Alternative Transplantation Sites for Pancreatic Islet Grafts

Cantarelli, Elisa; Piemonti, Lorenzo

doi:10.1007/s11892-011-0216-9

Cited by 124 publications

(103 citation statements)

References 118 publications

(102 reference statements)

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“…Several sites and implant designs have been explored. Popular sites include the kidney capsule, omental pouch, epidydimal fat pad, intramuscular, and peritoneum (see reviews 8,9 ). Device configurations for housing islets have ranged from beads, to rods, to sheets, to disks, with various materials employed from degradable extracellular matrices to alginate hydrogels (see reviews [10][11][12] ).…”

mentioning

confidence: 99%

Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site

Brady

Martino

Pedraza

et al. 2013

Tissue Engineering Part A

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The transplantation of allogeneic islets in recent clinical trials has shown substantial promise as a therapy for type 1 diabetes; however, long-term insulin independence remains inadequate. This has been largely attributed to the current intravascular, hepatic transplant site, which exposes islets to mechanical and inflammatory stresses. A highly macroporous scaffold, housed within an alternative transplant site, can support an ideal environment for islet transplantation by providing three-dimensional distribution of islets, while permitting the infiltration of host vasculature. In the present study, we sought to evaluate the synergistic effect of a proangiogenic hydrogel loaded within the void space of a macroporous poly(dimethylsiloxane) (PDMS) scaffold on islet engraftment. The fibrin-based proangiogenic hydrogel tested presents platelet derived growth factor (PDGF-BB), via a fibronectin (FN) fragment containing growth factor and major integrin binding sites in close proximity. The combination of the proangiogenic hydrogel with PDMS scaffolds resulted in a significant decrease in the time to normoglycemia for syngeneic mouse islet transplants. This benefit was associated with an observed increase in competent vessel branching, as well as mature intraislet vessels. Overall, the addition of the proangiogenic factor PDGF-BB, delivered via the FN fragmentfunctionalized hydrogel, positively influenced the efficiency of engraftment. These characteristics, along with its ease of retrieval, make this combination of a biostable macroporous scaffold and a degradable proangiogenic hydrogel a supportive structure for insulin-producing cells implanted in extrahepatic sites.

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mentioning

confidence: 99%

Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site

Brady

Martino

Pedraza

et al. 2013

Tissue Engineering Part A

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“…At the same time, it could realize continuous function, which is of particular interest for researchers. It has been demonstrated in experimental animal models that islet grafts transplantation with or without the strategy of bioengineering in a number of extrahepatic sites, even though translation in clinic for some is unclear [43][44][45]. Numerous sites have been proposed and tested, both experimentally and in some cases clinically, including the liver, kidney subcapsule, bone marrow, immune privileged sites, and peritoneum spaces.…”

Section: Current Alternative Sites For Islet Transplantationmentioning

confidence: 99%

Xenotransplantation for Islets from Clinical Side

Wang¹,

Liang²,

Nie³

et al. 2017

Xenotransplantation - New Insights

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Islet transplantation can eliminate severe hypoglycemia symptoms caused by conventional treatment, and has the advantages of less trauma and complications, which is considered as the most promising treatment for type 1 diabetes mellitus (T1DM). Regulatory guidance is needed for a standard pig source. In section 1, the regulation of medical grade designed pathogen free (DPF) donor pig for clinical xenotransplantation consists of five parts: genetic quality control, microbiological surveillance, formula feeds, specification of pathological diagnosis, and requirements of environment and housing facilities. In section 2, we present the current approach and progress in pig donor selecting, pancreatic digestion, isolation and preparation of porcine islet grafts, identification and quality assessment of final islet product in clinical trials. The liver is currently the most preferred site for islet transplantation, even though it is far from ideal. A large number of alternative sites have been used for islet transplantation in experimental animal models to provide improved engraftment and long-term survival. In Section 3, we introduce some commonly used sites in xenotransplantation. The benefits and drawbacks of each parameter above are discussed in an attempt to decide which is the most suitable for clinical use and to direct future research.

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“…The freedom from volume constraint for transplant placement in the peritoneal cavity makes it an attractive choice for both free and encapsulated islet transplant [66]. Clinically, the peritoneal cavity is currently undergoing trials mainly for encapsulated islets [67].…”

Section: Peritoneal Cavitymentioning

confidence: 99%

“…Clinically, the peritoneal cavity is currently undergoing trials mainly for encapsulated islets [67]. There's a delay in systemic insulin distribution from islets placed in the peritoneal cavity [68], and a significantly larger number of islets is needed to result in cure when compared to intraportal transplantation [66].…”

Section: Peritoneal Cavitymentioning

confidence: 99%

See 1 more Smart Citation

Strategies in Preventing Diabetes after Pancreatectomy Using Islet Auto- and Allo-Transplantation

Tucker¹

2017

Int J Transplant Res Med

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Over the years, pancreatectomy has been the primary treatment for chronic pancreatitis. Since the 1970s, total pancreatectomy has been shown to be effective at relieving pain that was experienced due to chronic pancreatitis. However, total pancreatectomy alone has the significant side effect of post-surgical diabetes. To treat post-pancreatectomy diabetes, total pancreatectomy was combined with Islet Autotransplantation (TP-IAT), which resulted in a much lower mortality rate compared to total pancreatectomy alone. Such operations require an expertise in islet isolation techniques, and thus this procedure is not widely performed.Since 2000, TP-IAT success has continued to increase. Improvement in islet isolation yield, better transplant techniques, and changes to post-operative care, have improved the islet engraftment and long-term survival rate. The Edmonton protocol, introduced in 2000, offers the option of islet allograft to complement total pancreatectomy. This protocol uses improved immunosuppressive regimens to improve islet allograft tolerance and accomplished higher rate of insulin independence. This advance led to improved clinical outcome after TP-IAT, including islet graft success after transplantation, reduction in narcotic use, pain, and improvement in quality of life.In this paper, we evaluated the history and advances of clinical islet transplant post-pancreatectomy. We also evaluated alternative transplant sites that are currently explored for islet graft, which are expected to offer improved islet engraftment and survival, and improved islet graft function.

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Alternative Transplantation Sites for Pancreatic Islet Grafts

Cited by 124 publications

References 118 publications

Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site

Proangiogenic Hydrogels Within Macroporous Scaffolds Enhance Islet Engraftment in an Extrahepatic Site

Xenotransplantation for Islets from Clinical Side

Strategies in Preventing Diabetes after Pancreatectomy Using Islet Auto- and Allo-Transplantation

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