A Continuously Oxygenated Macroencapsulation System Enables High-Density Packing and Delivery of Insulin-Secreting Cells

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The paper studies an implantable immuno-protective cell encapsulation system for insulin-secreting cells, focusing on overcoming low oxygen tension that limits cell survival, function, and packing density. Using a miniaturized electrochemical oxygen generator that uses electrolysis of tissue moisture to provide continuous oxygen, the authors tested oxygen generation control and evaluated viability/function of insulinoma aggregates and human pancreatic islets in vitro under 1% O2. They report that the continuously oxygenated system maintained viability and function at high densities (60,000 IEQ/mL) under hypoxic culture, and in an allogeneic rat subcutaneous model it reversed diabetes for up to ~3 months without immunosuppression, whereas non-oxygenated implants did not; a major stated limitation is the lack of long-term efficacy beyond this window. This paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

The encapsulation of insulin-secreting cells within immuno-protective systems holds significant promise for curative treatment of type 1 diabetes without immunosuppression. A major challenge, however, remains the inadequate oxygen tension within the encapsulation systems, which compromises the survival and function of encapsulated cells and necessitates low packing density and impractically large systems to deliver a curative cell mass. In this study, we present a novel cell encapsulation system capable of generating oxygen via the electrolysis of tissue moisture to provide a continuous oxygen supply to densely packed insulin-secreting cells. Our system comprises a miniaturized implantable electrochemical oxygen generator (iEOG) and a scalable cylindrical cell encapsulation pouch, designed in a linear configuration to facilitate minimally invasive implantation and retrieval. The oxygen generation from the system was shown to be precisely controlled, stable, and capable of supporting clinically relevant doses of pancreatic islets. In vitro studies demonstrated that the oxygenated system effectively maintained the viability and function of insulinoma cell aggregates and human pancreatic islets at densities of 60,000 islet equivalents per mL (IEQ/mL) or 4,200 IEQ/cm² under a hypoxic cell culture condition (1% O ). In an allogeneic rat model, the oxygenated systems containing pancreatic islets implanted into the poorly vascularized but clinically attractive subcutaneous space at a density of 60,000 IEQ/mL successfully reversed diabetes for up to about 3 months without the need for immunosuppression, while animals implanted with non-oxygenated systems remained diabetic. Most (∼ 90%) of the pancreatic islets encapsulated in the continuously oxygenated systems were found viable and functional upon retrieval. These findings suggest the feasibility of using continuous oxygenation to support insulin-secreting cells at high loading densities in subcutaneous space, enabling the development of an encapsulation system with clinically practical dimensions.
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Abstract The encapsulation of insulin-secreting cells within immuno-protective systems holds significant promise for curative treatment of type 1 diabetes without immunosuppression. A major challenge, however, remains the inadequate oxygen tension within the encapsulation systems, which compromises the survival and function of encapsulated cells and necessitates low packing density and impractically large systems to deliver a curative cell mass. In this study, we present a novel cell encapsulation system capable of generating oxygen via the electrolysis of tissue moisture to provide a continuous oxygen supply to densely packed insulin-secreting cells. Our system comprises a miniaturized implantable electrochemical oxygen generator (iEOG) and a scalable cylindrical cell encapsulation pouch, designed in a linear configuration to facilitate minimally invasive implantation and retrieval. The oxygen generation from the system was shown to be precisely controlled, stable, and capable of supporting clinically relevant doses of pancreatic islets. In vitro studies demonstrated that the oxygenated system effectively maintained the viability and function of insulinoma cell aggregates and human pancreatic islets at densities of 60,000 islet equivalents per mL (IEQ/mL) or 4,200 IEQ/cm² under a hypoxic cell culture condition (1% O ). In an allogeneic rat model, the oxygenated systems containing pancreatic islets implanted into the poorly vascularized but clinically attractive subcutaneous space at a density of 60,000 IEQ/mL successfully reversed diabetes for up to about 3 months without the need for immunosuppression, while animals implanted with non-oxygenated systems remained diabetic. Most (∼ 90%) of the pancreatic islets encapsulated in the continuously oxygenated systems were found viable and functional upon retrieval. These findings suggest the feasibility of using continuous oxygenation to support insulin-secreting cells at high loading densities in subcutaneous space, enabling the development of an encapsulation system with clinically practical dimensions. Competing Interest Statement Tung T. Pham, Phuong L. Tran, Linda Tempelman, James A. Flanders, Simon Stone and Minglin Ma are inventors of the technology described in this paper. Tung T. Pham and Simon G. Stone are advisors; Linda Tempelman, James A. Flanders and Minglin Ma are co-founders of Persista Bio Inc, a company formed to commercialize the technology.

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