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Biomedical subjects

R B Elliott

Publications and source records attributed to R B Elliott.

134 records · Page 8Linked to original sources
PubMedDate not supplied

Xenotransplantation of neonatal porcine liver cells.

Xenotransplantation of porcine liver cell types may provide a means of overcoming the shortage of suitable donor tissues to treat hepatic diseases characterized by inherited inborn errors of metabolism or protein production. Here we report the successful isolation, culture, and xenotransplantation of liver cells harvested from 7- to 10-day-old piglets. Liver cells were isolated and cultured immediately after harvesting. Cell viability was excellent (>90%) over the duration of the in vitro studies (3 weeks) and the cultured cells continued to significantly proliferate. These cells also retained their normal secretory and metabolic capabilities as determined by continued release of albumin, factor 8, and indocyanin green (ICG) uptake. After 3 weeks in culture, porcine liver cells were loaded into immunoisolatory macro devices (Theracyte devices) and placed into the intraperitoneal cavity of immunocompetant CD1 mice. Eight weeks later, the devices were retrieved and the cells analyzed for posttransplant determinations of survival and function. Post mortem analysis confirmed that the cell-loaded devices were biocompatible, and were well-tolerated without inducing any notable inflammatory reaction in the tissues immediately surrounding the encapsulated cells. Finally, the encapsulated liver cells remained viable and functional as determined by histologic analyses and ICG uptake/release. The successful harvesting, culturing, and xenotransplantation of functional neonatal pig liver cells support the continued development of this approach for treating a range of currently undertreated or intractable hepatic diseases.

Animals↗
PubMedDate not supplied

Transplantation of micro- and macroencapsulated piglet islets into mice and monkeys.

Neonatal porcine islets within alginate microcapsules transplanted intraperitoneally (IP) or within semi-permeable macrocapsules (TheraCyte) and transplanted subcutaneously (SC) survive and reverse diabetes for up to 16 weeks in diabetic autoimmune nonobese diabetic (NOD) mice. The islets in microcapsules transplanted IP into nondiabetic cynomolgus monkeys survived for 8 weeks. Similar results were shown with islets transplanted in TheraCytes. Neither species showed adverse effects or evidence of infection with porcine endogenous retroviruses or other endemic pig viruses. Proof of principle is illustrated for successful xenotransplantation in humans.

Animals↗
PubMedDate not supplied

Identification of pig circovirus type 2 in New Zealand pigs.

Interest in porcine circovirus has been stimulated by the recent emergence of postweaning multisystemic wasting syndrome (PMWS) in pigs and the potential use of pig organs for xenotransplantation in humans. Porcine circovirus type 1 (PCV1) is considered to be widespread in pigs but nonpathogenic. Circovirus type 2 (PCV2) is a similar virus but has been differentiated only recently as a separate type. High tissue concentrations of PCV2 are associated with lesions in PMWS cases, but the etiological role of this agent in the disease remains unclear. The presence of PCV1 in New Zealand pigs has been previously reported based on serological data. PMWS has been recently recorded in New Zealand pigs. The epidemiology of PCV2 in New Zealand pigs has not been examined. The purpose of the study was to look for evidence of circoviruses in New Zealand pig herds. Pig circovirus DNA was sought in various tissues using the polymerase chain reaction. Circovirus type 2 was found in New Zealand pig herds, without any evidence that PMWS has ever occurred in these herds. Newborn piglets were shown to have infection, suggesting vertical transmission of the virus.

Aging↗
PubMedDate not supplied

No evidence of infection with porcine endogenous retrovirus in recipients of encapsulated porcine islet xenografts.

Transplantation of pig tissues into humans has the potential for cotransferring pig infections. Knowledge of the epidemiology of pig infections transmissible to humans allows the development of risk limitation strategies at the source herd level, but potentially infectious pig endogenous retrovirus (PERV) is ubiquitous in all domestic pigs and therefore is not avoidable. Using a specific and sensitive RT-PCR and nested PCR for PERV nucleic acids with primers, the screening of pigs from New Zealand herds for the presence and expression of the PERV was conducted. The presence of PERV proviral DNA (pol and env region) and viral RNA was demonstrated in all tested pig tissues including pancreas, liver, spleen, brain, heart, and PBMC. Using the same assays it was established that different tissues (liver, spleen, and heart) of nude and nonobese diabetic (NOD) mice previously transplanted with nonencapsulated pig islets were PERV DNA and RNA negative. Alginate polylysine capsules prepared with encapsulated pig islets were tested for possible leakage of viral particles or viral nucleic acids. RNA was extracted from the supernatant of viable encapsulated pig islet cells grown in culture for 2 months. No evidence of PERV RNA or of cellular nucleic acids could be found. Two adult type I diabetic subjects were transplanted with 1 x 10(6) neonatal pig islets encased in alginate capsules into the peritoneal cavity. One patient was immunosuppressed. Both showed evidence of graft function (up to 34% reduction in insulin dose, corresponding increase in serum pig C-peptide) for up to 2 years. DNA and RNA were extracted from PBMC and blood plasma of both patients at 19 months posttransplant. No evidence of PERV proviral DNA or RNA could be detected. Piglet islets contain PERV DNA and RNA, but this does not traverse the capsules used or produce any evidence of infection in nude and nonobese diabetic (NOD) mice or humans.

Adult↗
PubMedDate not supplied

A population based strategy to prevent insulin-dependent diabetes using nicotinamide.

It has been postulated that treatment with nicotinamide may prevent or delay the onset of insulin dependent diabetes mellitus. We report the findings of a population based diabetes prevention trial which tests this hypothesis. 33,658 school children aged 5-7.9 years were randomly selected (by school) from a total population of 81,993 of such children in the Auckland (New Zealand) region. They were offered testing for islet cell antibodies. 20,195 (60%) consented to testing. Of these 185 had islet cell antibodies and met the criteria for treatment with nicotinamide. 173 received this treatment. The study population has an average follow up time of 7.1 years. The diabetes incidence of the untested controls was: 16.07 (12.4-20.5 95% CI) /100,000 person years at risk; in the group who were tested and treated when deemed appropriate: 7.14 (3.1-14.1 95% CI); and in the group offered testing but who did not consent ("refusers'): 18.48 (10.1-31.0 95% CI). The tested group had a rate of diabetes of 41% (20-85 95% CI) of the other groups combined after an age adjustment, which is significant (p = 0.008). The tested group combined with the "refuser' group (i.e. "intention to treat') also has a lower incidence than the control group (p = 0.12). Nicotinamide has a protective effect against the development of insulin dependent diabetes in this setting but the size of the effect has a wide confidence interval. Further follow up may define the magnitude of the protective effect within narrower limits.

Autoantibodies↗