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Publications

Journal Article Review Ppublish 17 citations

PubMed: 39227741 DOI: 10.1038/s41574-024-01029-0

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead.

Nat Rev Endocrinol 21(1):14-30

Authors: Alessandro Grattoni, Gregory Korbutt, Alice A Tomei, Andrés J García, Andrew R Pepper, Cherie Stabler, Michael Brehm, Klearchos Papas, Antonio Citro, Haval Shirwan, Jeffrey R Millman, Juan Melero-Martin, Melanie Graham, Michael Sefton, Minglin Ma, Norma Kenyon, Omid Veiseh, Tejal A Desai, M Cristina Nostro, Marjana Marinac, Megan Sykes, Holger A Russ, Jon Odorico, Qizhi Tang, Camillo Ricordi, Esther Latres, Nicholas E Mamrak, Jaime Giraldo, Mark C Poznansky, Paul de Vos

Affiliations

  • Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, USA.
  • Department of Surgery, Houston Methodist Hospital, Houston, TX, USA.
  • Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA.
  • Alberta Diabetes Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
  • Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Department of Biomedical Engineering, University of Miami, Miami, FL, USA.
  • Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA.
  • J. Crayton Pruitt Family Department of Biomedical Engineering, Herbert Wertheim College of Engineering, University of Florida, Gainesville, FL, USA.
  • Diabetes Institute, University of Florida, Gainesville, FL, USA.
  • Program in Molecular Medicine, Diabetes Center of Excellence, University of Massachusetts Chan Medical School, Worcester, MA, USA.
  • Department of Surgery, The University of Arizona, Tucson, AZ, USA.
  • Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
  • Department of Pediatrics, Ellis Fischel Cancer Center, School of Medicine, University of Missouri, Columbia, MO, USA.
  • Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO, USA.
  • Department of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
  • Department of Cardiac Surgery, Boston Children's Hospital, Boston, MA, USA.
  • Department of Surgery, Harvard Medical School, Boston, MA, USA.
  • Harvard Stem Cell Institute, Cambridge, MA, USA.
  • Department of Surgery, University of Minnesota, Minneapolis, MN, USA.
  • Department of Veterinary Population Medicine, University of Minnesota, St. Paul, MN, USA.
  • Institute of Biomedical Engineering, University of Toronto, Toronto, Ontario, Canada.
  • Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
  • Department of Biological and Environmental Engineering, Cornell University, Ithaca, NY, USA.
  • Department of Bioengineering, Rice University, Houston, TX, USA.
  • University of California, San Francisco, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA.
  • Brown University, School of Engineering, Providence, RI, USA.
  • McEwen Stem Cell Institute, University Health Network, Toronto, ON, Canada.
  • Department of Physiology, University of Toronto, Toronto, ON, Canada.
  • Advocacy Department, Breakthrough T1D, Washington, DC, USA.
  • Department of Medicine, Columbia Center for Translational Immunology, Columbia University, New York, NY, USA.
  • Department of Microbiology and Immunology, Columbia University, New York, NY, USA.
  • Department of Surgery, Columbia University, New York, NY, USA.
  • Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL, USA.
  • UW Health Transplant Center, Madison, WI, USA.
  • Division of Transplantation, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
  • Diabetes Center, University of California San Francisco, San Francisco, CA, USA.
  • Department of Surgery, University of California San Francisco, San Francisco, CA, US.
  • Gladstone Institute of Genomic Immunology, University of California San Francisco, San Francisco, CA, USA.
  • Research Department, Breakthrough T1D, New York, NY, USA.
  • Research Department, Breakthrough T1D, New York, NY, USA.
  • Vaccine and Immunotherapy Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
  • Immunoendocrinology, Division of Medical Biology, Department of Pathology and Medical Biology, University of Groningen and University Medical Center Groningen, Groningen, Netherlands.

Abstract

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.

MeSH

Diabetes Mellitus, Cells, Insulin, Therapeutics, Transplantation, Diabetes Mellitus, Type 1, Endocrine System Diseases

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