Continuous and High-Level in Vivo Delivery of Endostatin from Recombinant Cells Encapsulated in TheraCyte® Immunoisolation Devices

Malavasi, N.V.; Rodrigues, Daiana Elias; Chammas, Roger; Chura-Chambi, Rosa Maria; Barbuto, J. A. M.; Balduino, Keli N.; Nonogaki, Suely; Morganti, Lígia

doi:10.3727/096368909x480927

Cited by 9 publications

(7 citation statements)

References 22 publications

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“…As one trial to tackle the absorption, it is necessary to optimize the materials for the pouched-device in terms of low absorption property and high biocompatibility [33] , [34] , [35] . It is reported that the pouched-devices have a property to induce vascularization in the transplantation site [35] , [36] , [37] . Base on them, the PTFE membrane was used in the present study.…”

Section: Discussionmentioning

confidence: 99%

Insulin secretion of mixed insulinoma aggregates-gelatin hydrogel microspheres after subcutaneous transplantation

Inoo

Bando

Tabata

2018

Regenerative Therapy

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IntroductionThe objective of this study is to evaluate the insulin secretion of mixed aggregates of insulinoma cells (INS-1) and gelatin hydrogel microspheres after their subcutaneous transplantation.MethodsGelatin hydrogel microspheres were prepared by the conventional w/o emulsion method. Cell aggregates mixed with or without the hydrogel microspheres were encapsulated into a pouched-device of polytetrafluoroethylene membrane. An agarose hydrogel or MedGel™ incorporating basic fibroblast growth factor (bFGF) was subcutaneously implanted to induce vascularization. After the vascularization induction, cell aggregates encapsulated in the pouched-device was transplanted.ResultsThe vascularization had the potential to enable transplanted cell aggregates to enhance the level of insulin secretion compared with those of no vascularization induction. In addition, the insulin secretion of cell aggregates was significantly promoted by the mixing of gelatin hydrogel microspheres even in the pouched-device encapsulated state.ConclusionIt is possible that the microspheres mixing gives cells in aggregates better survival condition, resulting in promoted insulin secretion.

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Section: Discussionmentioning

confidence: 99%

Insulin secretion of mixed insulinoma aggregates-gelatin hydrogel microspheres after subcutaneous transplantation

Inoo

Bando

Tabata

2018

Regenerative Therapy

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“…Throughout the two-month study, constant and high endostatin levels of up to 3.7 μg/ml were detected in the plasma of the mice implanted with the devices [15]. The use of CHO engineered cells, which apparently are more resistant than LM to the hypoxic microenvironment of the immunoisolation devices is other alternative to keep endostatin serum levels.…”

Section: Discussionmentioning

confidence: 99%

Anti-tumor therapy with macroencapsulated endostatin producer cells

et al. 2010

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BackgroundTheracyte is a polytetrafluoroethylene membrane macroencapsulation system designed to induce neovascularization at the tissue interface, protecting the cells from host's immune rejection, thereby circumventing the problem of limited half-life and variation in circulating levels. Endostatin is a potent inhibitor of angiogenesis and tumor growth. Continuous delivery of endostatin improves the efficacy and potency of the antitumoral therapy. The purpose of this study was to determine whether recombinant fibroblasts expressing endostatin encapsulated in Theracyte immunoisolation devices can be used for delivery of this therapeutic protein for treatment of mice bearing B16F10 melanoma and Ehrlich tumors.ResultsMice were inoculated subcutaneously with melanoma (B16F10 cells) or Ehrlich tumor cells at the foot pads. Treatment began when tumor thickness had reached 0.5 mm, by subcutaneous implantation of 107 recombinant encapsulated or non-encapsulated endostatin producer cells. Similar melanoma growth inhibition was obtained for mice treated with encapsulated or non-encapsulated endostatin-expressing cells. The treatment of mice bearing melanoma tumor with encapsulated endostatin-expressing cells was decreased by 50.0%, whereas a decrease of 56.7% in tumor thickness was obtained for mice treated with non-encapsulated cells. Treatment of Ehrlich tumor-bearing mice with non-encapsulated endostatin-expressing cells reduced tumor thickness by 52.4%, whereas lower tumor growth inhibition was obtained for mice treated with encapsulated endostatin-expressing cells: 24.2%. Encapsulated endostatin-secreting fibroblasts failed to survive until the end of the treatment. However, endostatin release from the devices to the surrounding tissues was confirmed by immunostaining. Decrease in vascular structures, functional vessels and extension of the vascular area were observed in melanoma microenvironments.ConclusionsThis study indicates that immunoisolation devices containing endostatin-expressing cells are effective for the inhibition of the growth of melanoma and Ehrlich tumors.Macroencapsulation of engineered cells is therefore a reliable platform for the refinement of innovative therapeutic strategies against tumors.

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“…A commonly used commercial macrocapsule is the TheraCyte device, which is made of bilayered polytetrafluoroethylene (PTFE) membranes (Sörenby et al, 2008;Malavasi et al, 2010;Kirk et al, 2014). The outer membrane of the TheraCyte device is designed for strength and to facilitate neovascularization, and the inner membrane provides immune protection.…”

Section: Current Approachesmentioning

confidence: 99%

Treatment of diabetes with encapsulated pig islets: an update on current developments

Zhu

Liu

et al. 2015

J. Zhejiang Univ. Sci. B

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Abstract:The potential use of allogeneic islet transplantation in curing type 1 diabetes mellitus has been adequately demonstrated, but its large-scale application is limited by the short supply of donor islets and the need for sustained and heavy immunosuppressive therapy. Encapsulation of pig islets was therefore suggested with a view to providing a possible alternative source of islet grafts and avoiding chronic immunosuppression and associated adverse or toxic effects. Nevertheless, several vital elements should be taken into account before this therapy becomes a clinical reality, including cell sources, encapsulation approaches, and implantation sites. This paper provides a comprehensive review of xenotransplantation of encapsulated pig islets for the treatment of type 1 diabetes mellitus, including current research findings and suggestions for future studies.

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Continuous and High-Level in Vivo Delivery of Endostatin from Recombinant Cells Encapsulated in TheraCyte® Immunoisolation Devices

Cited by 9 publications

References 22 publications

Insulin secretion of mixed insulinoma aggregates-gelatin hydrogel microspheres after subcutaneous transplantation

Insulin secretion of mixed insulinoma aggregates-gelatin hydrogel microspheres after subcutaneous transplantation

Anti-tumor therapy with macroencapsulated endostatin producer cells

Treatment of diabetes with encapsulated pig islets: an update on current developments

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