Initial Clinical Evaluation of VC-01TM Combination Product—A Stem Cell–Derived Islet Replacement for Type 1 Diabetes (T1D)

Henry, Robert R.; Pettus, Jeremy; Wilensky, Jon; Shapiro, A. M. James; Senior, Peter; Roep, Bart O.; Wang, Thomas J.; Kroon, Evert; Scott, Michael M.; D’Amour, Kevin A.; Foyt, Howard L.

doi:10.2337/db18-138-or

Cited by 73 publications

(56 citation statements)

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“…Secondly, the devices elicit a giant cell foreign body reaction which appears to be associated with a deleterious effect on the survival of implanted cells (oral presentation: Henry et al . ).…”

Section: How Are Stem Cells Being Applied In Current Clinical Trials?mentioning

confidence: 97%

“…Preliminary reports from initial clinical trials suggest that the macroencapsulation device has been successful at containing implanted cells and preventing immunization of the host [28]; however, two major challenges have been identified. Firstly, cell survival has been highly variable in explanted sentinel units, with the majority showing very few, if any, surviving cells.…”

Section: Biocompatabilitymentioning

confidence: 99%

“…Whether this is attributable to hypoxia in the early period after implantation or other factors is not known because explanted units demonstrated vascularization adjacent to the membrane. Secondly, the devices elicit a giant cell foreign body reaction which appears to be associated with a deleterious effect on the survival of implanted cells (oral presentation: Henry et al [28]).…”

Section: Biocompatabilitymentioning

confidence: 99%

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Stem cell therapies for Type 1 diabetes: current status and proposed road map to guide successful clinical trials

Senior

Pettus

2018

Diabet. Med.

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Many people with Type 1 diabetes struggle with the burden of self‐management and are unable to achieve optimal glycaemic control without risk of hypoglycaemia. Future therapies with the potential to reduce the risk for short‐ and long‐term complications while simultaneously reducing the burden of diabetes are therefore attractive. β‐cell replacement is one strategy which might achieve this. Islet transplantation is limited by organ supply and the risks of long‐term immunosuppression. Encapsulated stem‐cell‐derived β cells have the potential to address both of these issues and phase I/II clinical trials of encapsulated pancreatic progenitors have begun. A significant risk associated with the translation of stem‐cell science to the clinical management of Type 1 diabetes is an underestimation of the complexity of the process and a mismatch between the hype and the expectations of both people with Type 1 diabetes and the public. We provide an update on progress in clinical trials of encapsulated stem‐cell‐derived β cells and propose a road map for the design and conduct of future trials to facilitate the translation of this exciting science to clinical care.

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Section: How Are Stem Cells Being Applied In Current Clinical Trials?mentioning

confidence: 97%

Section: Biocompatabilitymentioning

confidence: 99%

Section: Biocompatabilitymentioning

confidence: 99%

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Stem cell therapies for Type 1 diabetes: current status and proposed road map to guide successful clinical trials

Senior

Pettus

2018

Diabet. Med.

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“…Recently, ViaCyte performed clinical trials using PECs encapsulated in the Encaptra® Drug Delivery System [105]. However, foreign body reaction hasbeen reported as a limiting factor for the engraftment of encapsulated cells [106].…”

Section: Challenges and Perspectives Of Insulin‐secreting Organoidsmentioning

confidence: 99%

Generation of insulin‐secreting organoids: a step toward engineering and transplanting the bioartificial pancreas

et al. 2020

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Summary Diabetes is a major health issue of increasing prevalence. ß‐cell replacement, by pancreas or islet transplantation, is the only long‐term curative option for patients with insulin‐dependent diabetes. Despite good functional results, pancreas transplantation remains a major surgery with potentially severe complications. Islet transplantation is a minimally invasive alternative that can widen the indications in view of its lower morbidity. However, the islet isolation procedure disrupts their vasculature and connection to the surrounding extracellular matrix, exposing them to ischemia and anoikis. Implanted islets are also the target of innate and adaptive immune attacks, thus preventing robust engraftment and prolonged full function. Generation of organoids, defined as functional 3D structures assembled with cell types from different sources, is a strategy increasingly used in regenerative medicine for tissue replacement or repair, in a variety of inflammatory or degenerative disorders. Applied to ß‐cell replacement, it offers the possibility to control the size and composition of islet‐like structures (pseudo‐islets), and to include cells with anti‐inflammatory or immunomodulatory properties. In this review, we will present approaches to generate islet cell organoids and discuss how these strategies can be applied to the generation of a bioartificial pancreas for the treatment of type 1 diabetes.

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“…Fibrotic growth along with immune cells around device as well as amyloid formation was reported for βAir device [12]. Low levels of engraftment of encapsulated cells due to foreign body reaction were reported for Viacyte's STEP ONE clinical trial [13].…”

Section: Introductionmentioning

confidence: 99%

Development of Nanoporous Polyurethane Hydrogel Membranes for Cell Encapsulation

Garle

Miller

Sarrafian

et al. 2019

Regen. Eng. Transl. Med.

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Cell encapsulation for treatment of diseases like type 1 diabetes (T1D) has great potential when used in combination with development of insulin responsive beta cells. However, for translation of this therapy into clinical practice, there is a need for suitable encapsulation devices. Here, we report development of polyurethane-zwitterionic acrylate double network-based membranes for macro device-based cell encapsulation. Polyurethane hydrogels with 60 to 90% water content (WC) were evaluated for permeability and hydrogels with 80 and 90% WC were found to have highest permeability. Structural characterization of these hydrogels' samples prepared cryogenically by scanning electron microscopy (cryo-SEM) revealed that 90% WC hydrogels were nanoporous with large interconnected pores. Tuning of porosity and structure was achieved by blending of hydrogels with varying WC resulting in pores of~200 nm size. These membranes supported viability of encapsulated cells after removal of cytotoxic leachables by ethanol treatment. Double network formation was performed by UV polymerization and incorporation of zwitterionic groups was confirmed by ATR and WC of hydrogels. Varying of zwitterion type is allowed for tuning of WC of hydrogels. Gene expression of RAW 264.7 macrophages on exposure to the hydrogels found the zwitterionic double network hydrogels to be less stimulating than the bare hydrogel. To determine translational potential of the hydrogel, sterilization of the hydrogels using supercritical carbon dioxide was evaluated. Survivor enumeration testing revealed that the kill rate for the process~1 log 10 per 8 min and 2-h treatment is sufficient for sterility assurance level (SAL) of 10 −6. Thus, we have developed hydrogel polyurethane membranes suitable for cell encapsulation in macro devices. Lay Summary We want to develop a device for cell encapsulation which is needed for treating diseases like T1D. In these devices, cells will be loaded and implanted in the body. These encapsulated cell secretions would provide the function of various endocrine organs. We have developed a hydrogel-based nanoporous membrane which would hold the cells and allow for exchange of nutrients and cell secretions. Future Studies After the development of membrane, future studies will focus on evaluating the immune response to the hydrogel as well as long term delivery of immune modulatory drugs to prevent fibrosis. Various drug encapsulation and delivery designs will be evaluated for controlled localized delivery of the drugs. The optimum combination would then be combined with the hydrogels device and test their efficacy in regulating cell viability and immune response in animal models.

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Initial Clinical Evaluation of VC-01TM Combination Product—A Stem Cell–Derived Islet Replacement for Type 1 Diabetes (T1D)

Cited by 73 publications

References 0 publications

Stem cell therapies for Type 1 diabetes: current status and proposed road map to guide successful clinical trials

Stem cell therapies for Type 1 diabetes: current status and proposed road map to guide successful clinical trials

Generation of insulin‐secreting organoids: a step toward engineering and transplanting the bioartificial pancreas

Development of Nanoporous Polyurethane Hydrogel Membranes for Cell Encapsulation

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