Skip to main content

Advertisement

SpringerLink
Log in

From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Loss and functional failure of pancreatic β-cells results in disruption of glucose homeostasis and progression of diabetes. Although whole pancreas or pancreatic islet transplantation serves as a promising approach for β-cell replenishment and diabetes therapy, the severe scarcity of donor islets makes it unattainable for most diabetic patients. Stem cells, particularly induced pluripotent stem cells (iPSCs), are promising for the treatment of diabetes owing to their self-renewal capacity and ability to differentiate into functional β-cells. In this review, we first introduce the development of functional β-cells and their heterogeneity and then turn to highlight recent advances in the generation of β-cells from stem cells and their potential applications in disease modeling, drug discovery and clinical therapy. Finally, we have discussed the current challenges in developing stem cell-based therapeutic strategies for improving the treatment of diabetes. Although some significant technical hurdles remain, stem cells offer great hope for patients with diabetes and will certainly transform future clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

No datasets were generated or analysed during the current study.

References

  1. Sun H, Saeedi P, Karuranga S, Pinkepank M, Ogurtsova K, Duncan BB, Stein C, Basit A, Chan JCN, Mbanya JC, Pavkov ME, Ramachandaran A, Wild SH, James S, Herman WHH, Zhang P, Bommer C, Kuo SH, Boyko EJJ, Magliano DJ (2022) IDF Diabetes Atlas: Global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Practice. https://doi.org/10.1016/j.diabres.2021.109119

    Article  Google Scholar 

  2. ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D, Collins BS, Hilliard ME, Isaacs D, Johnson EL, Kahan S, Khunti K, Leon J, Lyons SK, Perry ML, Prahalad P, Pratley RE, Seley JJ, Stanton RC, Gabbay RA, Assoc AD (2023) Classification and diagnosis of diabetes. Diabetes Care 46:S19–S40. https://doi.org/10.2337/dc23-S002

    Article  CAS  PubMed  Google Scholar 

  3. He SY, Yu XQ, Cui DX, Liu Y, Yang SS, Zhang HM, Hu WX, Su ZG (2023) Nuclear factor-Y mediates pancreatic beta-cell compensation by repressing reactive oxygen species-induced apoptosis under metabolic stress. Chin Med J 136:922–932. https://doi.org/10.1097/Cm9.0000000000002645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dal Canto E, Ceriello A, Ryden L, Ferrini M, Hansen TB, Schnell O, Standl E, Beulens JWJ (2019) Diabetes as a cardiovascular risk factor: an overview of global trends of macro and micro vascular complications. Eur J Prev Cardiol 26:25–32. https://doi.org/10.1177/2047487319878371

    Article  Google Scholar 

  5. Zhang XP, Deng D, Cui DX, Liu Y, He SY, Zhang HM, Xie YR, Yu XQ, Yang SS, Chen YL, Su ZG (2022) Cholesterol sulfate exerts protective effect on pancreatic beta-cells by regulating beta-cell mass and insulin secretion. Front Pharmacol. https://doi.org/10.3389/fphar.2022.840406

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zhang YJ, Guan QY, Liu Y, Zhang YW, Chen YL, Chen JL, Liu YL, Su ZG (2018) Regulation of hepatic gluconeogenesis by nuclear factor Y transcription factor in mice. J Biol Chem 293:7894–7904. https://doi.org/10.1074/jbc.RA117.000508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ahmad E, Lim S, Lamptey R, Webb DR, Davies MJ (2022) Type 2 diabetes. Lancet 400:1803–1820. https://doi.org/10.1016/S0140-6736(22)01655-5

    Article  PubMed  Google Scholar 

  8. Satin LS, Soleimanpour SA, Walker EM (2021) New aspects of diabetes research and therapeutic development. Pharmacol Rev 73:1001–1015. https://doi.org/10.1124/pharmrev.120.000160

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Liu Y, He SY, Zhou RX, Zhang XP, Yang SS, Deng D, Zhang CX, Yu XQ, Chen YL, Su ZG (2021) Nuclear factor-Y in mouse pancreatic beta-cells plays a crucial role in glucose homeostasis by regulating beta-cell mass and insulin secretion. Diabetes 70:1703–1716. https://doi.org/10.2337/db20-1238

    Article  CAS  PubMed  Google Scholar 

  10. Rorsman P, Ashcroft FM (2018) Pancreatic beta-cell electrical activity and insulin secretion: of mice and men. Physiol Rev 98:117–214. https://doi.org/10.1152/physrev.00008.2017

    Article  CAS  PubMed  Google Scholar 

  11. Herold KC, Vignali DAA, Cooke A, Bluestone JA (2013) Type 1 diabetes: translating mechanistic observations into effective clinical outcomes. Nat Rev Immunol 13:243–256. https://doi.org/10.1038/nri3422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Cui D, Feng X, Lei S, Zhang H, Hu W, Yang S, Yu X, Su Z (2024) Pancreatic beta-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes. Chin Med J (Engl). https://doi.org/10.1097/CM9.0000000000003034

    Article  PubMed  Google Scholar 

  13. Zhang X, Yang S, Chen J, Su Z (2018) Unraveling the regulation of hepatic gluconeogenesis. Front Endocrinol (Lausanne) 9:802. https://doi.org/10.3389/fendo.2018.00802

    Article  PubMed  Google Scholar 

  14. Murphy R, Ellard S, Hattersley AT (2008) Clinical implications of a molecular genetic classification of monogenic beta-cell diabetes. Nat Clin Pract Endocrinol Metab 4:200–213. https://doi.org/10.1038/ncpendmet0778

    Article  CAS  PubMed  Google Scholar 

  15. Basile G, Qadir MMF, Mauvais-Jarvis F, Vetere A, Shoba V, Modell AE, Pastori RL, Russ HA, Wagner BK, Dominguez-Bendala J (2022) Emerging diabetes therapies: bringing back the?-cells. Molecular Metabolism. https://doi.org/10.1016/j.molmet.2022.101477

    Article  PubMed  PubMed Central  Google Scholar 

  16. Gruessner AC, Gruessner RW (2016) Long-term outcome after pancreas transplantation: a registry analysis. Curr Opin Organ Transplant 21:377–385. https://doi.org/10.1097/MOT.0000000000000331

    Article  PubMed  Google Scholar 

  17. Stratta RJ, Farney AC, Fridell JA (2022) Analyzing outcomes following pancreas transplantation: definition of a failure or failure of a definition. Am J Transplant 22:1523–1526. https://doi.org/10.1111/ajt.17003

    Article  PubMed  PubMed Central  Google Scholar 

  18. Shapiro AM, Lakey JR, Ryan EA, Korbutt GS, Toth E, Warnock GL, Kneteman NM, Rajotte RV (2000) Islet transplantation in seven patients with type 1 diabetes mellitus using a glucocorticoid-free immunosuppressive regimen. N Engl J Med 343:230–238. https://doi.org/10.1056/NEJM200007273430401

    Article  CAS  PubMed  Google Scholar 

  19. Marfil-Garza BA, Shapiro AMJ, Kin T (2021) Clinical islet transplantation: current progress and new frontiers. J Hepatobiliary Pancreat Sci 28:243–254. https://doi.org/10.1002/jhbp.891

    Article  PubMed  Google Scholar 

  20. Salib A, Cayabyab F, Yoshihara E (2022) Stem cell-derived islets for type 2 diabetes. Int J Mol Sci. https://doi.org/10.3390/ijms23095099

    Article  PubMed  PubMed Central  Google Scholar 

  21. Liu G, David BT, Trawczynski M, Fessler RG (2020) Advances in pluripotent stem cells: history, mechanisms, technologies, and applications. Stem Cell Rev Rep 16:3–32. https://doi.org/10.1007/s12015-019-09935-x

    Article  PubMed  Google Scholar 

  22. Campbell JE, Newgard CB (2021) Mechanisms controlling pancreatic islet cell function in insulin secretion. Nat Rev Mol Cell Biol 22:142–158. https://doi.org/10.1038/s41580-020-00317-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tritschler S, Theis FJ, Lickert H, Böttcher A (2017) Systematic single-cell analysis provides new insights into heterogeneity and plasticity of the pancreas. Mol Metab 6:974–990. https://doi.org/10.1016/j.molmet.2017.06.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Roscioni SS, Migliorini A, Gegg M, Lickert H (2016) Impact of islet architecture on β-cell heterogeneity, plasticity and function. Nat Rev Endocrinol 12:695–709. https://doi.org/10.1038/nrendo.2016.147

    Article  CAS  PubMed  Google Scholar 

  25. Pan FC, Wright C (2011) Pancreas organogenesis: from bud to plexus to gland. Dev Dyn 240:530–565. https://doi.org/10.1002/dvdy.22584

    Article  CAS  PubMed  Google Scholar 

  26. Shih HP, Wang A, Sander M (2013) Pancreas organogenesis: from lineage determination to morphogenesis. Annu Rev Cell Dev Biol 29:81–105. https://doi.org/10.1146/annurev-cellbio-101512-122405

    Article  CAS  PubMed  Google Scholar 

  27. Collombat P, Mansouri A, Hecksher-Sorensen J, Serup P, Krull J, Gradwohl G, Gruss P (2003) Opposing actions of Arx and Pax4 in endocrine pancreas development. Genes Dev 17:2591–2603. https://doi.org/10.1101/gad.269003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Barsby T, Otonkoski T (2022) Maturation of beta cells: lessons from in vivo and in vitro models. Diabetologia 65:917–930. https://doi.org/10.1007/s00125-022-05672-y

    Article  PubMed  PubMed Central  Google Scholar 

  29. Nishimura W, Iwasa H, Tumurkhuu M (2022) Role of the transcription Factor MAFA in the maintenance of pancreatic β-Cells. Int J Mole Sci. https://doi.org/10.3390/ijms23094478

    Article  Google Scholar 

  30. Jennings RE, Berry AA, Strutt JP, Gerrard DT, Hanley NA (2015) Human pancreas development. Development 142:3126–3137. https://doi.org/10.1242/dev.120063

    Article  CAS  PubMed  Google Scholar 

  31. Nair G, Hebrok M (2015) Islet formation in mice and men: lessons for the generation of functional insulin-producing beta-cells from human pluripotent stem cells. Curr Opin Genet Dev 32:171–180. https://doi.org/10.1016/j.gde.2015.03.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Russell R, Carnese PP, Hennings TG, Walker EM, Russ HA, Liu JS, Giacometti S, Stein R, Hebrok M (2020) Loss of the transcription factor MAFB limits β-cell derivation from human PSCs. Nat Commun 11:2742. https://doi.org/10.1038/s41467-020-16550-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Arda HE, Li L, Tsai J, Torre EA, Rosli Y, Peiris H, Spitale RC, Dai C, Gu X, Qu K, Wang P, Wang J, Grompe M, Scharfmann R, Snyder MS, Bottino R, Powers AC, Chang HY, Kim SK (2016) Age-dependent pancreatic gene regulation reveals mechanisms governing human β cell function. Cell Metab 23:909–920. https://doi.org/10.1016/j.cmet.2016.04.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Cyphert HA, Walker EM, Hang Y, Dhawan S, Haliyur R, Bonatakis L, Avrahami D, Brissova M, Kaestner KH, Bhushan A, Powers AC, Stein R (2019) Examining how the MAFB transcription factor affects islet β-cell function postnatally. Diabetes 68:337–348. https://doi.org/10.2337/db18-0903

    Article  CAS  PubMed  Google Scholar 

  35. Ma Z, Zhang X, Zhong W, Yi H, Chen X, Zhao Y, Ma Y, Song E, Xu T (2023) Deciphering early human pancreas development at the single-cell level. Nat Commun 14:5354. https://doi.org/10.1038/s41467-023-40893-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Miranda MA, Macias-Velasco JF, Lawson HA (2021) Pancreatic (β-cell heterogeneity in health and diabetes: classes, sources, and subtypes. Am J Physiol-Endocrinol Metab 320:E716–E731. https://doi.org/10.1152/ajpendo.00649.2020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Giordano E, Bosco D, Cirulli V, Meda P (1991) Repeated glucose stimulation reveals distinct and lasting secretion patterns of individual rat pancreatic B cells. J Clin Invest 87:2178–2185. https://doi.org/10.1172/jci115251

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Salinno C, Cota P, Bastidas-Ponce A, Tarquis-Medina M, Lickert H, Bakhti M (2019) β-cell maturation and identity in health and disease. Int J Mole Sci. https://doi.org/10.3390/ijms20215417

    Article  Google Scholar 

  39. Dominguez-Gutierrez G, Xin YR, Gromada J (2019) Heterogeneity of human pancreatic beta-cells. Mol Metab 27:S7–S14. https://doi.org/10.1016/j.molmet.2019.06.015

    Article  CAS  PubMed Central  Google Scholar 

  40. Dorrell C, Schug J, Canaday PS, Russ HA, Tarlow BD, Grompe MT, Horton T, Hebrok M, Streeter PR, Kaestner KH, Grompe M (2016) Human islets contain four distinct subtypes of β cells. Nat Commun 7:11756. https://doi.org/10.1038/ncomms11756

    Article  PubMed  PubMed Central  Google Scholar 

  41. Johnston NR, Mitchell RK, Haythorne E, Pessoa MP, Semplici F, Ferrer J, Piemonti L, Marchetti P, Bugliani M, Bosco D, Berishvili E, Duncanson P, Watkinson M, Broichhagen J, Trauner D, Rutter GA, Hodson DJ (2016) Beta cell hubs dictate pancreatic islet responses to glucose. Cell Metab 24:389–401. https://doi.org/10.1016/j.cmet.2016.06.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Bader E, Migliorini A, Gegg M, Moruzzi N, Gerdes J, Roscioni SS, Bakhti M, Brandl E, Irmler M, Beckers J, Aichler M, Feuchtinger A, Leitzinger C, Zischka H, Wang-Sattler R, Jastroch M, Tschöp M, Machicao F, Staiger H, Häring HU, Chmelova H, Chouinard JA, Oskolkov N, Korsgren O, Speier S, Lickert H (2016) Identification of proliferative and mature β-cells in the islets of Langerhans. Nature 535:430. https://doi.org/10.1038/nature18624

    Article  CAS  PubMed  Google Scholar 

  43. Li X, Yang KY, Chan VW, Leung KT, Zhang XB, Wong AS, Chong CCN, Wang CC, Ku M, Lui KO (2020) Single-Cell RNA-Seq Reveals that CD9 Is a negative marker of glucose-responsive pancreatic beta-like cells derived from human pluripotent stem cells. Stem Cell Reports 15:1111–1126. https://doi.org/10.1016/j.stemcr.2020.09.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Dror E, Fagnocchi L, Weqert V, Apostle S, Grimaldi B, Gruber T, Panzeri I, Heyne S, Hoffler KD, Kreiner V, Ching RG, Lu TTH, Semwal A, Johnson B, Senapati P, Lempradl A, Schones D, Imhof A, Shen H, Pospisilik JA (2023) Epigenetic dosage identifies two major and functionally distinct j3 cell subtypes. Cell Metab 35:821. https://doi.org/10.1016/j.cmet.2023.03.008

    Article  CAS  PubMed  Google Scholar 

  45. Aldous N, Moin AM, Abdelalim EM (2023) Pancreatic β-cell heterogeneity in adult human islets and stem cell-derived islets. Cell Mol Life Sci. https://doi.org/10.1007/s00018-023-04815-7

    Article  PubMed  PubMed Central  Google Scholar 

  46. Sarkar A, Saha S, Paul A, Maji A, Roy P, Maity TK (2021) Understanding stem cells and its pivotal role in regenerative medicine. Life Sci. https://doi.org/10.1016/j.lfs.2021.119270

    Article  PubMed  Google Scholar 

  47. Volarevic V, Markovic BS, Gazdic M, Volarevic A, Jovicic N, Arsenijevic N, Armstrong L, Djonov V, Lako M, Stojkovic M (2018) Ethical and safety issues of stem cell-based therapy. Int J Med Sci 15:36–45. https://doi.org/10.7150/ijms.21666

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Keller GM (1995) In-vitro differentiation of embryonic stem-cells. Curr Opin Cell Biol 7:862–869. https://doi.org/10.1016/0955-0674(95)80071-9

    Article  CAS  PubMed  Google Scholar 

  49. Lumelsky N, Blondel O, Laeng P, Velasco I, Ravin R, McKay R (2001) Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets. Science 292:1389–1394. https://doi.org/10.1126/science.1058866

    Article  CAS  PubMed  Google Scholar 

  50. Rajagopal J, Anderson WJ, Kume S, Martinez OI, Melton DA (2003) Insulin staining of ES cell progeny from insulin uptake. Science 299:363–363

    Article  PubMed  Google Scholar 

  51. D’Amour KA, Agulnick AD, Eliazer S, Kelly OG, Kroon E, Baetge EE (2005) Efficient differentiation of human embryonic stem cells to definitive endoderm. Nat Biotechnol 23:1534–1541. https://doi.org/10.1038/nbt1163

    Article  CAS  PubMed  Google Scholar 

  52. D’Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol 24:1392–1401. https://doi.org/10.1038/nbt1259

    Article  CAS  PubMed  Google Scholar 

  53. Jiang JJ, Au M, Lu KH, Eshpeter A, Korbutt G, Fisk G, Majumdar AS (2007) Generation of insulin-producing islet-like clusters from human embryonic stem cells. Stem Cells 25:1940–1953. https://doi.org/10.1634/stemcells.2006-0761

    Article  CAS  PubMed  Google Scholar 

  54. Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O’Dwyer S, Quiskamp N, Mojibian M, Albrecht T, Yang YH, Johnson JD, Kieffer TJ (2014) Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol 32:1121–1133. https://doi.org/10.1038/nbt.3033

    Article  CAS  PubMed  Google Scholar 

  55. Pagliuca FW, Millman JR, Gurtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA (2014) Generation of functional human pancreatic beta cells in vitro. Cell 159:428–439. https://doi.org/10.1016/j.cell.2014.09.040

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Nair GG, Liu JS, Russ HA, Tran S, Saxton MS, Chen R, Juang C, Li ML, Nguyen VQ, Giacometti S, Puri S, Xing Y, Wang Y, Szot GL, Oberholzer J, Bhushan A, Hebrok M (2019) Recapitulating endocrine cell clustering in culture promotes maturation of human stem-cell-derived beta cells. Nat Cell Biol 21:263–274. https://doi.org/10.1038/s41556-018-0271-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Golchin A, Chatziparasidou A, Ranjbarvan P, Niknam Z, Ardeshirylajimi A (2021) Embryonic stem cells in clinical trials: current overview of developments and challenges. Adv Exp Med Biol 1312:19–37. https://doi.org/10.1007/5584_2020_592

    Article  CAS  PubMed  Google Scholar 

  58. Maxwell KG, Millman JR (2021) Applications of iPSC-derived beta cells from patients with diabetes. Cell Rep Med 2:100238. https://doi.org/10.1016/j.xcrm.2021.100238

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Agrawal A, Narayan G, Gogoi R, Thummer RP (2021) Recent advances in the generation of β-cells from induced pluripotent stem cells as a potential cure for diabetes mellitus. Adv Exp Med Biol 1347:1–27. https://doi.org/10.1007/5584_2021_653

    Article  CAS  PubMed  Google Scholar 

  60. Loretelli C, Assi E, Seelam AJ, Ben Nasr M, Fiorina P (2020) Cell therapy for type 1 diabetes. Expert Opin Biol Ther 20:887–897. https://doi.org/10.1080/14712598.2020.1748596

    Article  CAS  PubMed  Google Scholar 

  61. Veres A, Faust AL, Bushnell HL, Engquist EN, Kenty JHR, Harb G, Poh YC, Sintov E, Gurtler M, Pagliuca FW, Peterson QP, Melton DA (2019) Charting cellular identity during human in vitro beta-cell differentiation. Nature 569:368. https://doi.org/10.1038/s41586-019-1168-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Augsornworawat P, Maxwell KG, Velazco-Cruz L, Millman JR (2020) Single-Cell Transcriptome Profiling Reveals β Cell Maturation in Stem Cell-Derived Islets after Transplantation. Cell Rep 32:8. https://doi.org/10.1016/j.celrep.2020.108067

    Article  CAS  Google Scholar 

  63. Velazco-Cruz L, Song J, Maxwell KG, Goedegebuure MM, Augsornworawat P, Hogrebe NJ, Millman JR (2019) Acquisition of dynamic function in human stem cell-derived beta cells. Stem Cell Reports 12:351–365. https://doi.org/10.1016/j.stemcr.2018.12.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Hogrebe NJ, Augsornworawat P, Maxwell KG, Velazco-Cruz L, Millman JR (2020) Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells. Nat Biotechnol 38:460–470. https://doi.org/10.1038/s41587-020-0430-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Maxwell KG, Augsornworawat P, Velazco-Cruz L, Kim MH, Asada R, Hogrebe NJ, Morikawa S, Urano F, Millman JR (2020) Gene-edited human stem cell-derived beta cells from a patient with monogenic diabetes reverse preexisting diabetes in mice. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aax9106

    Article  PubMed  PubMed Central  Google Scholar 

  66. Yoshihara E, O’Connor C, Gasser E, Wei Z, Oh TG, Tseng TW, Wang D, Cayabyab F, Dai Y, Yu RT, Liddle C, Atkins AR, Downes M, Evans RM (2020) Immune-evasive human islet-like organoids ameliorate diabetes. Nature 586:606–611. https://doi.org/10.1038/s41586-020-2631-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Parent AV, Ashe S, Nair GG, Li ML, Chavez J, Liu JS, Zhong YP, Streeter PR, Hebrok M (2022) Development of a scalable method to isolate subsets of stem cell-derived pancreatic islet cells. Stem Cell Reports 17:979–992. https://doi.org/10.1016/j.stemcr.2022.02.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Sui L, Xin Y, Du Q, Georgieva D, Diedenhofen G, Haataja L, Su Q, Zuccaro MV, Kim J, Fu J, Xing Y, He Y, Baum D, Goland RS, Wang Y, Oberholzer J, Barbetti F, Arvan P, Kleiner S, Egli D (2021) Reduced replication fork speed promotes pancreatic endocrine differentiation and controls graft size. JCI Insight. https://doi.org/10.1172/jci.insight.141553

    Article  PubMed  PubMed Central  Google Scholar 

  69. Shilleh AH, Beard S, Russ HA (2023) Enrichment of stem cell-derived pancreatic beta-like cells and controlled graft size through pharmacological removal of proliferating cells. Stem Cell Reports 18:1284–1294. https://doi.org/10.1016/j.stemcr.2023.05.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Guan JY, Wang G, Wang JL, Zhang ZY, Fu Y, Cheng L, Meng GF, Lyu YL, Zhu JL, Li YQ, Wang YL, Liuyang SJ, Liu B, Yang ZR, He HJ, Zhong XX, Chen QJ, Zhang X, Sun SC, Lai WF, Shi Y, Liu LL, Wang LP, Li C, Lu SC, Deng HK (2022) Chemical reprogramming of human somatic cells to pluripotent stem cells. Nature 605:325. https://doi.org/10.1038/s41586-022-04593-5

    Article  CAS  PubMed  Google Scholar 

  71. Du YY, Liang Z, Wang S, Sun D, Wang XF, Liew SY, Lu SY, Wu SS, Jiang Y, Wang YQ, Zhang BY, Yu WH, Lu Z, Pu Y, Zhang Y, Long HT, Xiao SS, Liang R, Zhang ZY, Guan JY, Wang JL, Ren HX, Wei YL, Zhao JX, Sun SC, Liu TL, Meng GF, Wang L, Gu JB, Wang T, Liu YN, Li C, Tang C, Shen ZY, Peng XZ, Deng HK (2022) Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates. Nat Med 28:2725. https://doi.org/10.1038/s41591-021-01645-7

    Article  CAS  Google Scholar 

  72. Liang Z, Sun D, Lu SY, Lei ZJ, Wang SS, Luo ZF, Zhan JQ, Wu SS, Jiang Y, Lu Z, Sun SC, Shi YY, Long HT, Wei YL, Yu WH, Wang ZH, Yi LS, Zhang Y, Sun WY, Fang XF, Li YY, Lu SF, Lv JY, Sui WG, Shen ZY, Peng XZ, Du YY, Deng HK (2023) Implantation underneath the abdominal anterior rectus sheath enables effective and functional engraftment of stem-cell-derived islets. Nat Metab. https://doi.org/10.1038/s42255-022-00713-7

    Article  PubMed  PubMed Central  Google Scholar 

  73. Ghoneim MA, Refaie AF, Elbassiouny BL, Gabr MM, Zakaria MM (2020) From mesenchymal stromal/stem cells to insulin-producing cells: progress and challenges. Stem Cell Rev Rep 16:1156–1172. https://doi.org/10.1007/s12015-020-10036-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Wu X, Jiang J, Gu Z, Zhang J, Chen Y, Liu X (2020) Mesenchymal stromal cell therapies: immunomodulatory properties and clinical progress. Stem Cell Res Ther 11:345. https://doi.org/10.1186/s13287-020-01855-9

    Article  PubMed  PubMed Central  Google Scholar 

  75. Berman DM, Willman MA, Han D, Kleiner G, Kenyon NM, Cabrera O, Karl JA, Wiseman RW, O’Connor DH, Bartholomew AM, Kenyon NS (2010) Mesenchymal stem cells enhance allogeneic islet engraftment in nonhuman primates. Diabetes 59:2558–2568. https://doi.org/10.2337/db10-0136

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Tang YY, Zhou Y, Li HJ (2021) Advances in mesenchymal stem cell exosomes: a review. Stem Cell Res Ther. https://doi.org/10.1186/s13287-021-02138-7

    Article  PubMed  PubMed Central  Google Scholar 

  77. Margiana R, Markov A, Zekiy AO, Hamza MU, Al-Dabbagh KA, Al-Zubaidi SH, Hameed NM, Ahmad I, Sivaraman R, Kzar HH, Al-Gazally ME, Mustafa YF, Siahmansouri H (2022) Clinical application of mesenchymal stem cell in regenerative medicine: a narrative review. Stem Cell Res Ther. https://doi.org/10.1186/s13287-022-03054-0

    Article  PubMed  PubMed Central  Google Scholar 

  78. Kadam S, Muthyala S, Nair P, Bhonde R (2010) Human placenta-derived mesenchymal stem cells and islet-like cell clusters generated from these cells as a novel source for stem cell therapy in diabetes. Rev Diabet Stud 7:168–182. https://doi.org/10.1900/rds.2010.7.168

    Article  PubMed  PubMed Central  Google Scholar 

  79. Zhang Y, Shen W, Hua J, Lei A, Lv C, Wang H, Yang C, Gao Z, Dou Z (2010) Pancreatic islet-like clusters from bone marrow mesenchymal stem cells of human first-trimester abortus can cure streptozocin-induced mouse diabetes. Rejuvenation Res 13:695–706. https://doi.org/10.1089/rej.2009.1016

    Article  CAS  PubMed  Google Scholar 

  80. Path G, Perakakis N, Mantzoros CS, Seufert J (2019) Stem cells in the treatment of diabetes mellitus - Focus on mesenchymal stem cells. Metabolism 90:1–15. https://doi.org/10.1016/j.metabol.2018.10.005

    Article  CAS  PubMed  Google Scholar 

  81. Eydian Z, Mohammad Ghasemi A, Ansari S, Kamali AN, Khosravi M, Momtaz S, Riki S, Rafighdoost L, Entezari Heravi R (2022) Differentiation of multipotent stem cells to insulin-producing cells for treatment of diabetes mellitus: bone marrow- and adipose tissue-derived cells comparison. Mol Biol Rep 49:3539–3548. https://doi.org/10.1007/s11033-022-07194-7

    Article  CAS  PubMed  Google Scholar 

  82. Cho J, D’Antuono M, Glicksman M, Wang J, Jonklaas J (2018) A review of clinical trials: mesenchymal stem cell transplant therapy in type 1 and type 2 diabetes mellitus. Am J Stem Cells 7:82–93

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Millman JR, Xie C, Van Dervort A, Gürtler M, Pagliuca FW, Melton DA (2016) Generation of stem cell-derived β-cells from patients with type 1 diabetes. Nat Commun 7:11463. https://doi.org/10.1038/ncomms11463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Leite NC, Sintov E, Meissner TB, Brehm MA, Greiner DL, Harlan DM, Melton DA (2020) Modeling type 1 diabetes in vitro using human pluripotent stem cells. Cell Rep 32:107894. https://doi.org/10.1016/j.celrep.2020.107894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Shojima N, Yamauchi T (2023) Progress in genetics of type 2 diabetes and diabetic complications. J Diabetes Investig 14:503–515. https://doi.org/10.1111/jdi.13970

    Article  PubMed  PubMed Central  Google Scholar 

  86. Zeng H, Guo M, Zhou T, Tan L, Chong CN, Zhang T, Dong X, Xiang JZ, Yu AS, Yue L, Qi Q, Evans T, Graumann J, Chen S (2016) An isogenic human ESC platform for functional evaluation of genome-wide-association-study-identified diabetes genes and drug discovery. Cell Stem Cell 19:326–340. https://doi.org/10.1016/j.stem.2016.07.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Wen XJ, Yang YS (2017) Emerging roles of GLIS3 in neonatal diabetes, type 1 and type 2 diabetes. J Mol Endocrinol 58:R73–R85. https://doi.org/10.1530/Jme-16-0232

    Article  CAS  PubMed  Google Scholar 

  88. Amin S, Cook B, Zhou T, Ghazizadeh Z, Lis R, Zhang T, Khalaj M, Crespo M, Perera M, Xiang JZ, Zhu Z, Tomishima M, Liu C, Naji A, Evans T, Huangfu D, Chen S (2018) Discovery of a drug candidate for GLIS3-associated diabetes. Nat Commun 9:2681. https://doi.org/10.1038/s41467-018-04918-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Hussain MA, Akalestou E, Song WJ (2016) Inter-organ communication and regulation of beta cell function. Diabetologia 59:659–667. https://doi.org/10.1007/s00125-015-3862-7

    Article  PubMed  PubMed Central  Google Scholar 

  90. Picollet-D’hahan N, Zuchowska A, Lemeunier I, Le Gac S (2021) Multiorgan-on-a-Chip: a systemic approach to model and decipher inter-organ communication. Trends Biotechnol 39:788–810. https://doi.org/10.1016/j.tibtech.2020.11.014

    Article  CAS  PubMed  Google Scholar 

  91. Bauer S, Wennberg Huldt C, Kanebratt KP, Durieux I, Gunne D, Andersson S, Ewart L, Haynes WG, Maschmeyer I, Winter A, Ämmälä C, Marx U, Andersson TB (2017) Functional coupling of human pancreatic islets and liver spheroids on-a-chip: towards a novel human ex vivo type 2 diabetes model. Sci Rep 7:14620. https://doi.org/10.1038/s41598-017-14815-w

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Yamashita-Sugahara Y, Matsumoto M, Ohtaka M, Nishimura K, Nakanishi M, Mitani K, Okazaki Y (2016) An inhibitor of fibroblast growth factor receptor-1 (FGFR1) promotes late-stage terminal differentiation from NGN3+ pancreatic endocrine progenitors. Sci Rep 6:35908. https://doi.org/10.1038/srep35908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kimura A, Toyoda T, Nishi Y, Nasu M, Ohta A, Osafune K (2017) Small molecule AT7867 proliferates PDX1-expressing pancreatic progenitor cells derived from human pluripotent stem cells. Stem Cell Res 24:61–68. https://doi.org/10.1016/j.scr.2017.08.010

    Article  CAS  PubMed  Google Scholar 

  94. Korostylev A, Mahaddalkar PU, Keminer O, Hadian K, Schorpp K, Gribbon P, Lickert H (2017) A high-content small molecule screen identifies novel inducers of definitive endoderm. Mol Metab 6:640–650. https://doi.org/10.1016/j.molmet.2017.04.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhou T, Kim TW, Chong CN, Tan L, Amin S, Badieyan ZS, Mukherjee S, Ghazizadeh Z, Zeng H, Guo M, Crespo M, Zhang T, Kenyon R, Robinson CL, Apostolou E, Wang H, Xiang JZ, Evans T, Studer L, Chen SB (2018) A hPSC-based platform to discover gene-environment interactions that impact human β-cell and dopamine neuron survival. Nat Commun. https://doi.org/10.1038/s41467-018-07201-1

    Article  PubMed  PubMed Central  Google Scholar 

  96. Wei Z, Yoshihara E, He N, Hah N, Fan W, Pinto AFM, Huddy T, Wang Y, Ross B, Estepa G, Dai Y, Ding N, Sherman MH, Fang S, Zhao X, Liddle C, Atkins AR, Yu RT, Downes M, Evans RM (2018) Vitamin D switches BAF complexes to protect β cells. Cell 173:1135-1149.e15. https://doi.org/10.1016/j.cell.2018.04.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Bashor CJ, Hilton IB, Bandukwala H, Smith DM, Veiseh O (2022) Engineering the next generation of cell-based therapeutics. Nat Rev Drug Discov 21:655–675. https://doi.org/10.1038/s41573-022-00476-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Wang X, Gao M, Wang Y, Zhang Y (2022) The progress of pluripotent stem cell-derived pancreatic β-cells regeneration for diabetic therapy. Front Endocrinol (Lausanne) 13:927324. https://doi.org/10.3389/fendo.2022.927324

    Article  PubMed  Google Scholar 

  99. Ramzy A, Thompson DM, Ward-Hartstonge KA, Ivison S, Cook L, Garcia RV, Loyal J, Kim PTW, Warnock GL, Levings MK, Kieffer TJ (2021) Implanted pluripotent stem-cell-derived pancreatic endoderm cells secrete glucose-responsive C-peptide in patients with type 1 diabetes. Cell Stem Cell 28:2047-2061.e5. https://doi.org/10.1016/j.stem.2021.10.003

    Article  CAS  PubMed  Google Scholar 

  100. Shapiro AMJ, Thompson D, Donner TW, Bellin MD, Hsueh W, Pettus J, Wilensky J, Daniels M, Wang RM, Brandon EP, Jaiman MS, Kroon EJ, D’Amour KA, Foyt HL (2021) Insulin expression and C-peptide in type 1 diabetes subjects implanted with stem cell-derived pancreatic endoderm cells in an encapsulation device. Cell Rep Med. https://doi.org/10.1016/j.xcrm.2021.100466

    Article  PubMed  PubMed Central  Google Scholar 

  101. Russ HA, Parent AV, Ringler JJ, Hennings TG, Nair GG, Shveygert M, Guo T, Puri S, Haataja L, Cirulli V, Blelloch R, Szot GL, Arvan P, Hebrok M (2015) Controlled induction of human pancreatic progenitors produces functional beta-like cells in vitro. EMBO J 34:1759–1772. https://doi.org/10.15252/embj.201591058

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Agulnick AD, Ambruzs DM, Moorman MA, Bhoumik A, Cesario RM, Payne JK, Kelly JR, Haakmeester C, Srijemac R, Wilson AZ, Kerr J, Frazier MA, Kroon EJ, D’Amour KA (2015) Insulin-producing endocrine cells differentiated in vitro from human embryonic stem cells function in macroencapsulation devices in vivo. Stem Cells Transl Med 4:1214–1222. https://doi.org/10.5966/sctm.2015-0079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Nostro MC, Sarangi F, Yang C, Holland A, Elefanty AG, Stanley EG, Greiner DL, Keller G (2015) Efficient generation of NKX6-1+ pancreatic progenitors from multiple human pluripotent stem cell lines. Stem Cell Rep 4:591–604. https://doi.org/10.1016/j.stemcr.2015.02.017

    Article  CAS  Google Scholar 

  104. Memon B, Karam M, Al-Khawaga S, Abdelalim EM (2018) Enhanced differentiation of human pluripotent stem cells into pancreatic progenitors co-expressing PDX1 and NKX6.1. Stem Cell Res Ther 9:15. https://doi.org/10.1186/s13287-017-0759-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Desai T, Shea LD (2017) Advances in islet encapsulation technologies. Nat Rev Drug Discov 16:338–350. https://doi.org/10.1038/nrd.2016.232

    Article  CAS  PubMed  Google Scholar 

  106. Wu S, Wang L, Fang Y, Huang H, You X, Wu J (2021) Advances in encapsulation and delivery strategies for islet transplantation. Adv Healthc Mater 10:e2100965. https://doi.org/10.1002/adhm.202100965

    Article  CAS  PubMed  Google Scholar 

  107. Vaithilingam V, Bal S, Tuch BE (2017) Encapsulated islet transplantation: where do we stand? Rev Diabet Stud 14:51–78. https://doi.org/10.1900/rds.2017.14.51

    Article  PubMed  PubMed Central  Google Scholar 

  108. Rafael E, Wernerson A, Arner P, Wu GS, Tibell A (1999) In vivo evaluation of glucose permeability of an immunoisolation device intended for islet transplantation: a novel application of the microdialysis technique. Cell Transplant 8:317–326. https://doi.org/10.1177/096368979900800302

    Article  CAS  PubMed  Google Scholar 

  109. Motté E, Szepessy E, Suenens K, Stangé G, Bomans M, Jacobs-Tulleneers-Thevissen D, Ling Z, Kroon E, Pipeleers D (2014) Composition and function of macroencapsulated human embryonic stem cell-derived implants: comparison with clinical human islet cell grafts. Am J Physiol Endocrinol Metab 307:E838–E846. https://doi.org/10.1152/ajpendo.00219.2014

    Article  CAS  PubMed  Google Scholar 

  110. Robert T, De Mesmaeker I, Stangé GM, Suenens KG, Ling Z, Kroon EJ, Pipeleers DG (2018) Functional beta cell mass from device-encapsulated HESC-derived pancreatic endoderm achieving metabolic control. Stem Cell Rep 10:739–750. https://doi.org/10.1016/j.stemcr.2018.01.040

    Article  CAS  Google Scholar 

  111. Bruin JE, Rezania A, Xu J, Narayan K, Fox JK, O’Neil JJ, Kieffer TJ (2013) Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice. Diabetologia 56:1987–1998. https://doi.org/10.1007/s00125-013-2955-4

    Article  PubMed  Google Scholar 

  112. Zhang Q, Gonelle-Gispert C, Li Y, Geng Z, Gerber-Lemaire S, Wang Y, Buhler L (2022) Islet encapsulation: new developments for the treatment of type 1 diabetes. Front Immunol 13:869984. https://doi.org/10.3389/fimmu.2022.869984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Samojlik MM, Stabler CL (2021) Designing biomaterials for the modulation of allogeneic and autoimmune responses to cellular implants in type 1 diabetes. Acta Biomater 133:87–101. https://doi.org/10.1016/j.actbio.2021.05.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Teramura Y, Iwata H (2009) Islet encapsulation with living cells for improvement of biocompatibility. Biomaterials 30:2270–2275. https://doi.org/10.1016/j.biomaterials.2009.01.036

    Article  CAS  PubMed  Google Scholar 

  115. Cui W, Khan KM, Ma X, Chen G, Desai CS (2020) Human amniotic epithelial cells and human amniotic membrane as a vehicle for islet cell transplantation. Trans Proc 52:982–986. https://doi.org/10.1016/j.transproceed.2020.01.022

    Article  CAS  Google Scholar 

  116. Sabek OM, Ferrati S, Fraga DW, Sih J, Zabre EV, Fine DH, Ferrari M, Gaber AO, Grattoni A (2013) Characterization of a nanogland for the autotransplantation of human pancreatic islets. Lab Chip 13:3675–3688. https://doi.org/10.1039/c3lc50601k

    Article  CAS  PubMed  Google Scholar 

  117. Barra JM, Kozlovskaya V, Burnette KS, Banerjee RR, Fraker CA, Kharlampieva E, Tse HM (2023) Localized cytotoxic T cell-associated antigen 4 and antioxidant islet encapsulation alters macrophage signaling and induces regulatory and anergic T cells to enhance allograft survival. Am J Trans 23:498–511. https://doi.org/10.1016/j.ajt.2023.01.007

    Article  Google Scholar 

  118. Elisseeff J, Badylak SF, Boeke JD (2021) Immune and genome engineering as the future of transplantable tissue. N Engl J Med 385:2451–2462. https://doi.org/10.1056/NEJMra1913421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Ghoneim MA, Gabr MM, El-Halawani SM, Refaie AF (2024) Current status of stem cell therapy for type 1 diabetes: a critique and a prospective consideration. Stem Cell Res Ther 15:23. https://doi.org/10.1186/s13287-024-03636-0

    Article  PubMed  PubMed Central  Google Scholar 

  120. Deuse T, Hu X, Gravina A, Wang D, Tediashvili G, De C, Thayer WO, Wahl A, Garcia JV, Reichenspurner H, Davis MM, Lanier LL, Schrepfer S (2019) Hypoimmunogenic derivatives of induced pluripotent stem cells evade immune rejection in fully immunocompetent allogeneic recipients. Nat Biotechnol 37:252–258. https://doi.org/10.1038/s41587-019-0016-3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Han X, Wang M, Duan S, Franco PJ, Kenty JH, Hedrick P, Xia Y, Allen A, Ferreira LMR, Strominger JL, Melton DA, Meissner TB, Cowan CA (2019) Generation of hypoimmunogenic human pluripotent stem cells. Proc Natl Acad Sci U S A 116:10441–10446. https://doi.org/10.1073/pnas.1902566116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Gerace D, Zhou Q, Kenty JH, Veres A, Sintov E, Wang X, Boulanger KR, Li H, Melton DA (2023) Engineering human stem cell-derived islets to evade immune rejection and promote localized immune tolerance. Cell Rep Med 4:100879. https://doi.org/10.1016/j.xcrm.2022.100879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Santini-Gonzalez J, Castro-Gutierrez R, Becker MW, Rancourt C, Russ HA, Phelps EA (2022) Human stem cell derived beta-like cells engineered to present PD-L1 improve transplant survival in NOD mice carrying human HLA class I. Front Endocrinol (Lausanne) 13:989815. https://doi.org/10.3389/fendo.2022.989815

    Article  PubMed  Google Scholar 

  124. Hu X, Gattis C, Olroyd AG, Friera AM, White K, Young C, Basco R, Lamba M, Wells F, Ankala R, Dowdle WE, Lin A, Egenberger K, Rukstalis JM, Millman JR, Connolly AJ, Deuse T, Schrepfer S (2023) Human hypoimmune primary pancreatic islets avoid rejection and autoimmunity and alleviate diabetes in allogeneic humanized mice. Sci Transl Med 15:eadg5794. https://doi.org/10.1126/scitranslmed.adg5794

    Article  CAS  PubMed  Google Scholar 

  125. Hu X, White K, Olroyd AG, DeJesus R, Dominguez AA, Dowdle WE, Friera AM, Young C, Wells F, Chu EY, Ito CE, Krishnapura H, Jain S, Ankala R, McGill TJ, Lin A, Egenberger K, Gagnon A, Michael Rukstalis J, Hogrebe NJ, Gattis C, Basco R, Millman JR, Kievit P, Davis MM, Lanier LL, Connolly AJ, Deuse T, Schrepfer S (2024) Hypoimmune induced pluripotent stem cells survive long term in fully immunocompetent, allogeneic rhesus macaques. Nat Biotechnol 42:413–423. https://doi.org/10.1038/s41587-023-01784-x

    Article  CAS  PubMed  Google Scholar 

  126. Bergström M, Yao M, Müller M, Korsgren O, von Zur-Mühlen B, Lundgren T (2021) Autologous regulatory T cells in clinical intraportal allogenic pancreatic islet transplantation. Transpl Int 34:2816–2823. https://doi.org/10.1111/tri.14163

    Article  CAS  PubMed  Google Scholar 

  127. Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ (2019) An anti-CD3 antibody, Teplizumab, in relatives at risk for type 1 diabetes. N Engl J Med 381:603–613. https://doi.org/10.1056/NEJMoa1902226

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Merani S, Toso C, Emamaullee J, Shapiro AM (2008) Optimal implantation site for pancreatic islet transplantation. Br J Surg 95:1449–1461. https://doi.org/10.1002/bjs.6391

    Article  CAS  PubMed  Google Scholar 

  129. Addison P, Fatakhova K, Rodriguez Rilo HL (2020) Considerations for an alternative site of islet cell transplantation. J Diabetes Sci Technol 14:338–344. https://doi.org/10.1177/1932296819868495

    Article  PubMed  Google Scholar 

  130. Inagaki A, Imura T, Nakamura Y, Ohashi K, Goto M (2021) The liver surface is an attractive transplant site for pancreatic islet transplantation. J Clin Med. https://doi.org/10.3390/jcm10040724

    Article  PubMed  PubMed Central  Google Scholar 

  131. Pepper AR, Gala-Lopez B, Pawlick R, Merani S, Kin T, Shapiro AM (2015) A prevascularized subcutaneous device-less site for islet and cellular transplantation. Nat Biotechnol 33:518–523. https://doi.org/10.1038/nbt.3211

    Article  CAS  PubMed  Google Scholar 

  132. Kinney SM, Ortaleza K, Vlahos AE, Sefton MV (2022) Degradable methacrylic acid-based synthetic hydrogel for subcutaneous islet transplantation. Biomaterials 281:121342. https://doi.org/10.1016/j.biomaterials.2021.121342

    Article  CAS  PubMed  Google Scholar 

  133. Pellicciaro M, Vella I, Lanzoni G, Tisone G, Ricordi C (2017) The greater omentum as a site for pancreatic islet transplantation. CellR4 Repair Replace Regen Reprogram 5:e2410

    PubMed  PubMed Central  Google Scholar 

  134. Damyar K, Farahmand V, Whaley D, Alexander M, Lakey JRT (2021) An overview of current advancements in pancreatic islet transplantation into the omentum. Islets 13:115–120. https://doi.org/10.1080/19382014.2021.1954459

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Yasunami Y, Lacy PE, Finke EH (1983) A new site for islet transplantation–a peritoneal-omental pouch. Transplantation 36:181–182. https://doi.org/10.1097/00007890-198308000-00014

    Article  CAS  PubMed  Google Scholar 

  136. Ao ZL, Matayoshi K, Lakey JRT, Rajotte RV, Warnock GL (1993) Survival and function of purified islets in the omental pouch site of outbred dogs. Transplantation 56:524–529. https://doi.org/10.1097/00007890-199309000-00007

    Article  CAS  PubMed  Google Scholar 

  137. Deng H, Zhang A, Pang DRR, Xi Y, Yang Z, Matheson R, Li G, Luo H, Lee KM, Fu Q, Zou Z, Chen T, Wang Z, Rosales IA, Peters CW, Yang J, Coronel MM, Yolcu ES, Shirwan H, García AJ, Markmann JF, Lei J (2023) Bioengineered omental transplant site promotes pancreatic islet allografts survival in non-human primates. Cell Rep Med 4:100959. https://doi.org/10.1016/j.xcrm.2023.100959

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Schwarzer A, Talbot SR, Selich A, Morgan M, Schott JW, Dittrich-Breiholz O, Bastone AL, Weigel B, Ha TC, Dziadek V, Gijsbers R, Thrasher AJ, Staal FJT, Gaspar HB, Modlich U, Schambach A, Rothe M (2021) Predicting genotoxicity of viral vectors for stem cell gene therapy using gene expression-based machine learning. Mol Ther 29:3383–3397. https://doi.org/10.1016/j.ymthe.2021.06.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Hentze H, Soong PL, Wang ST, Phillips BW, Putti TC, Dunn NR (2009) Teratoma formation by human embryonic stem cells: Evaluation of essential parameters for future safety studies. Stem Cell Res 2:198–210. https://doi.org/10.1016/j.scr.2009.02.002

    Article  PubMed  Google Scholar 

  140. Pellegrini S, Zamarian V, Sordi V (2022) Strategies to improve the safety of iPSC-derived β cells for β cell replacement in diabetes. Trans Int. https://doi.org/10.3389/ti.2022.10575

    Article  Google Scholar 

  141. Jiang W, Sui X, Zhang DH, Liu M, Ding MX, Shi Y, Deng HK (2011) CD24: a novel surface marker for PDX1-positive pancreatic progenitors derived from human embryonic stem cells. Stem Cells 29:609–617. https://doi.org/10.1002/stem.608

    Article  CAS  PubMed  Google Scholar 

  142. Ameri J, Borup R, Prawiro C, Ramond C, Schachter KA, Scharfmann R, Semb H (2017) Efficient generation of glucose-responsive beta cells from isolated GP2 human pancreatic progenitors. Cell Rep 19:36–49. https://doi.org/10.1016/j.celrep.2017.03.032

    Article  CAS  PubMed  Google Scholar 

  143. Cogger KF, Sinha A, Sarangi F, McGaugh EC, Saunders D, Dorrell C, Mejia-Guerrero S, Aghazadeh Y, Rourke JL, Screaton RA, Grompe M, Streeter PR, Powers AC, Brissova M, Kislinger T, Nostro MC (2017) Glycoprotein 2 is a specific cell surface marker of human pancreatic progenitors. Nat Commun. https://doi.org/10.1038/s41467-017-00561-0

    Article  PubMed  PubMed Central  Google Scholar 

  144. Mahaddalkar PU, Scheibner K, Pfluger S, Ansarullah SM, Beckenbauer J, Irmler M, Beckers J, Knöbel S, Lickert H (2020) Generation of pancreatic β cells from CD177 anterior definitive endoderm. Nat Biotechnol 38:1061. https://doi.org/10.1038/s41587-020-0492-5

    Article  CAS  PubMed  Google Scholar 

  145. Salinno C, Büttner M, Cota P, Tritschler S, Tarquis-Medina M, Bastidas-Ponce A, Scheibner K, Burtscher I, Böttcher A, Theis FJ, Bakhti M, Lickert H (2021) CD81 marks immature and dedifferentiated pancreatic β-cells. Mol Metab. https://doi.org/10.1016/j.molmet.2021.101188

    Article  PubMed  PubMed Central  Google Scholar 

  146. Tang C, Lee AS, Volkmer JP, Sahoo D, Nag D, Mosley AR, Inlay MA, Ardehali R, Chavez SL, Pera RR, Behr B, Wu JC, Weissman IL, Drukker M (2011) An antibody against SSEA-5 glycan on human pluripotent stem cells enables removal of teratoma-forming cells. Nat Biotechnol 29:829-U86. https://doi.org/10.1038/nbt.1947

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Pellegrini S, Zamarian V, Sordi V (2022) Strategies to improve the safety of iPSC-derived beta cells for beta cell replacement in diabetes. Transpl Int 35:10575. https://doi.org/10.3389/ti.2022.10575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Sheikh S, Ernst D, Keating A (2021) Prodrugs and prodrug-activated systems in gene therapy. Mol Ther 29:1716–1728. https://doi.org/10.1016/j.ymthe.2021.04.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  149. Nagashima T, Shimizu K, Matsumoto R, Honda H (2018) Selective elimination of human induced pluripotent stem cells using medium with high concentration of L-alanine. Sci Rep 8:12427. https://doi.org/10.1038/s41598-018-30936-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Qadir MMF, Alvarez-Cubela S, Belle K, Sapir T, Messaggio F, Johnson KB, Umland O, Hardin D, Klein D, Perez-Alvarez I, Sadiq F, Alcazar O, Inverardi LA, Ricordi C, Buchwald P, Fraker CA, Pastori RL, Dominguez-Bendala J (2019) A double fail-safe approach to prevent tumorigenesis and select pancreatic beta cells from human embryonic stem cells. Stem Cell Reports 12:611–623. https://doi.org/10.1016/j.stemcr.2019.01.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Di Stasi A, Tey SK, Dotti G, Fujita Y, Kennedy-Nasser A, Martinez C, Straathof K, Liu E, Durett AG, Grilley B, Liu H, Cruz CR, Savoldo B, Gee AP, Schindler J, Krance RA, Heslop HE, Spencer DM, Rooney CM, Brenner MK (2011) Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med 365:1673–1683. https://doi.org/10.1056/NEJMoa1106152

    Article  PubMed  PubMed Central  Google Scholar 

  152. Liu Y, Yang Y, Suo Y, Li C, Chen M, Zheng S, Li H, Tang C, Fan N, Lan T, Zhou J, Li Y, Wang J, Chen H, Zou Q, Lai L (2022) Inducible caspase-9 suicide gene under control of endogenous oct4 to safeguard mouse and human pluripotent stem cell therapy. Mol Ther Methods Clin Dev 24:332–341. https://doi.org/10.1016/j.omtm.2022.01.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Yagyu S, Hoyos V, Del Bufalo F, Brenner MK (2015) An suicide gene to improve the safety of therapy using human induced pluripotent stem cells. Mol Ther 23:1475–1485. https://doi.org/10.1038/mt.2015.100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Shi ZD, Tchao J, Wu L, Carman AJ (2020) Precision installation of a highly efficient suicide gene safety switch in human induced pluripotent stem cells. Stem Cells Transl Med 9:1378–1388. https://doi.org/10.1002/sctm.20-0007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This study was supported by the National Natural Science Foundation of China (No. 82270846).

Author information

Authors and Affiliations

  1. Molecular Medicine Research Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 1 Keyuan 4th Road, Gaopeng Street, Chengdu, 610041, China

    Xingrong Feng, Hongmei Zhang, Shanshan Yang, Daxin Cui, Yanting Wu, Xiaocun Qi & Zhiguang Su

Authors
  1. Xingrong Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongmei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shanshan Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Daxin Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yanting Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Xiaocun Qi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhiguang Su
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

XRF, HMZ, SSY, DXC, YTW, XCQ and ZGS conceptualization. XRF and ZGS: writing original draft and editing. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Zhiguang Su.

Ethics declarations

Conflict of interest

The authors declare no conflict interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Feng, X., Zhang, H., Yang, S. et al. From stem cells to pancreatic β-cells: strategies, applications, and potential treatments for diabetes. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-024-04999-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s11010-024-04999-x

Keywords

Search

Navigation