Highly Selective Intraportal Transplantation of Pancreatic Islets

Juszczak, Maciej; Kooner, Paul; Pawelec, Krystian; Jones, Gareth; Hughes, Stephen J.; Kumar, Anila; Powis, Stephen H.; Press, Martin

doi:10.1016/j.jss.2008.09.026

Cited by 6 publications

(8 citation statements)

References 31 publications

(45 reference statements)

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“…Random distribution of islets after IPIT represents a major obstacle for detection of islets transplanted in experimental models [14, 15]. So we tried a new ideal model to analyse local changes of pathology and inflammation post‐transplantation of islets.…”

Section: Discussionmentioning

confidence: 99%

“…So we tried a new ideal model to analyse local changes of pathology and inflammation post‐transplantation of islets. In this model, we selectively transplant islets into the right branch of the PV, which is the first branch of the portal trunk and supplies the right anterior hepatic lobe [15, 16]. Selective islet transplantation increases the density of transplant in a fixed site (Fig.…”

Section: Discussionmentioning

confidence: 99%

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Small Islets are Essential for Successful Intraportal Transplantation in a Diabetes Mouse Model

Xia

Shao

et al. 2010

Scandinavian Journal of Immunology

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Optimization of islet transplantation protocols is necessary for improved success of treatment for type 1 diabetes. Here, we investigated whether the size of islets transplanted into the portal vein (PV) of the liver can affect engraftment in the early post‐transplantation in an experimental mouse model. Small (average diameter < 250 μm, group A) or large (average diameter > 250 μm, group B) islets (400 islet equivalents/recipient) purified from normal BALB/c mice were transplanted into syngenic recipients with diabetes induced by STZ. The percentage of mice returning to a non‐diabetic status was higher in group A (100%) than that of group B (62.5%). Focal areas of liver necrosis associated with the islets emboli were observed in both groups, but the pathology in group B was significantly worse. Multiple proinflammatory cytokines were significantly higher in group B than that of A at 3 h post‐transplantation. Our study determined that the size of islets plays a critical role in the success of intraportal islet transplantation (IPIT) and should be taken into account in future IPIT protocols for the treatment of diabetes.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Small Islets are Essential for Successful Intraportal Transplantation in a Diabetes Mouse Model

Xia

Shao

et al. 2010

Scandinavian Journal of Immunology

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“…The cell sheet technique also makes the delivery of target molecule safe. In the successful clinical trial of intraportal islet transplantation by Shapiro et al, islet transplantation was exclusively conducted via the portal vein [22,[46][47][48][49]. When the islet is administered directly through the portal vein, many cells engraft in the liver through smaller venues, and the liver can supply sufficient blood in a near-physiological insulin delivery environment.…”

Section: Discussionmentioning

confidence: 99%

Improvement of therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet

Lee

Seo

et al. 2020

Preprint

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Background: Although pancreatic islet transplantation therapy is ideal for diabetes patients, several hurdles have prevented it from becoming a standard treatment, including donor shortage and low engraftment efficacy. In this study, we prepared insulin-producing cells trans-differentiated from adult human liver cells as a new islet source. Also, cell sheets formation could improve differentiation efficiency and graft survival.Methods: Liver cells were expanded in vitro and trans-differentiated to IPCs using adenovirus vectors carrying human genes for PDX1, NEUROD1 and MAFA. IPCs were seeded on temperature-responsive culture dishes to form cell sheets. Differentiation efficiency were confirmed by ß cell-specific gene expression, insulin production, and immunohistochemistry. IPCs suspension was injected by portal vein (PV), and IPCs sheet was transplanted on the liver surface of the diabetic nude mouse. The therapeutic effect of IPC sheet was evaluated by comparing blood glucose control, weight gain, histological evaluation and hepatotoxicity with IPCs injection group. Also, cell biodistribution was assessed by in vivo/ex vivo fluorescence image tagging.Results: Insulin gene expression and protein production were significantly increased on IPC sheets compared with those in IPCs cultured on conventional culture dishes. Transplanted IPC sheets displayed significantly higher engraftment efficiency and fewer transplanted cells in other organs than injected IPCs, and also lower liver toxicity, improved blood glucose levels, and weight gain. One and two weeks following IPC sheet transplantation, immunohistochemical analyses of liver tissue revealed positive staining for PDX1 and insulin.Conclusions: In conclusion, cell sheet formation enhanced the differentiation function and maturation of IPCs in vitro. Additionally, parameters for clinical application such as distribution, therapeutic efficacy, and toxicity were favorable. The cell sheet technique may be used with IPCs derived from various cell sources in clinical applications.

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“…De Paula and other authors published several series, since the middle of the last decade till recently (DePaula et al 2008(DePaula et al , 2012Kota et al 2012;Goel et al 2011; Tinoco et al 2011;Kumar et al 2009). They discussed the outcome of a novel technique including a combination of ileal interposisition and sleeve gastrectomy.…”

Section: Ileal Interpositionmentioning

confidence: 99%

“…β-islet transplantations are less invasive, via the portal vein (Juszczak et al 2009). Intravenous administration of mesenchymal stem cells is totally non-invasive, unlike bariatric and metabolic surgery for type II diabetes (Si et al 2012).…”

Section: How Are Other Surgical Options Comparable With Cell Therapy mentioning

confidence: 99%

Obesity and Diabetes

Faintuch¹,

Faintuch²

2015

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Highly Selective Intraportal Transplantation of Pancreatic Islets

Cited by 6 publications

References 31 publications

Small Islets are Essential for Successful Intraportal Transplantation in a Diabetes Mouse Model

Small Islets are Essential for Successful Intraportal Transplantation in a Diabetes Mouse Model

Improvement of therapeutic capacity of insulin-producing cells trans-differentiated from human liver cells using engineered cell sheet

Obesity and Diabetes

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