AVANTEA Laboratory of Reproductive Technologies

Cremona, Italy

AVANTEA Laboratory of Reproductive Technologies

Cremona, Italy
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Salama A.,University of Nantes | Salama A.,Societe DAcceleration du Transfert de Technologies Ouest Valorisation | Salama A.,Nantes University Hospital Center | Mosser M.,University of Nantes | And 48 more authors.
Diabetes | Year: 2017

Xenocell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type 1 diabetes for addressing organ shortage. In humans, however, natural and elicited antibodies specific for pig xenoantigens, a-(1,3)-galactose (GAL) and N-glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xenoislet rejection. We obtained double-knockout (DKO) pigs lacking GAL and Neu5Gc. Because Neu5Gc-/-mice exhibit glycemic dysregulations and pancreatic β-cell dysfunctions, we evaluated islet function and glucose metabolism regulation in DKO pigs. Isolation of islets from neonate piglets yielded identical islet equivalent quantities to quantities obtained from control wild-Type pigs. In contrast to wild-Type islets, DKO islets did not induce anti-Neu5Gc antibody when grafted in cytidine monophosphate-N-Acetylneuraminic acid hydroxylase KO mice and exhibited in vitro normal insulin secretion stimulated by glucose and theophylline. Adult DKO pancreata showed no histological abnormalities, and immunostaining of insulin and glucagon was similar to that from wild-Type pancreata. Blood glucose, insulin, C-peptide, the insulin-To-glucagon ratio, and HOMAinsulin resistance in fasted adult DKO pigs and blood glucose and C-peptide changes after intravenous glucose or insulin administration were similar to wild-Type pigs. This first evaluation of glucose homeostasis in DKO pigs for two major xenoantigens paves the way to their use in (pre)clinical studies. © 2017 by the American Diabetes Association.


PubMed | University of Padua, French Natural History Museum, AMaROC, University of Nantes and 2 more.
Type: | Journal: Diabetes | Year: 2017

Xeno-cell therapy from neonate or adult pig pancreatic islets is one of the most promising alternatives to allograft in type-1 diabetes for addressing organ-shortage. However, in human, natural and elicited antibodies specific for pig xenoantigens, (1,3)-galactose (GAL) and N-glycolylneuraminic acid (Neu5Gc), are likely to significantly contribute to xeno-islet rejection. We obtained double knockout pigs (DKO) lacking GAL and Neu5Gc. As Neu5Gc-/- mice exhibit glycemic dysregulations and pancreatic -cell dysfunctions, we evaluated islet function and glucose metabolism regulation in DKO pigs. Isolation of islets from neonate piglets yielded identical islet equivalent quantities (IEQs) to that obtained from control wild-type pigs. In contrast to wild-type islets, DKO islets did not induce anti-Neu5Gc antibody when grafted in CMAH-/- mice and exhibited in vitro normal insulin secretion stimulated by glucose and theophylline. Adult DKO pancreata showed no histological abnormalities and immunostaining of insulin and glucagon were similar to that from wild-types. Blood glucose, insulin, C-peptide, insulin:glucagon ratio and HOMA-IR in fasting adult DKO pigs, and blood glucose and C-peptide changes after I.V. glucose or insulin administration were similar to wild-types. This first evaluation of glucose homeostasis in DKO pigs for two major xenoantigens paves the way to their use in (pre)clinical studies.


Puglisi R.,Instituto Sperimentale Italiano Lazzaro Spallanzani | Pozzi A.,Instituto Sperimentale Italiano Lazzaro Spallanzani | Vanni R.,Instituto Sperimentale Italiano Lazzaro Spallanzani | Balduzzi D.,Instituto Sperimentale Italiano Lazzaro Spallanzani | And 7 more authors.
Asian Pacific Journal of Reproduction | Year: 2014

Objective: To investigate the telomere length in bovine offspring produced by a cloned and control bull, and the telomerase activity in embryos produced with the same technology. Methods: Five daughters of a control and five daughters of a bull cloned using a fibroblast of the control were produced by IVF using sperm of the two bulls. Blood samples of the offspring were collected at 2, 6, and 12 months of age and the relative telomere length (RTL) was assessed by flow cytometry. At same time the body growth, hematological profile, and clinical biochemistry of the same progeny was extensively surveyed, and results have been reported in a previous work. Thereafter, the telomerase activity was assessed using a real time PCR quantitative assay in groups of embryos produced with the same technology. Results: The offspring of the clone exhibited a modest, but significant (P<0.05), shortening of the telomeres (21.36%, 20.56% and 20.56%) compared to that of the control (23.78%, 23.53% and 22.43%) as mean values determined at 2, 6 and 12 months, respectively. Shortening of telomeres in respect to the age was not significant. No statistical difference was reported between telomerase activity assessed in 144 cloned (3.4-03 ± 2.4-03 amoles/μL) and 80 control (2.1-03 ± 1.8-03 amoles/μL) embryos. Conclusions: The results have revealed a moderate shortening of telomeres in the offspring of the clone with respect to control. However, this study did not evidence differences in the two progenies that suggest welfare problems during the first year of life. © 2014 Hainan Medical College.

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