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Bioengineered Vascularized Insulin Producing Endocrine Tissues

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Pluripotent Stem Cell Therapy for Diabetes

Abstract

Islet transplantation is a promising treatment for type 1 diabetes (T1D), but limited islet engraftment hampers its success. In vivo, islets require time to remodel the hepatic parenchyma and establish their own microenvironment, but they face challenges such as ischemic reperfusion injury and immune reactions that hinder engraftment process. Bioengineering approaches are emerging as a solution to overcome these limitations. Specifically, ex vivo engineering of the islet niche microenvironment prior to implantation is gaining interest. These approaches aim to address challenges faced during isolation and in vivo engraftment, including the avascular phase, extracellular matrix (ECM) interactions, and mechanical/inflammatory stress. Alternative cell sources and native/synthetic materials are used to reshape the niche architecture, maximizing the cell-to-scaffold ratio. Meticulous design of the endocrine microenvironment, considering the endocrine, vasculature, and ECM compartments, has shown promise in improving engraftment and function. The generation of an endocrine vascularized pancreas platform enables ex vivo assembly of the essential building blocks, facilitating connection between the endocrine and vascular compartments. This approach has the potential to prevent inflammation, promote rapid vascularization, and enhance graft function. Here, we will discuss the up-to-date approaches in bioengineering the vascularized endocrine tissues based on reshaping all endocrine niche building blocks: ECM, vascular and endocrine compartments that are critical for successful assembly of an efficient vascularized endocrine insulin-producing tissue.

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Acknowledgments

FC and AN have contributed to the writing of the work in partial fulfillment of the requirements for obtaining the PhD degree at Vita-Salute San Raffaele University, Milano, Italy. CP has contributed to the writing and reviewing the manuscript. JB and EB have contributed to the writing of the manuscript. LP and AC have written and reviewed the manuscript and supervised the work. This work was supported by grants from the European Commission (Horizon 2020 Framework Program; VANGUARD grant 874700); Juvenile Diabetes Research Foundation (JDRF; grant 3-SRA-2022-1155-S-B); Fondazione Italiana Diabete (FID); “SOStegno 70 Insieme ai ragazzi diabetici Associazione Onlus” (project “Beta is better”), and fundraising campaign “Un brutto t1po”.

Author information

Author notes

  1. The authors Francesco Campo, Alessia Neroni and Cataldo Pignatelli have equally contributed to this work as first author

  2. The authors Ekaterine Berishvili, Lorenzo Piemonti, and Antonio Citro have equally contributed to this work as last author

Authors and Affiliations

  1. Diabetes Research Institute and Clinical Unit of Regenerative Medicine and Transplant, IRCCS San Raffaele Hospital, Milan, Italy

    Francesco Campo, Alessia Neroni, Cataldo Pignatelli, Lorenzo Piemonti & Antonio Citro

  2. University Vita-Salute San Raffaele, Milan, Italy

    Francesco Campo, Alessia Neroni & Lorenzo Piemonti

  3. Laboratory of Tissue Engineering and Organ Regeneration, Department of Surgery, University of Geneva, Geneva, Switzerland

    Juliette Bignard & Ekaterine Berishvili

  4. Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland

    Juliette Bignard & Ekaterine Berishvili

  5. Faculty Diabetes Center, University of Geneva Medical Center, Geneva, Switzerland

    Juliette Bignard & Ekaterine Berishvili

  6. School of Natural Sciences and Medicine, Ilia State University, Tbilisi, Georgia

    Ekaterine Berishvili

Authors
  1. Francesco Campo
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  2. Alessia Neroni
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  3. Cataldo Pignatelli
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  4. Juliette Bignard
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  5. Ekaterine Berishvili
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  6. Lorenzo Piemonti
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  7. Antonio Citro
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Corresponding authors

Correspondence to Ekaterine Berishvili , Lorenzo Piemonti or Antonio Citro .

Editor information

Editors and Affiliations

  1. Diabetes Research Institute and Clinical Unit of Regenerative Medicine and Transplant, IRCCS San Raffaele Hospital/Vita-Salute San Raffaele University, Milan, Italy

    Lorenzo Piemonti

  2. Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA

    Jon Odorico

  3. University of British Columbia, Vancouver, BC, Canada

    Timothy J . Kieffer

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

    Valeria Sordi

  5. Department of Medicine, Leiden University Medical Center, Leiden, The Netherlands

    Eelco de Koning

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Campo, F. et al. (2023). Bioengineered Vascularized Insulin Producing Endocrine Tissues. In: Piemonti, L., Odorico, J., Kieffer, T.J..., Sordi, V., de Koning, E. (eds) Pluripotent Stem Cell Therapy for Diabetes. Springer, Cham. https://doi.org/10.1007/978-3-031-41943-0_8

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