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

当前位置： X-MOL 学术 › Nat. Rev. Endocrinol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Harnessing cellular therapeutics for type 1 diabetes mellitus: progress, challenges, and the road ahead
Nature Reviews Endocrinology ( IF 31.0 ) Pub Date : 2024-09-03 , DOI: 10.1038/s41574-024-01029-0
Alessandro Grattoni _{1,

2,

3} , Gregory Korbutt _{4,

5} , Alice A Tomei _{6,

7,

8,

9} , Andrés J García ₁₀ , Andrew R Pepper ₅ , Cherie Stabler _{11,

12} , Michael Brehm ₁₃ , Klearchos Papas ₁₄ , Antonio Citro ₁₅ , Haval Shirwan ₁₆ , Jeffrey R Millman _{17,

18} , Juan Melero-Martin _{19,

20,

21} , Melanie Graham _{22,

23} , Michael Sefton _{24,

25} , Minglin Ma ₂₆ , Norma Kenyon _{6,

8} , Omid Veiseh ₂₇ , Tejal A Desai _{28,

29} , M Cristina Nostro _{30,

31} , Marjana Marinac ₃₂ , Megan Sykes _{33,

34,

35} , Holger A Russ _{12,

36} , Jon Odorico _{37,

38} , Qizhi Tang _{39,

40,

41} , Camillo Ricordi _{6,

8} , Esther Latres ₄₂ , Nicholas E Mamrak ₄₂ , Jaime Giraldo ₄₂ , Mark C Poznansky ₄₃ , Paul de Vos ₄₄

Affiliation

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.
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.

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.

中文翻译：

利用细胞疗法治疗 1 型糖尿病：进展、挑战和未来之路

1 型糖尿病（T1DM）是一个日益严重的全球健康问题，影响着全球约 850 万人。T1DM 的特征是胰腺 β 细胞的自身免疫性破坏，导致葡萄糖稳态中断。T1DM 的治疗干预需要一个复杂的血糖监测方案和外源性胰岛素给药以调节血糖水平。连续血糖监测和算法驱动的胰岛素输送装置的进步改善了患者的生活质量。尽管如此，模拟胰岛功能和复杂的生理反馈仍然具有挑战性。胰岛移植是 T1DM 的潜在功能性治愈方法，但受到供体稀缺、收获细胞的可变性、侵袭性免疫抑制方案和次优临床结果的阻碍。目前的研究旨在产生替代细胞来源、改进移植方法和在没有慢性免疫抑制的情况下提高细胞存活率。本综述描绘了 T1DM 细胞替代疗法的进展，并概述了仍然存在的挑战和未来方向。我们探索了产生可补充β细胞、细胞递送技术和局部靶向免疫调节的最新策略。最后，我们重点介绍了相关的动物模型和推动这些技术走向临床部署的监管方面。

更新日期：2024-09-03

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南