Optimizing Generation of Stem Cell-Derived Islet Cells

Verhoeff, Kevin; Cuesta-Gomez, Nerea; Jasra, Ila Tewari; Marfil‐Garza, Braulio A.; Dadheech, Nidheesh; Shapiro, A. M. James

doi:10.1007/s12015-022-10391-3

Cited by 11 publications

(11 citation statements)

References 148 publications

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“…From an authorial standpoint, Shapiro, Ricordi, and Matsumoto stand out as prolific contributors. Shapiro has published 126 papers, including 5 that explored the role of stem cells in IT, [35][36][37][38][39] one of these articles talks about the side effects and risks of islet transplants. [40] Ricordi, author of 121 papers, has affirmed in 1 article that the greater omentum can be used as a site for IT.…”

Section: General Informationmentioning

confidence: 99%

Global scientific trends on the islet transplantation in the 21st century: A bibliometric and visualized analysis

Chen,

Wu,

Zhang

et al. 2024

Medicine

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Background: Islet transplantation (IT) has emerged as a significant research area for the treatment of diabetes mellitus and has witnessed a surge in scholarly attention. Despite its growing importance, there is a lack of bibliometric analyses that encapsulate the evolution and scientific underpinnings of this field. This study aims to fill this gap by conducting a comprehensive bibliometric analysis to delineate current research hotspots and forecast future trajectories within the IT domain with a particular focus on evidence-based medicine practices. Methods: This analysis scrutinized literature from January 1, 2000, to October 1, 2023, using the Web of Science Core Collection (WoSCC). Employing bibliometric tools such as VOSviewer, CiteSpace, and the R package “bibliometrix,” we systematically evaluated the literature to uncover scientific trends and collaboration networks in IT research. Results: The analysis revealed 8388 publications from 82 countries, predominantly the United States and China. However, global cross-institutional collaboration in IT research requires further strengthening. The number of IT-related publications has increased annually. Leading research institutions in this field include Harvard University, the University of Alberta, the University of Miami, and the University of Minnesota. “Transplantation” emerges as the most frequently cited journal in this area. Shapiro and Ricordi were the most prolific authors, with 126 and 121 publications, respectively. Shapiro also led to co-citations, totaling 4808. Key research focuses on IT sites and procedures as well as novel therapies in IT. Emerging research hotspots are identified by terms like “xenotransplantation,” “apoptosis,” “stem cells,” “immunosuppression,” and “microencapsulation.” Conclusions: The findings underscore a mounting anticipation for future IT research, which is expected to delve deeper into evidence-based methodologies for IT sites, procedures, and novel therapeutic interventions. This shift toward evidence-based medicine underscores the field’s commitment to enhancing the efficacy and safety of IT for diabetes treatment, signaling a promising direction for future investigations aimed at optimizing patient outcomes.

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Section: General Informationmentioning

confidence: 99%

Global scientific trends on the islet transplantation in the 21st century: A bibliometric and visualized analysis

Chen,

Wu,

Zhang

et al. 2024

Medicine

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“…In fact, the clinical trial results of stem cell therapies for T1D are largely dissatisfactory [ 72 ], and many questions and technical hurdles still need to be solved. The major points that researchers should overcome include: (i) how to generate more mature functional beta cells in vitro from hPSCs; (ii) how to improve the differentiation efficiency of IPCs from hPSCs; (iii) how to protect implanted IPCs from autoimmune attack; (iv) how to generate enough desired cell types for clinical transplantation and (v) how to establish thorough insulin independence [ 73 , 74 ].…”

Section: Cell Therapy and The Organoid Perspectivementioning

confidence: 99%

“…However, methods to generate cells that meet quality and safety standards for clinical applications have been recently addressed [ 74 ], despite they are still far from application in clinical setting.…”

Section: Cell Therapy and The Organoid Perspectivementioning

confidence: 99%

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy

Noce

Nicoletti

Papaccio

et al. 2022

Cells

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Type 1 diabetes (T1D) is an autoimmune disease with immune cells’ islet infiltration (called “insulitis”), which leads to beta cell loss. Despite being the critical element of T1D occurrence and pathogenesis, insulitis is often present in a limited percentage of islets, also at diagnosis. Therefore, it is needed to define reproducible methods to detect insulitis and beta-cell decline, to allow accurate and early diagnosis and to monitor therapy. However, this goal is still far due to the morphological aspect of islet microvasculature, which is rather dense and rich, and is considerably rearranged during insulitis. More studies on microvasculature are required to understand if contrast-enhanced ultrasound sonography measurements of pancreatic blood-flow dynamics may provide a clinically deployable predictive marker to predict disease progression and therapeutic reversal in pre-symptomatic T1D patients. Therefore, it is needed to clarify the relation between insulitis and the dynamics of β cell loss and with coexisting mechanisms of dysfunction, according to clinical stage, as well as the micro vessels’ dynamics and microvasculature reorganization. Moreover, the ideal cell-based therapy of T1D should start from an early diagnosis allowing a sufficient isolation of specific Procr+ progenitors, followed by the generation and expansion of islet organoids, which could be transplanted coupled to an immune-regulatory therapy which will permit the maintenance of pancreatic islets and an effective and long-lasting insulitis reversal.

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“…This includes the use of innovative immunomodulatory drugs, tolerogenic immune cell therapies, and encapsulation to prevent physical contact between immune cells and transplanted cells, while allowing transport of nutrients and oxygen to and hormones from the cells [7][8][9] . There are also substantial efforts to develop islet-replacement strategies through use of pluripotent stem cell-derived insulin-producing cells 10,11 , which can be engineered to evade immune rejection and/or be combined with immunomodulatory therapies. The first clinical trials of genome-edited, pluripotent stem cell-derived insulin producing cells are underway (ClinicalTrials.gov Identifiers: NCT05210530; NCT04786262).…”

Section: Introductionmentioning

confidence: 99%

Human A2-CAR T cells reject HLA-A2+ human islets transplanted into mice without inducing graft versus host disease

Ellis

Mahdavi

Fung

et al. 2023

Preprint

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Background: Type 1 diabetes (T1D) is an autoimmune disease characterised by T cell mediated destruction of pancreatic beta-cells. Islet transplantation is an effective therapy, but its success is limited by islet quality and availability along with the need for immunosuppression. New approaches include use of stem cell-derived insulin-producing cells and immunomodulatory therapies, but a limitation is the paucity of reproducible animal models in which interactions between human immune cells and insulin-producing cells can be studied without the complication of xenogeneic graft-versus-host disease (xGVHD). Methods: We expressed an HLA-A2-specific chimeric antigen receptor (A2-CAR) in human CD4+ and CD8+ T cells and tested their ability to reject HLA-A2+ islets transplanted under the kidney capsule or anterior chamber of the eye of immunodeficient mice. T cell engraftment, islet function and xGVHD were assessed longitudinally. Results: The speed and consistency of A2-CAR T cells-mediated islet rejection varied depending on the number of A2-CAR T cells and the absence/presence of co-injected peripheral blood mononuclear cells (PBMCs). When <3 million A2-CAR T cells were injected, co-injection of PBMCs accelerated islet rejection but also induced xGVHD. In the absence of PBMCs, injection of 3 million A2-CAR T cells caused synchronous rejection of A2+ human islets within 1 week and without xGVHD for 12 weeks. Conclusions: Injection of A2-CAR T cells can be used to study rejection of human insulin-producing cells without the complication of xGVHD. The rapidity and synchrony of rejection will facilitate in vivo screening of new therapies designed to improve the success of islet-replacement therapies.

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Optimizing Generation of Stem Cell-Derived Islet Cells

Cited by 11 publications

References 148 publications

Global scientific trends on the islet transplantation in the 21st century: A bibliometric and visualized analysis

Global scientific trends on the islet transplantation in the 21st century: A bibliometric and visualized analysis

Insulitis in Human Type 1 Diabetic Pancreas: From Stem Cell Grafting to Islet Organoids for a Successful Cell-Based Therapy

Human A2-CAR T cells reject HLA-A2+ human islets transplanted into mice without inducing graft versus host disease

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