Applications of iPSC-derived beta cells from patients with diabetes

Maxwell, Kristina G.; Millman, Jeffrey R.

doi:10.1016/j.xcrm.2021.100238

Cited by 72 publications

(55 citation statements)

References 94 publications

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“…Human PSCs, including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), are considered desirable sources of islet lineage cells due to their virtually unlimited replicative capacity and the potential to produce almost all somatic cell types 65 . Extensive works have been focused on generating β cells from PSCs and many achievements have been made in the last decades, which were summarized by several reviews 66 - 71 . Therefore, many groups have utilized PSC-derived islet endocrine cells for making 3D human islet organoids.…”

Section: Cells For Making Human Islet Organoidsmentioning

confidence: 99%

Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies

Jiang¹,

Shen²,

Liu³

et al. 2022

Theranostics

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Diabetes is one of the most socially challenging health concerns. Even though islet transplantation has shown promise for insulin-dependent diabetes, there is still no effective method for curing diabetes due to the severe shortage of transplantable donors. In recent years, organoid technology has attracted lots of attention as organoid can mirror the human organ in vivo to the maximum extent in vitro, thus bridging the gap between cellular- and tissue/organ-level biological models. Concurrently, human pancreatic islet organoids are expected to be a considerable source of islet transplantation. To construct human islet-like organoids, the seeding cells, biomaterials and three-dimensional structure are three key elements. Herein, this review summarizes current progresses about the cell origins, biomaterials and advanced technology being applied to make human islet organoids, and discusses the advantages, shortcomings, and future challenges of them as well. We hope this review can offer a cross-disciplinary perspective to build human islet organoids and provide insights for tissue engineering and regenerative medicine.

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Section: Cells For Making Human Islet Organoidsmentioning

confidence: 99%

Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies

Jiang¹,

Shen²,

Liu³

et al. 2022

Theranostics

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“…Since the first demonstrations of the functional capacity of SC-β generated from T1D patient-derived iPSCs [ 104 , 106 ], most of the research in the field has been focused on the potential clinical application of stem cells for cell replacement therapy [ 258 ]. Autologous systems have certain limitations, such as the cost [ 259 ], the risk associated with de-novo generation of immunogenic epitopes during reprogramming [ 260 ] or teratoma formation from residual undifferentiated cells [ 141 ].…”

Section: Genetic Basis Of β Cell Dysfunctionmentioning

confidence: 99%

Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction

Bartolomé

2022

IJMS

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Pancreatic β cell dysfunction is a central component of diabetes progression. During the last decades, the genetic basis of several monogenic forms of diabetes has been recognized. Genome-wide association studies (GWAS) have also facilitated the identification of common genetic variants associated with an increased risk of diabetes. These studies highlight the importance of impaired β cell function in all forms of diabetes. However, how most of these risk variants confer disease risk, remains unanswered. Understanding the specific contribution of genetic variants and the precise role of their molecular effectors is the next step toward developing treatments that target β cell dysfunction in the era of personalized medicine. Protocols that allow derivation of β cells from pluripotent stem cells, represent a powerful research tool that allows modeling of human development and versatile experimental designs that can be used to shed some light on diabetes pathophysiology. This article reviews different models to study the genetic basis of β cell dysfunction, focusing on the recent advances made possible by stem cell applications in the field of diabetes research.

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“…Thus, these strategies can provide an alternative source for insulin-producing b-like cells derived from stem cells. Despite their therapeutic potential, the clinical viability of transplanting stem cell derived insulin-producing cells poses many challenges including the optimization of differentiation and maturation (46)(47)(48), graft rejection induced by one's immune system and long-term survival in vivo (49)(50)(51)(52). Although, the current transplantation location used in clinical settings is through the hepatic portal vein in the liver, there is a growing consensus that the hepatic milieu may not be hospitable for functional islet transplantation and their long-term viability, not only for cadaveric human islets (53) but also stem cell derived islets.…”

Section: Introductionmentioning

confidence: 99%

Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes

2021

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Diabetes is a complex disease that affects over 400 million people worldwide. The life-long insulin injections and continuous blood glucose monitoring required in type 1 diabetes (T1D) represent a tremendous clinical and economic burdens that urges the need for a medical solution. Pancreatic islet transplantation holds great promise in the treatment of T1D; however, the difficulty in regulating post-transplantation immune reactions to avoid both allogenic and autoimmune graft rejection represent a bottleneck in the field of islet transplantation. Cell replacement strategies have been performed in hepatic, intramuscular, omentum, and subcutaneous sites, and have been performed in both animal models and human patients. However more optimal transplantation sites and methods of improving islet graft survival are needed to successfully translate these studies to a clinical relevant therapy. In this review, we summarize the current progress in the field as well as methods and sites of islet transplantation, including stem cell-derived functional human islets. We also discuss the contribution of immune cells, vessel formation, extracellular matrix, and nutritional supply on islet graft survival. Developing new transplantation sites with emerging technologies to improve islet graft survival and simplify immune regulation will greatly benefit the future success of islet cell therapy in the treatment of diabetes.

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Applications of iPSC-derived beta cells from patients with diabetes

Cited by 72 publications

References 94 publications

Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies

Making human pancreatic islet organoids: Progresses on the cell origins, biomaterials and three-dimensional technologies

Stem Cell-Derived β Cells: A Versatile Research Platform to Interrogate the Genetic Basis of β Cell Dysfunction

Advances in Pancreatic Islet Transplantation Sites for the Treatment of Diabetes

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