Current Stem Cell Research & TherapyCurrent Stem Cell Research & TherapyCurrent Stem Cell Research & Therapy1574-888X2212-3946Bentham Science64592210.2174/011574888X268740231002054459MedicineResearch ArticleMesenchymal Stem Cell Transplantation in Type 1 Diabetes Treatment: Current Advances and Future OpportunityLiuJieinfo@benthamscience.netWanXin-Xinginfo@benthamscience.netZhengSheng-Yuaninfo@benthamscience.netKhanMd.info@benthamscience.netHeHui-Honginfo@benthamscience.netFengYu-Xinginfo@benthamscience.netXiaoJing-Geinfo@benthamscience.netChenYuinfo@benthamscience.netHuXi-Mininfo@benthamscience.netZhangQiinfo@benthamscience.netXiongKuninfo@benthamscience.netDepartment of Endocrinology, Third Xiangya Hospital, Central South UniversityClinical Medicine Eight-year Program, 19 Grade, Xiangya School of Medicine, Central South University, Nature Study Society of BangladeshClinical Medicine Eight-year Program, 19 Grade, Xiangya School of Medicine, Central South UniversitDepartment of Anatomy and Neurobiology, School of Basic Medical Science, Central South UniversityDepartment of Anatomy and Neurobiology, School of Basic Medical Science, Central South Universit010920241991175118411012025Copyright ©; 2024, Bentham Science Publishers2024Bentham Science Publishershttps://journals.eco-vector.com/1574-888X/article/view/645922

:Type 1 Diabetes (T1D) is characterized by hyperglycemia, and caused by a lack of insulin secretion. At present there is no cure for T1D and patients are dependent on exogenous insulin for lifelong, which seriously affects their lives. Mesenchymal stem cells (MSCs) can be differentiated to β cell-like cells to rescue the secretion of insulin and reconstruct immunotolerance to preserve the function of islet β cells. Due to the higher proportion of children and adolescents in T1D patients, the efficacy and safety issue of the application of MSC’s transplant in T1D was primarily demonstrated and identified by human clinical trials in this review. Then we clarified the mechanism of MSCs to relieve the symptom of T1D and found out that UC-MSCs have no obvious advantage over the other types of MSCs, the autologous MSCs from BM or menstrual blood with less expanded ex vivo could be the better choice for clinical application to treat with T1D through documentary analysis. Finally, we summarized the advances of MSCs with different interventions such as genetic engineering in the treatment of T1D, and demonstrated the advantages and shortage of MSCs intervened by different treatments in the transplantation, which may enhance the clinical efficacy and overcome the shortcomings in the application of MSCs to T1D in future.

T1DMSCstransplantgenetic engineeringmesenchymal stem cellsmenstrual blood.Matos J, Matos I, Calha M, et al. Insights from bacteroides species in children with type 1 diabetes. Microorganisms 2021; 9(7): 1436. doi: 10.3390/microorganisms9071436 PMID: 34361871Jorge H, Duarte IC, Baptista C, Relvas AP, Castelo-Branco M. Trust-based decision-making in the health context discriminates biological risk profiles in type 1 diabetes. J Pers Med 2022; 12(8): 1236. doi: 10.3390/jpm12081236 PMID: 36013185Koehler N, Buhler L, Egger B, Gonelle-Gispert C. Multipotent mesenchymal stromal cells interact and support islet of langerhans viability and function. Front Endocrinol 2022; 13: 822191. doi: 10.3389/fendo.2022.822191 PMID: 35222280Xu G, Liu B, Sun Y, et al. Prevalence of diagnosed type 1 and type 2 diabetes among US adults in 2016 and 2017: Population based study. BMJ 2018; 362: k1497. doi: 10.1136/bmj.k1497 PMID: 30181166Marks BE, Wolfsdorf JI. Monitoring of paediatric type 1 diabetes. Curr Opin Pediatr 2022; 34(4): 391-9. doi: 10.1097/MOP.0000000000001136 PMID: 35836398Farthing P, Bally J, Rennie DC, Dietrich Leurer M, Holtslander L, Nour MA. Type 1 diabetes management responsibilities between adolescents with T1D and their parents: An integrative review. J Spec Pediatr Nurs 2022; 27(4): e12395. doi: 10.1111/jspn.12395 PMID: 36116027Bloomgarden Z, Schatz D. Small steps forward: Adjunctive therapy for T1D. J Diabetes 2022; 14(10): 642-5. doi: 10.1111/1753-0407.13326 PMID: 36205524Wan XX, Zhang DY, Khan MA, et al. Stem cell transplantation in the treatment of type 1 diabetes mellitus: From insulin replacement to beta-cell replacement. Front Endocrinol 2022; 13: 859638. doi: 10.3389/fendo.2022.859638 PMID: 35370989Yang R, Yang S, Zhao J, et al. Progress in studies of epidermal stem cells and their application in skin tissue engineering. Stem Cell Res Ther 2020; 11(1): 303. doi: 10.1186/s13287-020-01796-3 PMID: 32698863He L, Chen Z, Peng L, Tang B, Jiang H. Human stem cell models of polyglutamine diseases: Sources for disease models and cell therapy. Exp Neurol 2021; 337: 113573. doi: 10.1016/j.expneurol.2020.113573 PMID: 33347831Yang R, Liu F, Wang J, Chen X, Xie J, Xiong K. Epidermal stem cells in wound healing and their clinical applications. Stem Cell Res Ther 2019; 10(1): 229. doi: 10.1186/s13287-019-1312-z PMID: 31358069Fričová D, Korchak JA, Zubair AC. Challenges and translational considerations of mesenchymal stem/stromal cell therapy for Parkinson’s disease. NPJ Regen Med 2020; 5(1): 20. doi: 10.1038/s41536-020-00106-y PMID: 33298940Le Bastard Q, Chevallier P, Montassier E. Gut microbiome in allogeneic hematopoietic stem cell transplantation and specific changes associated with acute graft vs host disease. World J Gastroenterol 2021; 27(45): 7792-800. doi: 10.3748/wjg.v27.i45.7792 PMID: 34963742Hu XM, Zhang Q, Zhou RX, et al. Programmed cell death in stem cell-based therapy: Mechanisms and clinical applications. World J Stem Cells 2021; 13(5): 386-415. doi: 10.4252/wjsc.v13.i5.386 PMID: 34136072Yan WT, Zhao WJ, Hu XM, et al. PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons. Neural Regen Res 2023; 18(2): 357-63. PMID: 35900430Druey KM, Eisch AR, Cunningham-Rundles C. Autologous hematopoietic stem cell transplantation in Clarkson disease. J Allergy Clin Immunol Pract 2022; 11(1): 347-9. PMID: 36309188Hu XM, Li ZX, Zhang DY, et al. A systematic summary of survival and death signalling during the life of hair follicle stem cells. Stem Cell Res Ther 2021; 12(1): 453. doi: 10.1186/s13287-021-02527-y PMID: 34380571Loretelli C, Assi E, Seelam AJ, Ben Nasr M, Fiorina P. Cell therapy for type 1 diabetes. Expert Opin Biol Ther 2020; 20(8): 887-97. doi: 10.1080/14712598.2020.1748596 PMID: 32299257Silva IBB, Kimura CH, Colantoni VP, Sogayar MC. Stem cells differentiation into insulin-producing cells (IPCs): Recent advances and current challenges. Stem Cell Res Ther 2022; 13(1): 309. doi: 10.1186/s13287-022-02977-y PMID: 35840987Pastore I, Assi E, Ben Nasr M, et al. Hematopoietic stem cells in type 1 diabetes. Front Immunol 2021; 12: 694118. doi: 10.3389/fimmu.2021.694118 PMID: 34305929Nikoonezhad M, Lasemi MV, Alamdari S, et al. Treatment of insulin-dependent diabetes by hematopoietic stem cell transplantation. Transpl Immunol 2022; 75: 101682. doi: 10.1016/j.trim.2022.101682 PMID: 35926800Lim LY, Ching C, Kong D, Chan SY, Teo AKK. Generating pancreatic beta-like cells from human pluripotent stem cells. Methods Cell Biol 2022; 170: 127-46. doi: 10.1016/bs.mcb.2022.02.011 PMID: 35811096de Klerk E, Hebrok M. Stem cell-based clinical trials for diabetes mellitus. Front Endocrinol 2021; 12: 631463. doi: 10.3389/fendo.2021.631463 PMID: 33716982Zhang Q, Wan X, Hu X, et al. Targeting programmed cell death to improve stem cell therapy: Implications for treating diabetes and diabetes-related diseases. Front Cell Dev Biol 2021; 9: 809656. doi: 10.3389/fcell.2021.809656 PMID: 34977045Qin B, Zhang Q, Chen D, et al. Extracellular vesicles derived from mesenchymal stem cells: A platform that can be engineered. Histol Histopathol 2021; 36(6): 615-32. PMID: 33398872Singh P. MSC and HSPC coculture: Mimicking ex vivo bone marrow niche. Methods Mol Biol 2023; 2567: 181-9. doi: 10.1007/978-1-0716-2679-5_12 PMID: 36255702Lin YJ, Lee YW, Chang CW, Huang CC. 3D spheroids of umbilical cord blood MSC-derived schwann cells promote peripheral nerve regeneration. Front Cell Dev Biol 2020; 8: 604946. doi: 10.3389/fcell.2020.604946 PMID: 33392194Cao T, Chen H, Huang W, et al. hUC-MSC-mediated recovery of subacute spinal cord injury through enhancing the pivotal subunits β3 and γ2 of the GABA A receptor. Theranostics 2022; 12(7): 3057-78. doi: 10.7150/thno.72015 PMID: 35547766Bandekar M, Maurya DK, Sharma D, Sandur SK. Preclinical studies and clinical prospects of wharton’s jelly-derived MSC for treatment of acute radiation syndrome. Curr Stem Cell Rep 2021; 7(2): 85-94. doi: 10.1007/s40778-021-00188-4 PMID: 33936933Abo-Aziza FAM, Zaki AKA, Abo El-Maaty AM. Bone marrow-derived mesenchymal stem cell (BM-MSC): A tool of cell therapy in hydatid experimentally infected rats. Cell Regen 2019; 8(2): 58-71. doi: 10.1016/j.cr.2019.11.001 PMID: 31844519Zou W, Liu J, Jiao Y, et al. Human umbilical cord-derived mesenchymal stem cells promote repair of neonatal brain injury caused by hypoxia/ischemia in rats. Neural Regen Res 2022; 17(11): 2518-25. doi: 10.4103/1673-5374.339002 PMID: 35535905Moravcikova E, Meyer EM, Corselli M, Donnenberg VS, Donnenberg AD. Proteomic profiling of native unpassaged and culture‐expanded Mesenchymal Stromal Cells (MSC). Cytometry A 2018; 93(9): 894-904. doi: 10.1002/cyto.a.23574 PMID: 30211967Farrell MJ, Fisher MB, Huang AH, Shin JI, Farrell KM, Mauck RL. Functional properties of bone marrow-derived MSC-based engineered cartilage are unstable with very long-term in vitro culture. J Biomech 2014; 47(9): 2173-82. doi: 10.1016/j.jbiomech.2013.10.030 PMID: 24239005Deng B, Zhang X, Liang Y, et al. Nonadherent culture method promotes MSC-mediated vascularization in myocardial infarction via miR-519d/VEGFA pathway. Stem Cell Res Ther 2020; 11(1): 266. doi: 10.1186/s13287-020-01780-x PMID: 32616068Chatzistamatiou TK, Papassavas AC, Michalopoulos E, et al. Optimizing isolation culture and freezing methods to preserve Wharton’s jelly’s mesenchymal stem cell (MSC) properties: An MSC banking protocol validation for the hellenic cord blood bank. Transfusion 2014; 54(12): 3108-20. doi: 10.1111/trf.12743 PMID: 24894363Adamzyk C, Emonds T, Falkenstein J, et al. Different culture media affect proliferation, surface epitope expression, and differentiation of ovine MSC. Stem Cells Int 2013; 2013: 1-13. doi: 10.1155/2013/387324 PMID: 24228035Chen M, Zhao Y, Zhou L, et al. Exosomes derived from human umbilical cord mesenchymal stem cells enhance insulin sensitivity in insulin resistant human adipocytes. Curr Med Sci 2021; 41(1): 87-93. doi: 10.1007/s11596-021-2323-4 PMID: 33582911Li L, Shen S, Ouyang J, et al. Autologous hematopoietic stem cell transplantation modulates immunocompetent cells and improves β-cell function in Chinese patients with new onset of type 1 diabetes. J Clin Endocrinol Metab 2012; 97(5): 1729-36. doi: 10.1210/jc.2011-2188 PMID: 22419704Cai J, Wu Z, Xu X, et al. Umbilical cord mesenchymal stromal cell with autologous bone marrow cell transplantation in established type 1 diabetes: A pilot randomized controlled open-label clinical study to assess safety and impact on insulin secretion. Diabetes Care 2016; 39(1): 149-57. doi: 10.2337/dc15-0171 PMID: 26628416Liu Y, Hu J, Wang S. Mesenchymal stem cell-mediated treatment of oral diseases. Histol Histopathol 2014; 29(8): 1007-15. PMID: 24638842Yeung CK, Yan Y, Yan L, et al. Preclinical safety evaluation and tracing of human mesenchymal stromal cell spheroids following intravenous injection into cynomolgus monkeys. Biomaterials 2022; 289: 121759. doi: 10.1016/j.biomaterials.2022.121759 PMID: 36075143Torres Crigna A, Uhlig S, Elvers-Hornung S, Klüter H, Bieback K. Human adipose tissue-derived stromal cells suppress human, but not murine lymphocyte proliferation, via indoleamine 2,3- dioxygenase activity. Cells 2020; 9(11): 2419. doi: 10.3390/cells9112419 PMID: 33167329Nicotra T, Desnos A, Halimi J, et al. Mesenchymal stem/stromal cell quality control: Validation of mixed lymphocyte reaction assay using flow cytometry according to ICH Q2(R1). Stem Cell Res Ther 2020; 11(1): 426. doi: 10.1186/s13287-020-01947-6 PMID: 33004063Mckinnirey F, Herbert B, Vesey G, McCracken S. Immune modulation via adipose derived Mesenchymal Stem cells is driven by donor sex in vitro. Sci Rep 2021; 11(1): 12454. doi: 10.1038/s41598-021-91870-4 PMID: 34127731Jones OY, McCurdy D. Cell based treatment of autoimmune diseases in children. Front Pediatr 2022; 10: 855260. doi: 10.3389/fped.2022.855260 PMID: 35615628Garcia SG, Sandoval-Hellín N, Clos-Sansalvador M, et al. Mesenchymal stromal cells induced regulatory B cells are enriched in extracellular matrix genes and IL-10 independent modulators. Front Immunol 2022; 13: 957797. doi: 10.3389/fimmu.2022.957797 PMID: 36189264Farge D, Loisel S, Lansiaux P, Tarte K. Mesenchymal stromal cells for systemic sclerosis treatment. Autoimmun Rev 2021; 20(3): 102755. doi: 10.1016/j.autrev.2021.102755 PMID: 33476823Esquivel D, Mishra R, Srivastava A. Stem cell therapy offers a possible safe and promising alternative approach for treating vitiligo: A review. Curr Pharm Des 2020; 26(37): 4815-21. doi: 10.2174/1381612826666200730221446 PMID: 32744962Barros I, Marcelo A, Silva TP, et al. Mesenchymal stromal cells’ therapy for polyglutamine disorders: Where do we stand and Where should we go? Front Cell Neurosci 2020; 14: 584277. doi: 10.3389/fncel.2020.584277 PMID: 33132851Cho J, D’Antuono M, Glicksman M, Wang J, Jonklaas J. A review of clinical trials: Mesenchymal stem cell transplant therapy in type 1 and type 2 diabetes mellitus. Am J Stem Cells 2018; 7(4): 82-93. PMID: 30510843Bani Hamad FR, Rahat N, Shankar K, Tsouklidis N. Efficacy of stem cell application in diabetes mellitus: promising future therapy for diabetes and its complications. Cureus 2021; 13(2): e13563. doi: 10.7759/cureus.13563 PMID: 33815977Madani S, Amanzadi M, Aghayan HR, et al. Investigating the safety and efficacy of hematopoietic and mesenchymal stem cell transplantation for treatment of T1DM: A systematic review and meta- analysis. Syst Rev 2022; 11(1): 82. doi: 10.1186/s13643-022-01950-3 PMID: 35501872Carlsson PO, Schwarcz E, Korsgren O, Le Blanc K. Preserved β- cell function in type 1 diabetes by mesenchymal stromal cells. Diabetes 2015; 64(2): 587-92. doi: 10.2337/db14-0656 PMID: 25204974El-Badawy A, El-Badri N. Clinical efficacy of stem cell therapy for diabetes mellitus: A meta-analysis. PLoS One 2016; 11(4): e0151938. doi: 10.1371/journal.pone.0151938 PMID: 27073927Izadi M, Sadr Hashemi Nejad A, Moazenchi M, et al. Mesenchymal stem cell transplantation in newly diagnosed type-1 diabetes patients: A phase I/II randomized placebo-controlled clinical trial. Stem Cell Res Ther 2022; 13(1): 264. doi: 10.1186/s13287-022-02941-w PMID: 35725652Lu J, Shen S, Ling Q, et al. One repeated transplantation of allogeneic umbilical cord mesenchymal stromal cells in type 1 diabetes: An open parallel controlled clinical study. Stem Cell Res Ther 2021; 12(1): 340. doi: 10.1186/s13287-021-02417-3 PMID: 34112266Gao F, Wu DQ, Hu YH, et al. In vitro cultivation of islet-like cell clusters from human umbilical cord blood-derived mesenchymal stem cells. Transl Res 2008; 151(6): 293-302. doi: 10.1016/j.trsl.2008.03.003 PMID: 18514140Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol 2004; 10(20): 3016-20. doi: 10.3748/wjg.v10.i20.3016 PMID: 15378785Dave SD, Vanikar AV, Trivedi HL, Thakkar UG, Gopal SC, Chandra T. Novel therapy for insulin-dependent diabetes mellitus: Infusion of in vitro-generated insulin-secreting cells. Clin Exp Med 2015; 15(1): 41-5. doi: 10.1007/s10238-013-0266-1 PMID: 24317657Thakkar UG, Trivedi HL, Vanikar AV, Dave SD. Insulin-secreting adipose-derived mesenchymal stromal cells with bone marrow–derived hematopoietic stem cells from autologous and allogenic sources for type 1 diabetes mellitus. Cytotherapy 2015; 17(7): 940-7. doi: 10.1016/j.jcyt.2015.03.608 PMID: 25869301Chao KC, Chao KF, Fu YS, Liu SH. Islet-like clusters derived from mesenchymal stem cells in Wharton’s Jelly of the human umbilical cord for transplantation to control type 1 diabetes. PLoS One 2008; 3(1): e1451. doi: 10.1371/journal.pone.0001451 PMID: 18197261Karnieli O, Izhar-Prato Y, Bulvik S, Efrat S. Generation of insulin-producing cells from human bone marrow mesenchymal stem cells by genetic manipulation. Stem Cells 2007; 25(11): 2837-44. doi: 10.1634/stemcells.2007-0164 PMID: 17615265Boumaza I, Srinivasan S, Witt WT, et al. Autologous bone marrow-derived rat mesenchymal stem cells promote PDX-1 and insulin expression in the islets, alter T cell cytokine pattern and preserve regulatory T cells in the periphery and induce sustained normoglycemia. J Autoimmun 2009; 32(1): 33-42. doi: 10.1016/j.jaut.2008.10.004 PMID: 19062254Domouky AM, Hegab AS, Al-Shahat A, Raafat N. Mesenchymal stem cells and differentiated insulin producing cells are new horizons for pancreatic regeneration in type I diabetes mellitus. Int J Biochem Cell Biol 2017; 87: 77-85. doi: 10.1016/j.biocel.2017.03.018 PMID: 28385600Liu W, Yu M, Xie D, et al. Melatonin-stimulated MSC-derived exosomes improve diabetic wound healing through regulating macrophage M1 and M2 polarization by targeting the PTEN/AKT pathway. Stem Cell Res Ther 2020; 11(1): 259. doi: 10.1186/s13287-020-01756-x PMID: 32600435Hotchkiss KM, Clark NM, Olivares-Navarrete R. Macrophage response to hydrophilic biomaterials regulates MSC recruitment and T-helper cell populations. Biomaterials 2018; 182: 202-15. doi: 10.1016/j.biomaterials.2018.08.029 PMID: 30138783Babazadeh S, Nassiri SM, Siavashi V, Sahlabadi M, Hajinasrollah M, Zamani-Ahmadmahmudi M. Macrophage polarization by MSC-derived CXCL12 determines tumor growth. Cell Mol Biol Lett 2021; 26(1): 30. doi: 10.1186/s11658-021-00273-w PMID: 34174813Liu J, Li P, Zhu J, et al. Mesenchymal stem cell-mediated immunomodulation of recruited mononuclear phagocytes during acute lung injury: A high-dimensional analysis study. Theranostics 2021; 11(5): 2232-46. doi: 10.7150/thno.52514 PMID: 33500722de Castro LL, Lopes-Pacheco M, Weiss DJ, Cruz FF, Rocco PRM. Current understanding of the immunosuppressive properties of mesenchymal stromal cells. J Mol Med 2019; 97(5): 605-18. doi: 10.1007/s00109-019-01776-y PMID: 30903229Mázló A, Kovács R, Miltner N, et al. MSC-like cells increase ability of monocyte-derived dendritic cells to polarize IL-17-/IL-10-producing T cells via CTLA-4. iScience 2021; 24(4): 102312. doi: 10.1016/j.isci.2021.102312 PMID: 33855282Li W, Huang Y, Gao C, Zhu Z, Dai G. Mesenchymal Stem Cell (MSC) transplantation accompanied by activation of invariant natural killer T cells further ameliorates post-infarct cardiac remodeling in mice. Discov Med 2021; 32(166): 51-63. PMID: 35219346Zhao J, Chen J, Huang F, et al. Human gingiva tissue-derived MSC ameliorates immune-mediated bone marrow failure of aplastic anemia via suppression of Th1 and Th17 cells and enhancement of CD4+Foxp3+ regulatory T cells differentiation. Am J Transl Res 2019; 11(12): 7627-43. PMID: 31934306Liu C, Zhang Y, Chen F, et al. Immunopathology in schistosomiasis is regulated by TLR2,4- and IFN-γ-activated MSC through modulating Th1/Th2 responses. Stem Cell Res Ther 2020; 11(1): 217. doi: 10.1186/s13287-020-01735-2 PMID: 32503644Torrecillas-Baena B, Gálvez-Moreno MÁ, Quesada-Gómez JM, Dorado G, Casado-Díaz A. Influence of Dipeptidyl Peptidase-4 (DPP4) on Mesenchymal Stem-Cell (MSC) biology: Implications for regenerative medicine - Review. Stem Cell Rev Rep 2022; 18(1): 56-76. doi: 10.1007/s12015-021-10285-w PMID: 34677817Holmes D. MSC transplant prevents β-cell dysfunction. Nat Rev Endocrinol 2014; 10(12): 701. doi: 10.1038/nrendo.2014.172 PMID: 25265979Caplan HW, Prabhakara KS, Toledano Furman NE, et al. Human-derived Treg and MSC combination therapy may augment immunosuppressive potency in vitro, but did not improve blood brain barrier integrity in an experimental rat traumatic brain injury model. PLoS One 2021; 16(5): e0251601. doi: 10.1371/journal.pone.0251601 PMID: 34038436Zanetti SR, Romecin PA, Vinyoles M, et al. Bone marrow MSC from pediatric patients with B-ALL highly immunosuppress T- cell responses but do not compromise CD19-CAR T-cell activity. J Immunother Cancer 2020; 8(2): e001419. doi: 10.1136/jitc-2020-001419 PMID: 32868394Daryabor G, Shiri EH, Amirghofran Z, Kamali-Sarvestani E. In vitro-derived insulin-producing cells modulate Th1 immune responses and induce IL-10 in streptozotocin-induced mouse model of pancreatic insulitis. Hepatobiliary Pancreat Dis Int 2021; 20(4): 376-82. doi: 10.1016/j.hbpd.2021.03.008 PMID: 33879406Li L, Hui H, Jia X, et al. Infusion with human bone marrow-derived mesenchymal stem cells improves β-cell function in patients and non-obese mice with severe diabetes. Sci Rep 2016; 6(1): 37894. doi: 10.1038/srep37894 PMID: 27905403Dazzi F, Horwood NJ. Potential of mesenchymal stem cell therapy. Curr Opin Oncol 2007; 19(6): 650-5. doi: 10.1097/CCO.0b013e3282f0e116 PMID: 17906466Djouad F, Plence P, Bony C, et al. Immunosuppressive effect of mesenchymal stem cells favors tumor growth in allogeneic animals. Blood 2003; 102(10): 3837-44. doi: 10.1182/blood-2003-04-1193 PMID: 12881305Maccario R, Podestà M, Moretta A, et al. Interaction of human mesenchymal stem cells with cells involved in alloantigen-specific immune response favors the differentiation of CD4+ T-cell subsets expressing a regulatory/suppressive phenotype. Haematologica 2005; 90(4): 516-25. PMID: 15820948Corcione A, Benvenuto F, Ferretti E, et al. Human mesenchymal stem cells modulate B-cell functions. Blood 2006; 107(1): 367-72. doi: 10.1182/blood-2005-07-2657 PMID: 16141348Iwamoto Y, Kimura T, Iwamoto H, et al. Incidence of endocrine-related immune-related adverse events in Japanese subjects with various types of cancer. Front Endocrinol 2023; 14: 1079074. doi: 10.3389/fendo.2023.1079074 PMID: 36755909Kawada-Horitani E, Kita S, Okita T, et al. Human adipose-derived mesenchymal stem cells prevent type 1 diabetes induced by immune checkpoint blockade. Diabetologia 2022; 65(7): 1185-97. doi: 10.1007/s00125-022-05708-3 PMID: 35511238Wang Y-D, Yang X-F, Wen L, et al. Exosomes derived from bone marrow mesenchymal stem cells inhibit neuroinflammation after traumatic brain injury. Neural Regen Res 2022; 17(12): 2717-24. doi: 10.4103/1673-5374.339489 PMID: 35662219Jia Y-J, Zhou Y, Wen L-L, et al. Exosomes derived from bone marrow mesenchymal stem cells protect the injured spinal cord by inhibiting pericyte pyroptosis. Neural Regen Res 2022; 17(1): 194-202. doi: 10.4103/1673-5374.314323 PMID: 34100456Davies LC, Alm JJ, Heldring N, et al. Type 1 diabetes mellitus donor mesenchymal stromal cells exhibit comparable potency to healthy controls in vitro. Stem Cells Transl Med 2016; 5(11): 1485-95. doi: 10.5966/sctm.2015-0272 PMID: 27412884Gerace D, Martiniello-Wilks R, Habib R, et al. Ex vivo expansion of murine msc impairs transcription factor-induced differentiation into pancreatic β -cells. Stem Cells Int 2019; 2019: 1-15. doi: 10.1155/2019/1395301 PMID: 30956666Sun YL, Shang LR, Liu RH, et al. Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes. World J Stem Cells 2022; 14(1): 104-16. doi: 10.4252/wjsc.v14.i1.104 PMID: 35126831Mo Y, Wang Z, Gao J, et al. Comparative study of three types of mesenchymal stem cell to differentiate into pancreatic β‑like cells in vitro. Exp Ther Med 2021; 22(3): 936. doi: 10.3892/etm.2021.10368 PMID: 34335885Zhang W, Ling Q, Wang B, et al. Comparison of therapeutic effects of mesenchymal stem cells from umbilical cord and bone marrow in the treatment of type 1 diabetes. Stem Cell Res Ther 2022; 13(1): 406. doi: 10.1186/s13287-022-02974-1 PMID: 35941696Song L, Gou W, Wang J, et al. Overexpression of alpha-1 antitrypsin in mesenchymal stromal cells improves their intrinsic biological properties and therapeutic effects in nonobese diabetic mice. Stem Cells Transl Med 2021; 10(2): 320-31. doi: 10.1002/sctm.20-0122 PMID: 32945622Bao Y, Zhao Z, Gao H. Effect of hTIMP‐1 overexpression in human umbilical cord mesenchymal stem cells on the repair of pancreatic islets in type‐1 diabetic mice. Cell Biol Int 2021; 45(5): 1038-49. doi: 10.1002/cbin.11548 PMID: 33404139Lee HS, Song S, Shin DY, et al. Enhanced effect of human mesenchymal stem cells expressing human TNF-αR-Fc and HO-1 gene on porcine islet xenotransplantation in humanized mice. Xenotransplantation 2018; 25(1): e12342. doi: 10.1111/xen.12342 PMID: 29135052Boroujeni ZN, Aleyasin A. Insulin producing cells established using non-integrated lentiviral vector harboring PDX1 gene. World J Stem Cells 2013; 5(4): 217-28. doi: 10.4252/wjsc.v5.i4.217 PMID: 24179609Gaudreau MC, Gudi RR, Li G, Johnson BM, Vasu C. Gastrin producing syngeneic mesenchymal stem cells protect non-obese diabetic mice from type 1 diabetes. Autoimmunity 2022; 55(2): 95-108. doi: 10.1080/08916934.2021.2012165 PMID: 34882054Guo QS, Zhu MY, Wang L, et al. Combined transfection of the three transcriptional factors, PDX-1, NeuroD1, and MafA, causes differentiation of bone marrow mesenchymal stem cells into insulin-producing cells. Exp Diabetes Res 2012; 2012: 672013. PMID: 22761608