Real‐time assessment of encapsulated neonatal porcine islets prior to clinical xenotransplantation

Abstract

This is the first characterization of ENPI by a validated and more sensitive method for product viability. The NPI encapsulation process does not compromise viability as measured by OCR/DNA, and ENPI 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 xenotransplantation in terms of OCR/DNA.

Alginate Microencapsulation of Human Islets Does Not Increase Susceptibility to Acute Hypoxia

“…It is thus a positive finding (in terms of the clinical utility of encapsulated islets) that oxygen consumption under basic conditions (no hypoxia) was not diminished in encapsulated islets (Figure 2). These findings are in line with those reported previously for pig islets encapsulated in a monolayer cellular device [15] and for microencapsulated neonatal porcine islets [14]. The recorded values of oxygen flux (pmol/s/mill cells) in our study are comparable to the findings for rat islets by use of the same type of oxygraph [29].…”

“…A negative impact of the—inevitable—hypoxia during the immediate period following transplantation could possibly be worsened by encapsulation, since the distance of diffusion for oxygen could be greater in encapsulated versus nonencapsulated islets (or amassed beta cells) [11, 12], and a negative effect of clustering of islets may occur [13]. Comparisons of oxygen uptake in encapsulated versus nonencapsulated islets have been done for neonatal porcine [14] and pig [15] islets in vitro (normoxic conditions) without unveiling negative effects of encapsulation, while encapsulation of rat islets led to a significant reduction of oxygen uptake [16]. However, a similar comparison has, to the best of our knowledge, not been made for human islets, neither in a setting of normoxic nor hypoxic culture conditions.…”

Islet xenotransplantation: what is the optimal age of the islet‐source pig?

“…Is there any published evidence suggesting that this age is optimal? Most studies of pig NICC transplantation into mice have used donors of 1 to 7 days of age .…”

Xenotransplantation literature update, January–February 2013

“…In a Brief Communication, Kitzmann et al. measured the oxygen consumption rate normalized for DNA content (OCR/DNA) to characterize the viability of encapsulated NPI prepared by Living Cell Technologies, which have been approved for clinical trials. The mean OCR/DNA value of encapsulated NPI was 235 nmol/min/mg DNA, comparable to that of free NPI and sustained over a culture period of up to 5 weeks.…”