Real-Time Bioluminescence Imaging of Macroencapsulated Fibroblasts Reveals Allograft Protection in Rhesus Monkeys (Macaca mulatta)

Tarantal, Alice F.; Lee, C Chang I.; Itkin-Ansari, Pamela

doi:10.1097/tp.0b013e3181a9ee6c

Cited by 30 publications

(30 citation statements)

References 14 publications

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“…The idea is that isletlike structures form and become functionally responsive to glucose in vivo. A comparable encapsulation approach had been shown to protect human fibroblast allografts from rejection in rhesus monkeys (423). Also, implantation of primary murine beta-cells encapsulated in a similar device could ameliorate diabetes in NOD mice (242).…”

Section: Stem Cellsmentioning

confidence: 99%

Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies

Belle

Coppieters

Herrath

2011

Physiological Reviews

854

695

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Type 1 diabetes (T1D) is a chronic autoimmune disease in which destruction or damaging of the beta-cells in the islets of Langerhans results in insulin deficiency and hyperglycemia. We only know for sure that autoimmunity is the predominant effector mechanism of T1D, but may not be its primary cause. T1D precipitates in genetically susceptible individuals, very likely as a result of an environmental trigger. Current genetic data point towards the following genes as susceptibility genes: HLA, insulin, PTPN22, IL2Ra, and CTLA4. Epidemiological and other studies suggest a triggering role for enteroviruses, while other microorganisms might provide protection. Efficacious prevention of T1D will require detection of the earliest events in the process. So far, autoantibodies are most widely used as serum biomarker, but T-cell readouts and metabolome studies might strengthen and bring forward diagnosis. Current preventive clinical trials mostly focus on environmental triggers. Therapeutic trials test the efficacy of antigen-specific and antigen-nonspecific immune interventions, but also include restoration of the affected beta-cell mass by islet transplantation, neogenesis and regeneration, and combinations thereof. In this comprehensive review, we explain the genetic, environmental, and immunological data underlying the prevention and intervention strategies to constrain T1D.

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Section: Stem Cellsmentioning

confidence: 99%

Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies

Belle

Coppieters

Herrath

2011

Physiological Reviews

854

695

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“…In order to establish pre-implantation conditions leading to long-term, high-density survival of cells in the flat sheet encapsulation device, we used a luciferase reporter system as previously described [6]. A stable C2C12 cell line expressing the firefly luciferase under the pgk-1 promoter was generated by lentiviral transduction (Fig.…”

Section: Monitoring Of Cell Survival Using the Luciferase Reportermentioning

confidence: 99%

“…Bioluminescence produced by luciferase-expressing C2C12 myoblasts is used to longitudinally monitor cells implanted in the macrocapsule [6], and determine the conditions leading to long-term cell survival inside the device.…”

Section: Introductionmentioning

confidence: 99%

A high-capacity cell macroencapsulation system supporting the long-term survival of genetically engineered allogeneic cells

Lathuilière¹,

Cosson²,

Lütolf³

et al. 2014

Biomaterials

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a b s t r a c tThe rapid increase in the number of approved therapeutic proteins, including recombinant antibodies, for diseases necessitating chronic treatments raises the question of the overall costs imposed on healthcare systems. It is therefore important to investigate alternative methods for recombinant protein administration. The implantation of genetically engineered cells is an attractive strategy for the chronic long-term delivery of recombinant proteins. Here, we have developed a high-capacity cell encapsulation system for the implantation of allogeneic myoblasts, which survive at high density for at least one year. This flat sheet device is based on permeable polypropylene membranes sealed to a mechanically resistant frame which confine cells seeded in a tailored biomimetic poly(ethylene glycol) (PEG)-based hydrogel matrix. In order to quantitate the number of cells surviving in the device and optimize initial conditions leading to high-density survival, we implant devices containing C2C12 mouse myoblasts expressing a luciferase reporter in the mouse subcutaneous tissue. We show that initial cell load, hydrogel stiffness and permeable membrane porosity are critical parameters to achieve long-term implant survival and efficacy. Optimization of these parameters leads to the survival of encapsulated myogenic cells at high density for several months, with minimal inflammatory response and dense neovascularization in the adjacent host tissue. Therefore, this encapsulation system is an effective platform for the implantation of genetically engineered cells in allogeneic conditions, which could be adapted to the chronic administration of recombinant proteins.

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“…In order to obviate the need for immunosuppressive treatments in β-cell transplantation an encapsulation device has been created that is not immunogenic and protects the transplanted cells within the device from autoreactive as well alloreactive immune attacks via a special membrane. In mice and Rhesus Macaques, this device has been shown to protect transplanted encapsulated allogeneic cells from being destroyed by the host's immune system [33,34].…”

Section: Transplantation Of β-Cellsmentioning

confidence: 99%