Effects of Simulated Microgravity on the Morphology and Function of Neonatal Porcine Cell Clusters Cultured With and Without Sertoli Cells
Abstract:Human islet allografts are well known to induce full and sustained remission of hyperglycemia, with complete normalization of key metabolic parameters. Nevertheless, acquiring human islets, even from cadaveric human donor pancreases, remains a significant impediment to successful transplantation therapy for diabetes. To overcome this difficulty, neonatal porcine cell clusters (NPCCs) have been considered for human islet substitutes because they are easily obtained by collagenase digestion of the neonatal piglet pancreas. Currently, the major hurdle in using NPCCs for xenograft is the delay (time lag) in achieving the posttransplant normalization of blood glucose levels in animal diabetic recipients. The present work is the first attempt to evaluate whether incubation of NPCCs in simulated microgravity, in the presence or absence of Sertoli cells (SC), may reduce the maturation time lag of -cells by differentiation acceleration in vitro, thereby expediting production, viability, and acquisition of functional competence of pretransplantation -cell-enriched islets. Following a 3-day incubation period, NPCCs maintained in conventional culture, NPCCs incubated in simulated microgravity in the HARV biochamber, and NPCCs plus co-incubated SC in simulated microgravity were examined for viability, morphology, and insulin secretion. Results show that NPCCs grown alone in the HARV biochamber are superior in quality, both in terms of viability and functional competence, when compared to other culture pretreatment protocols. This finding strongly suggests that NPCC pretreatment in simulated microgravity may enhance the transplantation success of NPCCs in the diabetic recipient.
Document Type: Research Article
Affiliations: 1: *Department of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy 2: †Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy 3: Department of Chemistry and Technology of the Drugs, School of Pharmacy, University of Perugia, Perugia, Italy 4: Department of Internal Medicine and Endocrine and Metabolic Sciences, University of Perugia, Perugia, Italy 5: Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy 6: Department of Morphology and Embriology, Section of Human Anatomy, University of Ferrara, Ferrara, Italy 7: Department of Anatomy, University of South Florida College of Medicine, Tampa, FL, USA
Publication date: January 1, 2006
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