Real-time assessment of encapsulated neonatal porcine islets prior to clinical xenotransplantation
| Autor: | Kate R. Mueller, Klearchos K. Papas, Lee Law, Avik Shome, Henk Jan Schuurman, Jennifer P. Kitzmann, Robert B. Elliott, Marija Muzina |
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| Rok vydání: | 2012 |
| Předmět: |
Transplantation
geography medicine.medical_specialty Type 1 diabetes geography.geographical_feature_category business.industry Xenotransplantation medicine.medical_treatment Porcine islets Immunology Standard methods Islet medicine.disease Surgery Cell therapy Andrology Diabetes mellitus medicine business |
| Zdroj: | Xenotransplantation. 19:333-336 |
| ISSN: | 0908-665X |
| Popis: | Clinical islet transplantation using human pancreasdonors in patients with type 1 diabetes mellitus isan established cellular therapy, primarily, for thosepatients who suffer from severe hypoglycemicunawareness [1]. However, the low availability ofpancreata that are suitable for islet manufacturingand the variability in isolated human islet qualityhinders this treatment from becoming broadlyapplicable to meet the medical need. NeonatalKitzmann JP, Law L, Shome A, Muzina M, Elliott RB, Mueller KR,Schuurman H-J, Papas KK. Real-time assessment of encapsulatedneonatal porcine islets prior to clinical xenotransplantation.Xenotransplantation 2012; 19: 333–336. 2012 John Wiley & Sons A/S.Abstract: Background: Porcine islet transplantation is emerging as anattractive option for the treatment of patients with type 1 diabetes, withthe possibility of providing islets of higher and more consistent qualityand in larger volumes than available from human pancreata. The use ofencapsulated neonatal porcine islets (ENPI) is appealing because it canaddress islet supply limitations while reducing the need for anti-rejectiontherapy. Pre-transplant characterization of ENPI viability and potencyis an essential component of the production process. We applied thevalidated assay for oxygen consumption rate normalized for DNAcontent (OCR/DNA) to characterize ENPI viability.Methods: ENPI of low viscosity and high m alginate were preparedaccording to standard methods and characterized at various culture timepoints up to 5 weeks.Results: The OCR/DNA (nmol/minAEmgDNA ± SEM) of ENPI(235 ± 10, n = 9) was comparable to that of free NPI (255 ± 14,n = 13). After encapsulation, NPI OCR/DNA was sustained over aculture period of up to 5 weeks. The average OCR/DNA of ENPIcultured longer than 9 days was higher than that of freshly encapsulatedNPI.Conclusion: This is the first characterization of ENPI by a validated andmore sensitive method for product viability. The NPI encapsulationprocess does not compromise viability as measured by OCR/DNA, andENPI can be cultured for up to 5 weeks with maintenance of viability.ENPI meet or exceed current adult porcine islet product release criteria(established at the University of Minnesota) for preclinical xenotrans-plantation in terms of OCR/DNA. |
| Databáze: | OpenAIRE |
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