Accelerated Functional Maturation of Isolated Neonatal Porcine Cell Clusters: In Vitro and In Vivo Results in NOD Mice
Abstract:Neonatal porcine cell clusters (NPCCs) might replace human for transplant in patients with type 1 diabetes mellitus (T1DM). However, these islets are not immediately functional, due to their incomplete maturation/differentiation. We then have addressed: 1) to assess whether in vitro coculture of islets with homologous Sertoli cells (SC) would shorten NPCCs' functional time lag, by accelerating the -cell biological maturation/differentiation; 2) to evaluate metabolic outcome of the SC preincubated, and microencapsulated NPCCs, upon graft into spontaneously diabetic NOD mice. The islets, isolated from <3 day piglets, were examined in terms of morphology/viability/function and final yield. SC effects on the islet maturation pathways, both in vitro and in vivo, upon microencapsulation in alginate/poly-L-ornithine, and intraperitoneal graft into spontaneously diabetic NOD mice were determined. Double fluorescence immunolabeling showed increase in -cell mass for SC+ neonatal porcine islets versus islets alone. In vitro insulin release in response to glucose, as well as mRNA insulin expression, were significantly higher for SC+ neonatal porcine islets compared with control, thereby confirming SC-induced increase in viable and functional -cell mass. Graft of microencapsulated SC+ neonatal porcine islets versus encapsulated islets alone resulted in significantly longer remission of hyperglycemia in NOD mice. We have preliminarily shown that the in vitro NPCCs' maturation time lag can dramatically be curtailed by coincubating these islets with SC. Graft of microencapsulated neonatal porcine islets, precultured in Sertoli cells, has been proven successful in correcting hyperglycemia in stringent animal model of spontaneous diabetes.
Document Type: Review Article
Affiliations: 1: Department of Internal Medicine (Di.M.I.), Section of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Via E. Dal Pozzo, Perugia 06126, Italy 2: Department of Chemistry and Technology of the Drugs, Faculty of Pharmacy, University of Perugia, Via del Liceo 1, Perugia 06123, Italy 3: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Via del Giochetto, Perugia 06123, Italy 4: Department of Morphology and Embryology, Section of Human Anatomy, University of Ferrara, Via Fossato di Mortara 66, Ferrara 44100, Italy
Publication date: May 1, 2005
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