Immunoisolation of Islets in High Guluronic Acid Barium‐Alginate Microcapsules Does Not Improve Graft Outcome at the Subcutaneous Site

Kerby, Alan; Bohman, Sara; Westberg, Helena; Jones, Peter M.; King, Aileen

doi:10.1111/j.1525-1594.2011.01411.x

Cited by 17 publications

(15 citation statements)

References 24 publications

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“…Encapsulation was performed as previously published . In brief, spheroids were washed in saline before being resuspended into a final 1.8% ultra‐pure low‐viscosity, high‐glucuronic acid (≥60%), sodium alginate (FMC BioPolymer, Drammen, Norway) solution, which was then delivered by syringe pump through a 0.2 mm diameter nozzle, from which droplets were electrostatically deposited into a divalent cationic solution (1 mM BaCl 2 + 50 mM CaCl 2 ) to cause gelation.…”

Section: Methodsmentioning

confidence: 99%

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Blackford

Segal

et al. 2018

Stem Cells Translational Medicine

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Recent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC‐Heps) afford tremendous possibilities for treatment of patients with liver disease. Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC‐Heps generated using a chemically defined four‐step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D poly(ethylene glycol)‐diacrylate fabricated inverted colloid crystal scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune‐privileged material alginate and remained viable as well as functional upon transplantation into immune competent mice. This is the first report we are aware of demonstrating cGMP‐compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications. stem cells translational medicine 2019;8:124&14

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Section: Methodsmentioning

confidence: 99%

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Blackford

Segal

et al. 2018

Stem Cells Translational Medicine

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show abstract

“…The transplant efficacy (requiring a marginal number of transplanted islets for glycemic control) of intramuscular and subcutaneous transplanted islets is worse than that of intraportally transplanted islets [40,41,58,[62][63][64][65][66]. This means that hypoxia might be a worse event for transplanted islets than some events in intraportal transplantation including IBMIR and specific immunity.…”

Section: Aspect Of Endocrine Function and Transplant Efficacymentioning

confidence: 99%

Strategy for clinical setting in intramuscular and subcutaneous islet transplantation

Sakata

Aoki

Yoshimatsu

et al. 2014

Diabetes Metabolism Res

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Intraportal islet transplantation has a long history as a procedure for clinical islet transplantation. However, many recent studies revealed that the intraportal procedure has some disadvantages in transplant efficiency and safety. Many candidates as an optimal transplant site for islets have been assessed, but further studies and clinical trials are still necessary. Intramuscular and subcutaneous spaces are important candidates, because the transplant and biopsy procedures are simple approaches with minimal invasion and few complications. Although they are sites with hypovascularity and hypoxia, which contribute to the poor transplant efficiency, many experimental trials for improving the outcome in intramuscular and subcutaneous islet transplantations have been performed, focusing on early angiogenesis and scaffolds for engrafting transplanted islets. We review current progress in intramuscular and subcutaneous islet transplantations and discuss ways to develop them as optimal transplant sites for islets.

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“…Encapsulation was performed as previously published [45,46]. In brief, spheroids were washed in saline before being re-suspended into a final 1.8% ultra-pure low-viscosity, highglucuronic acid (≥60%), sodium alginate (FMC BioPolymer, Drammen, Norway) solution, which was then delivered by syringe pump through a 0.2mm diameter nozzle, from which droplets were electrostatically deposited into a divalent cationic solution (1mM BaCl2 + 50mM CaCl2) to cause gelation.…”

Section: Alginate Encapsulation Of Hpsc-derived Hepatocyte Spheroidsmentioning

confidence: 99%

Validation of a library of cGMP-compliant human pluripotent stem cell lines for use in liver therapy

Blackford

Segal

et al. 2018

Preprint

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DisclaimersThe authors declare that there is no conflict of interest regarding the publication of this article Acknowledgments of Grants SJIB is supported by a GSTT BRC PhD award STR is supported by an MRC Clinician Scientist Award (MGSBACR) AbstractRecent advancements in the production of hepatocytes from human pluripotent stem cells (hPSC-Heps) afford tremendous possibilities for treatment of patients with liver disease.Validated current good manufacturing practice (cGMP) lines are an essential prerequisite for such applications but have only recently been established. Whether such cGMP lines are capable of hepatic differentiation is not known. To address this knowledge gap, we examined the proficiency of three recently derived cGMP lines (two hiPSC and one hESC) to differentiate into hepatocytes and their suitability for therapy. hPSC-Heps generated using a chemically defined four-step hepatic differentiation protocol uniformly demonstrated highly reproducible phenotypes and functionality. Seeding into a 3D PEG-DA fabricated inverted colloid crystal (ICC) scaffold converted these immature progenitors into more advanced hepatic tissue structures. Hepatic constructs could also be successfully encapsulated into the immune-privileged material alginate. This is the first report we are aware of demonstrating cGMP-compliant hPSCs can generate cells with advanced hepatic function potentially suitable for future therapeutic applications.

show abstract

Immunoisolation of Islets in High Guluronic Acid Barium‐Alginate Microcapsules Does Not Improve Graft Outcome at the Subcutaneous Site

Cited by 17 publications

References 24 publications

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Validation of Current Good Manufacturing Practice Compliant Human Pluripotent Stem Cell-Derived Hepatocytes for Cell-Based Therapy

Strategy for clinical setting in intramuscular and subcutaneous islet transplantation

Validation of a library of cGMP-compliant human pluripotent stem cell lines for use in liver therapy

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