Maintenance of Normoglycemia in Diabetic Mice by Subcutaneous Xenografts of Encapsulated Islets

Lacy, Paul E.; Hegre, Orion D.; Gerasimidi-Vazeou, Andriani; Gentile, Frank T.; Dionne, Keith E.

doi:10.1126/science.1763328

Cited by 335 publications

(140 citation statements)

References 22 publications

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“…This was not so much the consequence of fibrotic overgrowth but rather of aggregation of the encapsulated tissue into large clumps [18]. Extensive necrosis occurred in the centre of the clumps as a result of diffusion limitations for nutrients.…”

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

“…Extensive necrosis occurred in the centre of the clumps as a result of diffusion limitations for nutrients. This problem was readily solved by preventing contact between the encapsulated tissue elements through permanent solitude immobilization in a matrix such as collagen [33,34], Ca-alginate [18], or chitosan [11]. Usually in PAN-PVC fibres islets are immobilized in alginate.…”

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

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Considerations for successful transplantation of encapsulated pancreatic islets

2002

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A major challenge in the treatment of Type I (insulindependent) diabetes mellitus is the prevention of late complications, and thereby improvement of the quality of patient life. There is no dispute that euglycaemia is of essential importance to reach that goal. Euglycaemia can be achieved by insulin treatment and the results of the Diabetes control and complications trial clearly show that insulin treatment delays the onset and reduces the progression of diabetic complications [1]. Intensified treatment, however, is not a simple chore because it requires multiple daily injections, frequent monitoring, dosage adaptations and, thus, patient compliance. It is also associated with frequent episodes of severe hypoglycaemia and with glycaemic unawareness. A different approach to euglycaemia is to provide the diabetic patient with an endogenous rather than an exogenous source of insulin by the transplantation of the endocrine pancreatic tissue. Pancreatic organ transplantation is now an es- Diabetologia (2002) AbstractEncapsulation of pancreatic islets allows for transplantion in the absence of immunosuppression. The technology is based on the principle that transplanted tissue is protected for the host immune system by an artificial membrane. Encapsulation offers a solution to the shortage of donors in clinical islet transplantation because it allows animal islets or insulin-producing cells engineered from stem cells to be used. During the past two decades three major approaches to encapsulation have been studied. These include intravascular macrocapsules, which are anastomosed to the vascular system as AV shunt; extravascular macrocapsules, which are mostly diffusion chambers transplanted at different sites; and extravascular microcapsules transplanted in the peritoneal cavity. The advantages and pitfalls of these three approaches are discussed and compared in the light of their applicability to clinical islet transplantation. All systems have been shown to be successful in preclinical studies but not all approaches meet the technical or physiological requirements for application in human beings. The extravascular approach has advantages over the intravascular because since it is associated with less complications such as thrombosis and infection. Microcapsules, due to their spatial characteristics, have a better diffusion capacity than macrocapsules. Recent progress in biocompatibility of microcapsules has brought this technology close to clinical application. Critical issues such as limitations in the functional performance and survival are being discussed. The latest results show that both issues can be solved by the transplantation of microencapsulated islets close to blood vessels in prevascularized solid supports. [Diabetologia (2002) 45: 159±173]

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Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

Section: Macroencapsulation Of Pancreatic Isletsmentioning

confidence: 99%

Considerations for successful transplantation of encapsulated pancreatic islets

2002

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“…In conclusion, the membranes applied ensured the sules (13,14,17,18). In the preparation of HF the solvent is removed directly from the membrane during its washbacteria growth only within the HF space when cultured …”

Section: Evaluation Of Gfp Expression In Vitromentioning

confidence: 99%

Survival Analysis of Escherichia coli Encapsulated in a Hollow Fiber Membrane In Vitro and In Vivo: Preliminary Report

Wdowiak

Kosek

et al. 2005

Cell Transplant

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The purpose of the observations was the viability and quality evaluation of E. coli bacteria encapsulated in hollow fiber membranes (HF) in short in vivo and in vitro experiments. A polypropylene, surface-modified hollow fiber was applied for immunoisolation of E. coli bacteria transfected with a green fluorescent protein (E. coli GFPI). The presence of GFP fluorescence of organisms was assessed with the use of flow cytometry. The E. coli GFPIs were then observed for the period of 5 days in in vitro experiments in the culture medium. A single IPTG (isopropyl β-D-1-thiogalactopyranoside) induction of GFP gene appeared to be adequate for an expression of GFP protein for 5 days. The GFP expression values observed for E. coli GFPs encapsulated in HF during culture in different culture media were comparable. The survival of E. coli GFPIs encapsulated in HF after 1, 2, 4, or 5 days of subcutaneous implantation into mice was evaluated. The explanted E. coli GFPIs exhibited mean expression 603 ± 17 (n = 32) units of fluorescence during the implantation period. The values obtained were comparable for selected days of observation. It was observed that the membranes applied ensured the bacteria growth within the HF's space only.

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“…Recently, implantation of a cell-laden hydrogel scaffold has been developed as an alternative and appealing approach for controlled, sustainable in vivo growth factor delivery 3 . Here, hydrogel scaffolds serve as a barrier to isolate implanted cells from the immune system, preventing immune-rejection 4 while allowing bidirectional diffusion of oxygen, nutrients, and cell products and wastes 5 . Advances in hydrogel scaffold development has facilitated cell encapsul ation as a potential therapy for type 1 diabetes 6 , cartilage 7 and bone regeneration 8 , osteroarthritis 9 , Parkinsonian symptoms 10 and cancer 11 .…”

Section: Introductionmentioning

confidence: 99%

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

et al. 2017

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Cell encapsulation within photopolymerized polyethylene glycol (PEG)-based hydrogel scaffolds has been demonstrated as a robust strategy for cell delivery, tissue engineering, regenerative medicine, and developing in vitro platforms to study cellular behavior and fate. Strategies to achieve spatial and temporal control over PEG hydrogel mechanical properties, chemical functionalization, and cytocompatibility have advanced considerably in recent years. Recent microfluidic technologies have enabled the miniaturization of PEG hydrogels, thus enabling the fabrication of miniaturized cell-laden vehicles. However, rapid oxygen diffusive transport times on the microscale dramatically inhibit chain growth photopolymerization of polyethylene glycol diacrylate (PEGDA), thus decreasing the viability of cells encapsulated within these microstructures. Another promising PEG-based scaffold material, PEG norbornene (PEGNB), is formed by a step-growth photopolymerization and is not inhibited by oxygen. PEGNB has also been shown to be more cytocompatible than PEGDA and allows for orthogonal addition reactions. The step-growth kinetics, however, are slow and therefore challenging to fully polymerize within droplets flowing through microfluidic devices. Here, we describe a microfluidic-based droplet fabrication platform that generates consistently monodisperse cell-laden water-in-oil emulsions. Microfluidically generated PEGNB droplets are collected and photopolymerized under UV exposure in bulk emulsions. In this work, we compare this microfluidic-based cell encapsulation platform with a vortex-based method on the basis of microgel size, uniformity, post-encapsulation cell viability and long-term cell viability. Several factors that influence post-encapsulation cell viability were identified. Finally, long-term cell viability achieved by this platform was compared to a similar cell encapsulation platform using PEGDA. We show that this PEGNB microencapsulation platform is capable of generating cell-laden hydrogel microspheres at high rates with well-controlled size distributions and high long-term cell viability.

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Maintenance of Normoglycemia in Diabetic Mice by Subcutaneous Xenografts of Encapsulated Islets

Cited by 335 publications

References 22 publications

Considerations for successful transplantation of encapsulated pancreatic islets

Considerations for successful transplantation of encapsulated pancreatic islets

Survival Analysis of Escherichia coli Encapsulated in a Hollow Fiber Membrane In Vitro and In Vivo: Preliminary Report

A microfluidic-based cell encapsulation platform to achieve high long-term cell viability in photopolymerized PEGNB hydrogel microspheres

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