clin. 13:51–73. 1995. View Article : Google Scholar

Komiyama Y, Nakae S, Matsuki T, Nambu A, Ishigame H, Kakuta S, Sudo K and Iwakura Y: IL-17 plays an important role in the development of experimental autoimmune encephalomyelitis. J Immunol. 177:566–573. 2006. View Article : Google Scholar

Fletcher JM, Lalor SJ, Sweeney CM, Tubridy N and Mills KH: T cells in multiple sclerosis and experimental autoimmune encephalomyelitis. Clin Exp Immunol. 162:1–11. 2010. View Article : Google Scholar

Stys PK, Zamponi GW, van Minnen J and Geurts JJ: Will the real multiple sclerosis please stand up? Nat Rev Neurosci. 13:507–514. 2012. View Article : Google Scholar

Fagiani F, Pedrini E, Taverna S, Brambilla E, Murtaj V, Podini P, Ruffini F, Butti E, Braccia C, Andolfo A, et al: A glia-enriched stem cell 3D model of the human brain mimics the glial-immune neurodegenerative phenotypes of multiple sclerosis. Cell Rep Med. 5:1016802024. View Article : Google Scholar

Nishihara H, Perriot S, Gastfriend BD, Steinfort M, Cibien C, Soldati S, Matsuo K, Guimbal S, Mathias A, Palecek SP, et al: Intrinsic blood-brain barrier dysfunction contributes to multiple sclerosis pathogenesis. Brain. 145:4334–4348. 2022. View Article : Google Scholar

Mutukula N, Man Z, Takahashi Y, Martinez FI, Morales M, Carreon-Guarnizo E, Clares RH, Garcia-Bernal D, Martinez LM, Lajara J, et al: Generation of RRMS and PPMS specific iPSCs as a platform for modeling Multiple Sclerosis. Stem Cell Res. 53:1023192021. View Article : Google Scholar

Tiane A, Schepers M, Reijnders RA, van Veggel L, Chenine S, Rombaut B, Dempster E, Verfaillie C, Wasner K, Grünewald A, et al: From methylation to myelination: Epigenomic and transcriptomic profiling of chronic inactive demyelinated multiple sclerosis lesions. Acta Neuropathol. 146:283–299. 2023. View Article : Google Scholar

Thiruvalluvan A, Czepiel M, Kap YA, Mantingh-Otter I, Vainchtein I, Kuipers J, Bijlard M, Baron W, Giepmans B, Brück W, et al: Survival and functionality of human induced pluripotent stem cell-derived oligodendrocytes in a nonhuman primate model for multiple sclerosis. Stem Cells Transl Med. 5:1550–1561. 2016. View Article : Google Scholar

Li P, Li M, Tang X, Wang S, Zhang YA and Chen Z: Accelerated generation of oligodendrocyte progenitor cells from human induced pluripotent stem cells by forced expression of Sox10 and Olig2. Sci China Life Sci. 59:1131–1138. 2016. View Article : Google Scholar

Yang N, Zuchero JB, Ahlenius H, Marro S, Ng YH, Vierbuchen T, Hawkins JS, Geissler R, Barres BA and Wernig M: Generation of oligodendroglial cells by direct lineage conversion. Nat Biotechnol. 31:434–439. 2013. View Article : Google Scholar

Najm FJ, Lager AM, Zaremba A, Wyatt K, Caprariello AV, Factor DC, Karl RT, Maeda T, Miller RH and Tesar PJ: Transcription factor-mediated reprogramming of fibroblasts to expandable, myelinogenic oligodendrocyte progenitor cells. Nat Biotechnol. 31:426–433. 2013. View Article : Google Scholar

Pluchino S, Smith JA and Peruzzotti-Jametti L: Promises and limitations of neural stem cell therapies for progressive multiple sclerosis. Trends Mol Med. 26:898–912. 2020. View Article : Google Scholar

Ottoboni L, von Wunster B and Martino G: Therapeutic plasticity of neural stem cells. Front Neurol. 11:1482020. View Article : Google Scholar

Yazdi A, Khanghahi AM, Baharvand H and Javan M: Fingolimod enhances oligodendrocyte differentiation of transplanted human induced pluripotent stem cell-derived neural progenitors. Iran J Pharm Res. 17:1444–1457. 2018.

Windrem MS, Schanz SJ, Zou L, Chandler-Militello D, Kuypers NJ, Nedergaard M, Lu Y, Mariani JN and Goldman SA: Human glial progenitor cells effectively remyelinate the demyelinated adult brain. Cell Rep. 31:1076582020. View Article : Google Scholar

Safiri S, Kolahi AA, Hoy D, Smith E, Bettampadi D, Mansournia MA, Almasi-Hashiani A, Ashrafi-Asgarabad A, Moradi-Lakeh M, Qorbani M, et al: Global, regional and national burden of rheumatoid arthritis 1990–2017: A systematic analysis of the Global Burden of Disease study 2017. Ann Rheum Dis. 78:1463–1471. 2019. View Article : Google Scholar

Kim H and Sung YK: Epidemiology of rheumatoid arthritis in Korea. J Rheum Dis. 28:60–67. 2021. View Article : Google Scholar

Bernardy C, Dalecky M, Guillaud-Rollin S, Dujardin T, Gastaldi R and Baillet A: Severity and mortality of inflammatory rheumatic diseases: Evolution of approaches. Joint Bone Spine. 92:1059312025. View Article : Google Scholar

Lau CS: Burden of rheumatoid arthritis and forecasted prevalence to 2050. Lancet Rheumatol. 5:e567–e568. 2023. View Article : Google Scholar

Liu H, Zhu Y, Gao Y, Qi D, Zhao L, Zhao L, Liu C, Tao T, Zhou C, Sun X, et al: NR1D1 modulates synovial inflammation and bone destruction in rheumatoid arthritis. Cell Death Dis. 11:1292020. View Article : Google Scholar

Chen S, Guo C, Wang R, Feng Z, Liu Z, Wu L, Zhao D, Zheng S, Chen F, Zhang D, et al: Monocytic MDSCs skew Th17 cells toward a pro-osteoclastogenic phenotype and potentiate bone erosion in rheumatoid arthritis. Rheumatology (Oxford). 60:2409–2420. 2021. View Article : Google Scholar

Komatsu N and Takayanagi H: Mechanisms of joint destruction in rheumatoid arthritis-immune cell-fibroblast-bone interactions. Nat Rev Rheumatol. 18:415–429. 2022. View Article : Google Scholar

Kumar LD, Karthik R, Gayathri N and Sivasudha T: Advancement in contemporary diagnostic and therapeutic approaches for rheumatoid arthritis. Biomed Pharmacother. 79:52–61. 2016. View Article : Google Scholar

Rim YA, Park N, Nam Y and Ju JH: Generation of induced-pluripotent stem cells using fibroblast-like synoviocytes isolated from joints of rheumatoid arthritis patients. J Vis Exp. 16:540722016.

Wolnik J, Kubiak G, Skoczyńska M, Wiland P, Fearon U, Veale D, Dulak J and Biniecka M: Generation of two hiPSC lines, (DMBi003-A and DMBi004-A), by reprogramming peripheral blood mononuclear cells and fibroblast-like synoviocytes from rheumatoid arthritis patients. Stem Cell Res. 64:1028862022. View Article : Google Scholar

Lee J, Jung SM, Ebert AD, Wu H, Diecke S, Kim Y, Yi H, Park SH and Ju JH: Generation of functional cardiomyocytes from the synoviocytes of patients with rheumatoid arthritis via induced pluripotent stem cells. Sci Rep. 6:326692016. View Article : Google Scholar

Kim J, Kang SC, Yoon NE, Kim Y, Choi J, Park N, Jung H, Jung BH and Ju JH: Metabolomic profiles of induced pluripotent stem cells derived from patients with rheumatoid arthritis and osteoarthritis. Stem Cell Res Ther. 10:3192019. View Article : Google Scholar

Collins KH, Pferdehirt L, Saleh LS, Savadipour A, Springer LE, Lenz KL, Thompson DM Jr, Oswald SJ, Pham CTN and Guilak F: Hydrogel encapsulation of genome-engineered stem cells for long-term self-regulating anti-cytokine therapy. Gels. 9:1692023. View Article : Google Scholar

Eremeev A, Pikina A, Ruchko Y and Bogomazova A: Clinical potential of cellular material sources in the generation of iPSC-based products for the regeneration of articular cartilage. Int J Mol Sci. 24:144082023. View Article : Google Scholar

Nakamura A, Murata D, Fujimoto R, Tamaki S, Nagata S, Ikeya M, Toguchida J and Nakayama K: Bio-3D printing iPSC-derived human chondrocytes for articular cartilage regeneration. Biofabrication. 13:10.1088/1758–5090/ac1c99. 2021. View Article : Google Scholar

Barber MRW, Drenkard C, Falasinnu T, Hoi A, Mak A, Kow NY, Svenungsson E, Peterson J, Clarke AE and Ramsey-Goldman R: Global epidemiology of systemic lupus erythematosus. Nat Rev Rheumatol. 17:515–532. 2021. View Article : Google Scholar

Hanna N, Silverberg OM, Reaume M, Gladman D, Davis MDP, Piguet V and Alavi A: Incidence, prevalence, and predictors of inflammatory arthritis in patients with hidradenitis suppurativa: A systematic review and meta-analysis. Int J Dermatol. 61:1069–1079. 2022. View Article : Google Scholar

Kiriakidou M and Ching CL: Systemic lupus erythematosus. Ann Intern Med. 172:ITC81–ITC96. 2020. View Article : Google Scholar

Fenton K: The effect of cell death in the initiation of lupus nephritis. Clin Exp Immunol. 179:11–16. 2015. View Article : Google Scholar

Munoz LE, Lauber K, Schiller M, Manfredi AA and Herrmann M: The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol. 6:280–289. 2010. View Article : Google Scholar

Kato H and Fujita T: RIG-I-like receptors and autoimmune diseases. Curr Opin Immunol. 37:40–45. 2015. View Article : Google Scholar

Thanou A, Jupe E, Purushothaman M, Niewold TB and Munroe ME: Clinical disease activity and flare in SLE: Current concepts and novel biomarkers. J Autoimmun. 119:1026152021. View Article : Google Scholar

Vrinceanu D, Dumitru M, Banica B, Eftime IS, Patrascu O, Costache A, Cherecheanu MP and Georgescu MG: Role of temporal artery resection in Horton's arteritis (Review). Exp Ther Med. 22:10992021. View Article : Google Scholar

Xiong W and Lahita RG: Pragmatic approaches to therapy for systemic lupus erythematosus. Nat Rev Rheumatol. 10:97–107. 2014. View Article : Google Scholar

Park N, Rim YA, Jung H, Nam Y and Ju JH: Lupus heart disease modeling with combination of induced pluripotent stem cell-derived cardiomyocytes and lupus patient serum. Int J Stem Cells. 15:233–246. 2022. View Article : Google Scholar

Shoda H, Natsumoto B and Fujio K: Investigation of immune-related diseases using patient-derived induced pluripotent stem cells. Inflamm Regen. 43:512023. View Article : Google Scholar

Chen Y, Luo R, Xu Y, Cai X, Li W, Tan K, Huang J and Dai Y: Generation of systemic lupus erythematosus-specific induced pluripotent stem cells from urine. Rheumatol Int. 33:2127–2134. 2013. View Article : Google Scholar

Son MY, Lee MO, Jeon H, Seol B, Kim JH, Chang JS and Cho YS: Generation and characterization of integration-free induced pluripotent stem cells from patients with autoimmune disease. Exp Mol Med. 48:e2322016. View Article : Google Scholar

Tang D, Chen Y, He H, Huang J, Chen W, Peng W, Lu Q and Dai Y: Integrated analysis of mRNA, microRNA and protein in systemic lupus erythematosus-specific induced pluripotent stem cells from urine. BMC Genomics. 17:4882016. View Article : Google Scholar

Guillet S, Lazarov T, Jordan N, Boisson B, Tello M, Craddock B, Zhou T, Nishi C, Bareja R, Yang H, et al: ACK1 and BRK non-receptor tyrosine kinase deficiencies are associated with familial systemic lupus and involved in efferocytosis. Elife. 13:RP960852024. View Article : Google Scholar

Natsumoto B, Shoda H, Nagafuchi Y, Ota M, Okumura T, Horie Y, Okamura T, Yamamoto K, Tsuji M, Otsu M, et al: Functional evaluation of rare OASL variants by analysis of SLE patient-derived iPSCs. J Autoimmun. 139:1030852023. View Article : Google Scholar

Ota M, Nagafuchi Y, Hatano H, Ishigaki K, Terao C, Takeshima Y, Yanaoka H, Kobayashi S, Okubo M, Shirai H, et al: Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases. Cell. 184:3006–3021.e17. 2021. View Article : Google Scholar

De Angelis MT, Santamaria G, Parrotta EI, Scalise S, Lo Conte M, Gasparini S, Ferlazzo E, Aguglia U, Ciampi C, Sgura A and Cuda G: Establishment and characterization of induced pluripotent stem cells (iPSCs) from central nervous system lupus erythematosus. J Cell Mol Med. 23:7382–7394. 2019. View Article : Google Scholar

Graham KL, Sutherland RM, Mannering SI, Zhao Y, Chee J, Krishnamurthy B, Thomas HE, Lew AM and Kay TW: Pathogenic mechanisms in type 1 diabetes: the islet is both target and driver of disease. Rev Diabet Stud. 9:148–168. 2012. View Article : Google Scholar

Seaquist ER, Anderson J, Childs B, Cryer P, Dagogo-Jack S, Fish L, Heller SR, Rodriguez H, Rosenzweig J and Vigersky R; American Diabetes Association; Endocrine Society, : Hypoglycemia and diabetes: A report of a workgroup of the American Diabetes Association and the Endocrine Society. Diabetes Care. 36:1384–1395. 2013. View Article : Google Scholar

Chiang JL, Kirkman MS, Laffel LM and Peters AL; Type 1 Diabetes Sourcebook Authors, : Type 1 diabetes through the life span: A position statement of the American Diabetes Association. Diabetes Care. 37:2034–2054. 2014. View Article : Google Scholar

Gregory GA, Robinson TIG, Linklater SE, Wang F, Colagiuri S, de Beaufort C, Donaghue KC; International Diabetes Federation Diabetes Atlas Type 1 Diabetes in Adults Special Interest Group, ; Magliano DJ, Maniam J, et al: Global incidence, prevalence, and mortality of type 1 diabetes in 2021 with projection to 2040: A modelling study. Lancet Diabetes Endocrinol. 10:741–760. 2022. View Article : Google Scholar

Lacy PE and Kostianovsky M: Method for the isolation of intact islets of Langerhans from the rat pancreas. Diabetes. 16:35–39. 1967. View Article : Google Scholar

Hering BJ, Clarke WR, Bridges ND, Eggerman TL, Alejandro R, Bellin MD, Chaloner K, Czarniecki CW, Goldstein JS, Hunsicker LG, et al: Phase 3 trial of transplantation of human islets in type 1 diabetes complicated by severe hypoglycemia. Diabetes Care. 39:1230–1240. 2016. View Article : Google Scholar

Bennet W, Sundberg B, Lundgren T, Tibell A, Groth CG, Richards A, White DJ, Elgue G, Larsson R, Nilsson B and Korsgren O: Damage to porcine islets of Langerhans after exposure to human blood in vitro, or after intraportal transplantation to cynomologus monkeys: protective effects of sCR1 and heparin. Transplantation. 69:711–719. 2000. View Article : Google Scholar

Korbutt GS, Elliott JF, Ao Z, Smith DK, Warnock GL and Rajotte RV: Large scale isolation, growth, and function of porcine neonatal islet cells. J Clin Invest. 97:2119–2129. 1996. View Article : Google Scholar

van der Windt DJ, Bottino R, Kumar G, Wijkstrom M, Hara H, Ezzelarab M, Ekser B, Phelps C, Murase N, Casu A, et al: Clinical islet xenotransplantation: How close are we? Diabetes. 61:3046–3055. 2012. View Article : Google Scholar

Naqvi RA, Naqvi AR, Singh A, Priyadarshini M, Balamurugan AN and Layden BT: The future treatment for type 1 diabetes: Pig islet- or stem cell-derived β cells? Front Endocrinol (Lausanne). 13:10010412022. View Article : Google Scholar

Pagliuca FW, Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D and Melton DA: Generation of functional human pancreatic beta cells in vitro. Cell. 159:428–439. 2014. View Article : Google Scholar

Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O'Dwyer S, Quiskamp N, Mojibian M, Albrecht T, et al: Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 32:1121–1133. 2014. View Article : Google Scholar

Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, et al: Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nat Med. 22:306–311. 2016. View Article : Google Scholar

Leite NC, Sintov E, Meissner TB, Brehm MA, Greiner DL, Harlan DM and Melton DA: modeling type 1 diabetes in vitro using human pluripotent stem cells. Cell Rep. 32:1078942020. View Article : Google Scholar

Cai EP, Ishikawa Y, Zhang W, Leite NC, Li J, Hou S, Kiaf B, Hollister-Lock J, Yilmaz NK, Schiffer CA, et al: Genome-scale in vivo CRISPR screen identifies RNLS as a target for beta cell protection in type 1 diabetes. Nat Metab. 2:934–945. 2020. View Article : Google Scholar

Hosokawa Y, Hanafusa T and Imagawa A: Pathogenesis of fulminant type 1 diabetes: Genes, viruses and the immune mechanism, and usefulness of patient-derived induced pluripotent stem cells for future research. J Diabetes Investig. 10:1158–1164. 2019. View Article : Google Scholar

El Khatib MM, Ohmine S, Jacobus EJ, Tonne JM, Morsy SG, Holditch SJ, Schreiber CA, Uetsuka K, Fusaki N, Wigle DA, et al: Tumor-free transplantation of patient-derived induced pluripotent stem cell progeny for customized islet regeneration. Stem Cells Transl Med. 5:694–702. 2016. View Article : Google Scholar

Haller C, Piccand J, De Franceschi F, Ohi Y, Bhoumik A, Boss C, De Marchi U, Jacot G, Metairon S, Descombes P, et al: Macroencapsulated human iPSC-derived pancreatic progenitors protect against STZ-induced hyperglycemia in mice. Stem Cell Reports. 12:787–800. 2019. View Article : Google Scholar

Kasputis T, Clough D, Noto F, Rychel K, Dye B and Shea LD: Microporous polymer scaffolds for the transplantation of embryonic stem cell derived pancreatic progenitors to a clinically translatable site for the treatment of type I diabetes. ACS Biomater Sci Eng. 4:1770–1778. 2018.

Pope JE, Denton CP, Johnson SR, Fernandez-Codina A, Hudson M and Nevskaya T: State-of-the-art evidence in the treatment of systemic sclerosis. Nat Rev Rheumatol. 19:212–226. 2023. View Article : Google Scholar

Rodnan GP and Fennell RH Jr: Progressive systemic sclerosis sine scleroderma. JAMA. 180:665–670. 1962. View Article : Google Scholar

Bairkdar M, Rossides M, Westerlind H, Hesselstrand R, Arkema EV and Holmqvist M: Incidence and prevalence of systemic sclerosis globally: A comprehensive systematic review and meta-analysis. Rheumatology (Oxford). 60:3121–3133. 2021. View Article : Google Scholar

Calderon LM and Pope JE: Scleroderma epidemiology update. Curr Opin Rheumatol. 33:122–127. 2021. View Article : Google Scholar

Lescoat A, Huang S, Carreira PE, Siegert E, de Vries-Bouwstra J, Distler JHW, Smith V, Del Galdo F, Anic B, Damjanov N, et al: Cutaneous manifestations, clinical characteristics, and prognosis of patients with systemic sclerosis sine scleroderma: Data from the international EUSTAR database. JAMA Dermatol. 159:837–847. 2023. View Article : Google Scholar

Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, et al: Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 354:2655–2666. 2006. View Article : Google Scholar

Distler O, Highland KB, Gahlemann M, Azuma A, Fischer A, Mayes MD, Raghu G, Sauter W, Girard M, Alves M, et al: Nintedanib for systemic sclerosis-associated interstitial lung disease. N Engl J Med. 380:2518–2528. 2019. View Article : Google Scholar

Rubin LJ, Badesch DB, Barst RJ, Galie N, Black CM, Keogh A, Pulido T, Frost A, Roux S and Leconte I: Bosentan therapy for pulmonary arterial hypertension. N Engl J Med. 346:896–903. 2002. View Article : Google Scholar

Jordan S, Distler JH, Maurer B, Huscher D, van Laar JM, Allanore Y and Distler O; EUSTAR Rituximab study group, : Effects and safety of rituximab in systemic sclerosis: An analysis from the European Scleroderma Trial and Research (EUSTAR) group. Ann Rheum Dis. 74:1188–1194. 2015. View Article : Google Scholar

Gholami S, Mazidi Z, Pahlavan S, Moslem F, Hosseini M, Taei A, Hesaraki M, Barekat M, Aghdami N and Baharvand H: A novel insight into endothelial and cardiac cells phenotype in systemic sclerosis using patient-derived induced pluripotent stem cell. Cell J. 23:273–287. 2021.

Vijayaraj P, Minasyan A, Durra A, Karumbayaram S, Mehrabi M, Aros CJ, Ahadome SD, Shia DW, Chung K, Sandlin JM, et al: Modeling progressive fibrosis with pluripotent stem cells identifies an anti-fibrotic small molecule. Cell Rep. 29:3488–3505. 2019. View Article : Google Scholar

Nathan S, Wang Y, D'ambrosio M, Paul R, Lyu H, Delic D, Bretschneider T, Falana K, Li L and Vijayaraj P: Comparative transcriptomic analysis validates iPSC derived in-vitro progressive fibrosis model as a screening tool for drug discovery and development in systemic sclerosis. Sci Rep. 14:244282024. View Article : Google Scholar

Kim Y, Nam Y, Rim YA and Ju JH: Anti-fibrotic effect of a selective estrogen receptor modulator in systemic sclerosis. Stem Cell Res Ther. 13:3032022. View Article : Google Scholar

Sawamoto N, Doi D, Nakanishi E, Sawamura M, Kikuchi T, Yamakado H, Taruno Y, Shima A, Fushimi Y, Okada T, et al: Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease. Nature. 641:971–977. 2025. View Article : Google Scholar

Sugimoto N, Kanda J, Nakamura S, Kitano T, Hishizawa M, Kondo T, Shimizu S, Shigemasa A, Hirai H, Arai Y, et al: iPLAT1: The first-in-human clinical trial of iPSC-derived platelets as a phase 1 autologous transfusion study. Blood. 140:2398–2402. 2022. View Article : Google Scholar

Hirami Y, Mandai M, Sugita S, Maeda A, Maeda T, Yamamoto M, Uyama H, Yokota S, Fujihara M, Igeta M, et al: Safety and stable survival of stem-cell-derived retinal organoid for 2 years in patients with retinitis pigmentosa. Cell Stem Cell. 30:1585–1596.e6. 2023. View Article : Google Scholar

Jebran AF, Seidler T, Tiburcy M, Daskalaki M, Kutschka I, Fujita B, Ensminger S, Bremmer F, Moussavi A, Yang H, et al: Engineered heart muscle allografts for heart repair in primates and humans. Nature. 639:503–511. 2025. View Article : Google Scholar

Imamura K, Izumi Y, Nagai M, Nishiyama K, Watanabe Y, Hanajima R, Egawa N, Ayaki T, Oki R, Fujita K, et al: Safety and tolerability of bosutinib in patients with amyotrophic lateral sclerosis (iDReAM study): A multicentre, open-label, dose-escalation phase 1 trial. EClinicalMedicine. 53:1017072022. View Article : Google Scholar