TY - JOUR
T1 - Harnessing cellular therapeutics for type 1 diabetes mellitus
T2 - progress, challenges, and the road ahead
AU - Grattoni, Alessandro
AU - Korbutt, Gregory
AU - Tomei, Alice A.
AU - García, Andrés J.
AU - Pepper, Andrew R.
AU - Stabler, Cherie
AU - Brehm, Michael
AU - Papas, Klearchos
AU - Citro, Antonio
AU - Shirwan, Haval
AU - Millman, Jeffrey R.
AU - Melero-Martin, Juan
AU - Graham, Melanie
AU - Sefton, Michael
AU - Ma, Minglin
AU - Kenyon, Norma
AU - Veiseh, Omid
AU - Desai, Tejal A.
AU - Nostro, M. Cristina
AU - Marinac, Marjana
AU - Sykes, Megan
AU - Russ, Holger A.
AU - Odorico, Jon
AU - Tang, Qizhi
AU - Ricordi, Camillo
AU - Latres, Esther
AU - Mamrak, Nicholas E.
AU - Giraldo, Jaime
AU - Poznansky, Mark C.
AU - de Vos, Paul
N1 - Publisher Copyright:
© Springer Nature Limited 2024.
PY - 2025/1
Y1 - 2025/1
N2 - Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable β cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.
AB - Type 1 diabetes mellitus (T1DM) is a growing global health concern that affects approximately 8.5 million individuals worldwide. T1DM is characterized by an autoimmune destruction of pancreatic β cells, leading to a disruption in glucose homeostasis. Therapeutic intervention for T1DM requires a complex regimen of glycaemic monitoring and the administration of exogenous insulin to regulate blood glucose levels. Advances in continuous glucose monitoring and algorithm-driven insulin delivery devices have improved the quality of life of patients. Despite this, mimicking islet function and complex physiological feedback remains challenging. Pancreatic islet transplantation represents a potential functional cure for T1DM but is hindered by donor scarcity, variability in harvested cells, aggressive immunosuppressive regimens and suboptimal clinical outcomes. Current research is directed towards generating alternative cell sources, improving transplantation methods, and enhancing cell survival without chronic immunosuppression. This Review maps the progress in cell replacement therapies for T1DM and outlines the remaining challenges and future directions. We explore the state-of-the-art strategies for generating replenishable β cells, cell delivery technologies and local targeted immune modulation. Finally, we highlight relevant animal models and the regulatory aspects for advancing these technologies towards clinical deployment.
UR - http://www.scopus.com/inward/record.url?scp=85203014552&partnerID=8YFLogxK
U2 - 10.1038/s41574-024-01029-0
DO - 10.1038/s41574-024-01029-0
M3 - Review article
C2 - 39227741
AN - SCOPUS:85203014552
SN - 1759-5029
VL - 21
SP - 14
EP - 30
JO - Nature Reviews Endocrinology
JF - Nature Reviews Endocrinology
IS - 1
M1 - e158305
ER -