Allo Beta Cell transplantation: specific features, unanswered questions, and immunological challenge.

autoimmunity beta cell replacement immunomodulation immunosuppression islet transplant type 1 diabetes

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2023
Historique:
received: 17 10 2023
accepted: 06 11 2023
medline: 11 12 2023
pubmed: 11 12 2023
entrez: 11 12 2023
Statut: epublish

Résumé

Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.

Identifiants

pubmed: 38077372
doi: 10.3389/fimmu.2023.1323439
pmc: PMC10701551
doi:

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1323439

Informations de copyright

Copyright © 2023 Caldara, Tomajer, Monti, Sordi, Citro, Chimienti, Gremizzi, Catarinella, Tentori, Paloschi, Melzi, Mercalli, Nano, Magistretti, Partelli and Piemonti.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Rossana Caldara (R)

Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy.

Valentina Tomajer (V)

Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy.

Paolo Monti (P)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Valeria Sordi (V)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Antonio Citro (A)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Raniero Chimienti (R)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
Università Vita-Salute San Raffaele, Milan, Italy.

Chiara Gremizzi (C)

Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy.

Davide Catarinella (D)

Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy.

Stefano Tentori (S)

Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy.

Vera Paloschi (V)

Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy.

Raffella Melzi (R)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Alessia Mercalli (A)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Rita Nano (R)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Paola Magistretti (P)

Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.

Stefano Partelli (S)

Pancreatic Surgery, Pancreas Translational & Clinical Research Center, IRCCS Ospedale San Raffaele, Milan, Italy.
Università Vita-Salute San Raffaele, Milan, Italy.

Lorenzo Piemonti (L)

Clinic Unit of Regenerative Medicine and Organ Transplants, IRCCS Ospedale San Raffaele, Milan, Italy.
Diabetes Research Institute, IRCCS Ospedale San Raffaele, Milan, Italy.
Università Vita-Salute San Raffaele, Milan, Italy.

Classifications MeSH