Embryonic pig pancreatic tissue for the treatment of diabetes in a nonhuman primate model.

Xenotransplantation of pig tissues has great potential to overcome the shortage of organ donors. One approach to address the vigorous immune rejection associated with xenotransplants is the use of embryonic precursor tissue, which induces and utilizes host vasculature upon its growth and development. Recently, we showed in mice that embryonic pig pancreatic tissue from embryonic day 42 (E42) exhibits optimal properties as a beta cell replacement therapy. We now demonstrate the proof of concept in 2 diabetic Cynomolgus monkeys, followed for 393 and 280 days, respectively. A marked reduction of exogenous insulin requirement was noted by the fourth month after transplantation, reaching complete independence from exogenous insulin during the fifth month after transplantation, with full physiological control of blood glucose levels. The porcine origin of insulin was documented by a radioimmunoassay specific for porcine C-peptide. Furthermore, the growing tissue was found to be predominantly vascularized with host blood vessels, thereby evading hyperacute or acute rejection, which could potentially be mediated by preexisting anti-pig antibodies. Durable graft protection was achieved, and most of the late complications could be attributed to the immunosuppressive protocol. While fine tuning of immune suppression, tissue dose, and implantation techniques are still required, our results demonstrate that porcine E-42 embryonic pancreatic tissue can normalize blood glucose levels in primates. Its long-term proliferative capacity, its revascularization by host endothelium, and its reduced immunogenicity, strongly suggest that this approach could offer an attractive replacement therapy for diabetes.

Thrombophilia in infancy: factor V Leiden and MTHFR or factor II double heterozygocity as a risk factor.

Thrombophilic risk factors are associated with thromboembolism in children but data in infants and neonates are not well established. The authors report a series of 9 infants with thrombotic events and the associated genetic risk factors. The clinical and laboratory records of newborns and infants with a history of thrombotic events were summarized, while patients with underlying diseases were excluded. The frequency of the genetic mutations was compared to a control group of 80 children from the same ethnic origin. In 6 patients a cerebrovascular accident was diagnosed and in 3 newborns, CT scan could diagnose antenatal brain infarct. In another 2 patients deep-vein thrombosis associated with femoral catheterization was diagnosed. Seven infants were factor V Leiden heterozygous and another one homozygous. Methylenetetrahydrofolate reductase genotype was found in 5 infants. Five cases were found to be double heterozygous for those two mutations, and another one double heterozygous for FVL and factor II. The results of this small series of patients indicate that cerebrovascular accident is the major thrombotic event in infants and the combination of more than one prothrombotic factors may be the cause of those events. The correct management, including anticoagulant therapy, is still under discussion and waiting for larger series and long-term follow-up results until accurate recommendations can be made.