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Evidence of safety and efficacy of two forms of neonatal cell transplants
Author(s) -
Elliott Robert B.,
Nathu Divya
Publication year - 2013
Publication title -
xenotransplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.052
H-Index - 61
eISSN - 1399-3089
pISSN - 0908-665X
DOI - 10.1111/xen.12014_7
Subject(s) - xenotransplantation , medicine , herd , islet , glucagon , insulin , transplantation , veterinary medicine
On behalf of DOL and LCT A clinical trial in 14 adult type 1 diabetics intra‐peritoneal alginate microencapsulated neonatal porcine islets transplants commenced in NZ over 2 years ago and the last patient has just completed the required 12 months of follow up. To meet regulatory requirements for xenotransplantation, an elaborate program on xenovirology has been developed on one unique herd of pigs that was free from all conventional pathogens and was qualified as “null” pigs, i.e. they do not have a transmittable pig endogenous retrovirus (PERV). These pigs are the animal founders for the DPF donor herd. A comprehensive program for patients’ microbiology follow‐up was also developed. This program includes assays developed for monitoring potential infection with PERV and other potentially xenotic pathogens. All of the patients selected had unaware hypoglycaemia. The dose of islets used varied from 5000/kg (n = 4) 10 000/kg (n = 4) 15 000/kg (n = 4), and 20 000/kg (n = 2). The patients experience little if any side effects and there was no evidence of xenosis. Unaware hypoglycaemia was lessened in all groups but more so in the 10 000/kg group. Insulin dose was lowered and HbA1c improved in some but not all subjects. The patients with maximum insulin dose drop received 5000/kg dose. There was no clear cut relationship of return of hypoglycaemia awareness and glucagon or adrenergic responses to induced hypoglycaemia. There was direct laboratory evidence of islet beta cell function. Clinical follow up at 2 years of some patients indicates persistence of the benefits. A further clinical trial involving a different dosing schedule and some technical improvements is in progress. Choroid plexus (CP) ependymal epithelium secretes a wide variety of neurotrophic and neural support molecules. Micro‐encapsulated CP delivered intra‐cerebrally into rat models of stroke, Huntington's disease and Parkinson's disease show remarkable functional and histological recovery. In the quinolinic acid primate model of Huntington's and the MTPP model of Parkinson's functional recovery and relevant histological evidence of neuro‐regeneration were seen. The treatment was safe. A clinical trial of this form of treatment in humans with Parkinson's is being undertaken. Conclusions: Xenotransplantation of microencapsulated islets and other cell types into human and non‐human primates from a biocertified herd of pigs prepared under GMP conditions can be conducted with safety and efficacy. Further improvements in clinical outcomes are expected with technical advances.