Toward Engineering a Novel Transplantation Site for Human Pancreatic Islets

Smink, Alexandra M.; Faas, Marijke M.; Vos, Paul de

doi:10.2337/db12-1553

Cited by 46 publications

(44 citation statements)

References 50 publications

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“…It is also important to note that the site of islet infusion used by most studies in the literature is the portal vein, which is not the most adequate place for cell infusion (70). It is estimated that 50-70% of islets are destroyed in the period immediately following the transplant, given the unique characteristics of the liver and the damaging effect of immunosuppressive drugs on insulin secretion and islet viability (71).…”

Section: Islet Transplantation In Patients With "Brittle T1dm"mentioning

confidence: 99%

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Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

Rheinheimer

Bauer

Silveiro

et al. 2015

Arch. Endocrinol. Metab.

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Type 1 diabetes mellitus (T1DM) is associated with chronic complications that lead to high morbidity and mortality rates in young adults of productive age. Intensive insulin therapy has been able to reduce the likelihood of the development of chronic diabetes complications. However, this treatment is still associated with an increased incidence of hypoglycemia. In patients with "brittle T1DM" , who have severe hypoglycemia without adrenergic symptoms (hypoglycemia unawareness), islet transplantation may be a therapeutic option to restore both insulin secretion and hypoglycemic perception. The Edmonton group demonstrated that most patients who received islet infusions from more than one donor and were treated with steroid-free immunosuppressive drugs displayed a considerable decline in the initial insulin independence rates at eight years following the transplantation, but showed permanent C-peptide secretion, which facilitated glycemic control and protected patients against hypoglycemic episodes. Recently, data published by the Collaborative Islet Transplant Registry (CITR) has revealed that approximately 50% of the patients who undergo islet transplantation are insulin independent after a 3-year follow-up. Therefore, islet transplantation is able to successfully decrease plasma glucose and HbA1c levels, the occurrence of severe hypoglycemia, and improve patient quality of life. The goal of this paper was to review the human islet isolation and transplantation processes, and to describe the establishment of a human islet isolation laboratory at the Endocrine Division of the Hospital de Clínicas de Porto Alegre -Rio Grande do Sul, Brazil. Arch Endocrinol Metab. 2015;59(2):161-70

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Section: Islet Transplantation In Patients With "Brittle T1dm"mentioning

confidence: 99%

“…Currently, other infusion sites and methods have been studied in an attempt to develop techniques that ensure a better engraftment of the islets. One example is the encapsulation, which allows for revascularization while sparing the islets from environmental damage (70).…”

Section: Islet Transplantation In Patients With "Brittle T1dm"mentioning

confidence: 99%

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

Rheinheimer

Bauer

Silveiro

et al. 2015

Arch. Endocrinol. Metab.

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“…Ectopic organogenesis can be an alternative approach to provide compensatory function for the damaged organ [2,3]. Unfortunately, although several extravascular and a few immunoprivileged sites have been considered as potential ectopic transplantation sites for organs like pancreas [4] and liver [5], ectopic sites for kidney reconstruction have not yet been fully examined.…”

Section: Introductionmentioning

confidence: 99%

The Lymph Node as a New Site for Kidney Organogenesis

Francipane

Lagasse

2015

Stem Cells Translational Medicine

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The shortage of organs for kidney transplantation has created the need to develop new strategies to restore renal structure and function. Given our recent finding that the lymph node (LN) can serve as an in vivo factory to generate or sustain complex structures like liver, pancreas, and thymus, we investigated whether it could also support kidney organogenesis from mouse renal embryonic tissue (metanephroi). Here we provide the first evidence that metanephroi acquired a mature phenotype upon injection into LN, and host cells likely contributed to this process. Urine-like fluid-containing cysts were observed in several grafts 12 weeks post-transplantation, indicating metanephroi transplants' ability to excrete products filtered from the blood. Importantly, the kidney graft adapted to a loss of host renal mass, speeding its development. Thus, the LN might provide a unique tool for studying the mechanisms of renal maturation, cell proliferation, and fluid secretion during cyst development. Moreover, we provide evidence that inside the LN, short-term cultured embryonic kidney cells stimulated with the Wnt agonist R-Spondin 2 gave rise to a monomorphic neuron-like cell population expressing the neuronal 200-kDa neurofilament heavy marker. This finding indicates that the LN might be used to validate the differentiation potential of candidate stem cells in regenerative nephrology. STEM CELLS TRANSLATIONAL MEDICINE 2015;4:295-307

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“…27 With adequate vascularization one might take advantage of other advances in polymer-based substrates for islet cell growth. 28,29 Repurposing of organ scaffolds is particularly promising for pancreatic islet cells. We believe that the kidney's highly vascular structure will permit viability and functionality of the large numbers of cells that are needed by islets for the required cell-to-cell signaling through such pathways as homeobox-1.…”

Section: Discussionmentioning

confidence: 99%

Repurposed biological scaffolds: kidney to pancreas

et al. 2015

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Advances in organ regeneration have been facilitated by gentle decellularization protocols that maintain distinct tissue compartments, and thereby allow seeding of blood vessels with endothelial lineages separate from populations of the parenchyma with tissue-specific cells. We hypothesized that a reconstituted vasculature could serve as a novel platform for perfusing cells derived from a different organ: thus discordance of origin between the vascular and functional cells, leading to a hybrid repurposed organ. The need for a highly vascular bed is highlighted by tissue engineering approaches that involve transplantation of just cells, as attempted for insulin production to treat human diabetes. Those pancreatic islet cells present unique challenges since large numbers are needed to allow the cell-to-cell signaling required for viability and proper function; however, increasing their number is limited by inadequate perfusion and hypoxia. As proof of principle of the repurposed organ methodology we harnessed the vasculature of a kidney scaffold while seeding the collecting system with insulin-producing cells. Pig kidneys were decellularized by sequential detergent, enzymatic and rinsing steps. Maintenance of distinct vascular and collecting system compartments was demonstrated by both fluorescent 10 micron polystyrene microspheres and cell distributions in tissue sections. Sterilized acellular scaffolds underwent seeding separately via the artery (fibroblasts or endothelioma cells) and retrograde (murine βTC-tet cells) up the ureter. After three-day bioreactor incubation, histology confirmed separation of cells in the vasculature from those in the collecting system. βTC-tet clusters survived in tubules, glomerular Bowman's space, demonstrated insulin immunolabeling, and thereby supported the feasibility of kidney-to-pancreas repurposing.

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Toward Engineering a Novel Transplantation Site for Human Pancreatic Islets

Cited by 46 publications

References 50 publications

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

Human pancreatic islet transplantation: an update and description of the establishment of a pancreatic islet isolation laboratory

The Lymph Node as a New Site for Kidney Organogenesis

Repurposed biological scaffolds: kidney to pancreas

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