Abstract

Shortage in human donor pancreases has raised the need to develop alternative sources for beta cell replacement therapy in type 1 diabetes. The potential to meet clinical demand with porcine pancreases has led to laboratory testing of their islet cell implants as generated from adult, neonatal and fetal organs. Both free and encapsulated porcine cell preparations have been shown to establish insulin-producing implants in animal models, but little is known about the functional properties of their beta cells with time, in particular in comparison with those of human beta cells. We have conducted such comparison for alginate-encapsulated implants of porcine pancreatic endocrine cells that were purified from prenatal organs (110 days gestation, encapsulated cells manufactured by Beta-Cell NV, Belgium and provided by Dr S. Notebaert) and administered subcutaneously in normal immune-deficient NOD/scid mice. Injection of preparations with 4 x 105 beta cells resulted in detectable plasma porcine C-peptide levels (> 0.1 ng/ml) at PT week 1, increasing time-dependently to > 3 ng/ml at PT week 10 and beyond. At PT week 20, the secretory activity of the porcine beta cell implant had suppressed that of the mouse pancreas. Retrieved capsules contained over 3-fold more beta cells than at start, while alpha cell number was 50% lower; consequently their alpha over beta cell ratio was reduced by 70 percent. Their beta cells exhibited a 4-fold higher insulin content than at start; it was also significantly higher than that in adult human pancreatic islet cell isolates. They exhibited a glucose-inducible insulin biosynthetic activity comparable to that in adult human islets. Their insulin secretory activity responded equally rapidly to glucose stimulation, but the amplitude was significantly lower. It is concluded that porcine pancreatic endocrine cells purified from prenatal organs can establish a sustained functional beta cell mass when implanted as microcapsules in the subcutis. Analysis of retrieved implants for their beta cell number and beta cell properties is indicative for a marked functional capacity and reserve, that stands the comparison with clinical-grade human islet cell preparations.
Original languageEnglish
Publication statusPublished - Sep 2016
EventEASD Islet Study Group -
Duration: 16 Sep 201618 Sep 2016

Conference

ConferenceEASD Islet Study Group
Period16/09/1618/09/16

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  • EASD Islet Study Group

    Thomas Robert (Participant)

    16 Sep 201618 Sep 2018

    Activity: Participating in or organising an eventParticipation in conference

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