The Fate of Allogeneic Pancreatic Islets following Intraportal Transplantation: Challenges and Solutions

Li, Xinyu; Meng, Qiang; Zhang, Lei

doi:10.1155/2018/2424586

Cited by 34 publications

(24 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytoprotective effects of hAECs against hypoxia‐induced damage to islet cell viability and function are consistent with what we previously described in insulin‐secreting organoids combining dissociated islet cells with hAECs (IC‐hAEC). In this study, improved viability and function of organoids after hypoxia were associated with the upregulation of hypoxia‐inducible factor 1‐alpha (HIF‐1α), which is involved in regulatory protection mechanisms triggered during hypoxic events …”

Section: Discussionmentioning

confidence: 98%

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Lebreton

Bellofatto

Wassmer

et al. 2020

American Journal of Transplantation

View full text Add to dashboard Cite

Hypoxia is a major cause of considerable islet loss during the early posttransplant period. Here, we investigate whether shielding islets with human amniotic epithelial cells (hAECs), which possess anti‐inflammatory and regenerative properties, improves islet engraftment and survival. Shielded islets were generated on agarose microwells by mixing rat islets (RIs) or human islets (HI) and hAECs (100 hAECs/IEQ). Islet secretory function and viability were assessed after culture in hypoxia (1% O2) or normoxia (21% O2) in vitro. In vivo function was evaluated after transplant under the kidney capsule of diabetic immunodeficient mice. Graft morphology and vascularization were evaluated by immunohistochemistry. Both shielded RIs and HIs show higher viability and increased glucose‐stimulated insulin secretion after exposure to hypoxia in vitro compared with control islets. Transplant of shielded islets results in considerably earlier normoglycemia and vascularization, an enhanced glucose tolerance, and a higher β cell mass. Our results show that hAECs have a clear cytoprotective effect against hypoxic damages in vitro. This strategy improves β cell mass engraftment and islet revascularization, leading to an improved capacity of islets to reverse hyperglycemia, and could be rapidly applicable in the clinical situation seeing that the modification to HIs are minor.

show abstract

Section: Discussionmentioning

confidence: 98%

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Lebreton

Bellofatto

Wassmer

et al. 2020

American Journal of Transplantation

View full text Add to dashboard Cite

show abstract

“…Inflammation and autoimmunity are one of the causes for the initiation of β-cell destruction during the development of T1D. Transplanted pancreatic islets themselves can also release pro-inflammatory cytokines, which play a significant role in cell failure and death, during and post-islet transplantation 43,44,46 . Thus, identifying factors that can help improve the preservation of pancreatic β-cell mass is in demand to improve islet transplant outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…Allogenic-ICT can be a curative therapy for T1D, while auto-ICT can preserve the endocrine function of patients undergoing pancreatectomy. However, the major problem with any islet transplantation, particularly for T1D, is a significant loss of islet viability both early and late after the transplant 12,43–45 . In T1D patients, only ~50% of successful islet transplant recipients maintain insulin independence after two years.…”

Section: Discussionmentioning

confidence: 99%

Cholecystokinin Suppresses β-Cell Apoptosis, Including in Human Islets in a Transplant Model

Souza²,

Umhoefer³

et al. 2021

Preprint

View full text Add to dashboard Cite

Loss of functional pancreatic β-cell mass and increased β-cell apoptosis are fundamental to the pathophysiology of both type 1 and type 2 diabetes. Pancreatic islet transplantation has the potential to cure type 1 diabetes but is often ineffective due to the death of the islet graft within the first few years after transplant. Therapeutic strategies to directly target pancreatic β-cell survival are needed to prevent and treat diabetes and to improve islet transplant outcomes. Reducing β-cell apoptosis is also a therapeutic strategy for type 2 diabetes. Cholecystokinin (CCK) is a peptide hormone typically produced in the gut after food intake, with positive effects on obesity and glucose metabolism in mouse models and human subjects. We have previously shown that pancreatic islets also produce CCK. The production of CCK within the islet promotes β-cell survival in rodent models of diabetes and aging. Now, we demonstrate a direct effect of CCK to reduce cytokine-mediated apoptosis in a β-cell line and in isolated mouse islets in a receptor-dependent manner. However, whether CCK can protect human β-cells was previously unknown. Here, we report that CCK can also reduce cytokine-mediated apoptosis in isolated human islets and CCK treatment in vivo decreases β-cell apoptosis in human islets transplanted into the kidney capsule of diabetic NOD/SCID mice. Collectively, these data identify CCK as a novel therapy that can directly promote β-cell survival in human islets and has therapeutic potential to preserve β-cell mass in diabetes and as an adjunct therapy after transplant.One Sentence SummaryCholecystokinin ameliorates pancreatic β-cell death under models of stress and after transplant of human islets.

show abstract

“…The need for numerous islets to achieve euglycemia and progressive deterioration in islet function over time represents significant barriers [ 4 , 29 ]. Islets injection through portal vein may contribute to islet dysfunction and loss [ 30 ]. Thus, the development of alternative islet transplantation sites is a priority.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Multi-Layered Pancreatic Islets and Adipose-Derived Stem Cell Sheets Transplanted on Various Sites for Diabetes Treatment

Lee

Kim

et al. 2020

Cells

View full text Add to dashboard Cite

Islet cell transplantation is considered an ideal treatment for insulin-deficient diabetes, but implantation sites are limited and show low graft survival. Cell sheet technology and adipose-derived stem cells (ADSCs) can be useful tools for improving islet cell transplantation outcomes since both can increase implantation efficacy and graft survival. Herein, the optimal transplantation site in diabetic mice was investigated using islets and stem cell sheets. We constructed multi-layered cell sheets using rat/human islets and human ADSCs. Cell sheets were fabricated using temperature-responsive culture dishes. Islet/ADSC sheet (AI sheet) group showed higher viability and glucose-stimulated insulin secretion than islet-only group. Compared to islet transplantation alone, subcutaneous AI sheet transplantation showed better blood glucose control and CD31+ vascular traits. Because of the adhesive properties of cell sheets, AI sheets were easily applied on liver and peritoneal surfaces. Liver or peritoneal surface grafts showed better glucose control, weight gain, and intraperitoneal glucose tolerance test (IPGTT) profiles than subcutaneous site grafts using both rat and human islets. Stem cell sheets increased the therapeutic efficacy of islets in vivo because mesenchymal stem cells enhance islet function and induce neovascularization around transplanted islets. The liver and peritoneal surface can be used more effectively than the subcutaneous site in future clinical applications.

show abstract

The Fate of Allogeneic Pancreatic Islets following Intraportal Transplantation: Challenges and Solutions

Cited by 34 publications

References 112 publications

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Shielding islets with human amniotic epithelial cells enhances islet engraftment and revascularization in a murine diabetes model

Cholecystokinin Suppresses β-Cell Apoptosis, Including in Human Islets in a Transplant Model

Evaluation of Multi-Layered Pancreatic Islets and Adipose-Derived Stem Cell Sheets Transplanted on Various Sites for Diabetes Treatment

Contact Info

Product

Resources

About