Myocardial implantation of a combination stem cell product by using a transendocardial MYOSTAR injection catheter: A technical assessment.

AIM: Different types of progenitor cells have been used to improve cardiac conditions after myocardial infarction (MI). Results have shown that while the infusion of a single cell type is safe and feasible, efficacy is modest. Recently, the use of a combination, rather than a single, stem cell product has emerged as an attractive option to improve cardiac outcome after a MI. Before initiating a phase II clinical trial to assess safety and efficacy after the transendocardial infusion of a combination stem cell product, a bench testing assay was designed to validate that delivery through the injection catheter is not associated with cell loss/damage. The latter is important since mesenchymal stem cells (MSC), a component of the cell product, consist of large cells expressing matrix molecules and adhesive receptors. METHODS: The cell product (a mixture of mononuclear cells and MSC) was sequentially injected through a Myostar injection catheter. Exiting fractions were assessed for cell number, viability, capability to restart cell growth and immunophenotype. RESULTS: Cell recovery and viability were high. In turn, exiting cells preserved their biological properties and immunophenotype. CONCLUSIONS: Delivery of cells through a Myostar catheter is safe and not associated with changes in cell survival and/or properties.

Simian varicella virus reactivation in cynomolgus monkeys.

SVV infection of primates closely resembles VZV infection of humans. Like VZV, SVV becomes latent in ganglionic neurons. We used this model to study the effect of immunosuppression on varicella reactivation. Cynomolgus monkeys latently infected with SVV were irradiated and treated with tacrolimus and prednisone. Of four latently infected monkeys that were immunosuppressed and subjected to the stress of transportation and isolation, one developed zoster, and three others developed features of subclinical reactivation. Another non-immunosuppressed latently infected monkey that was subjected to the same stress of travel and isolation showed features of subclinical reactivation. Virus reactivation was confirmed not only by the occurrence of zoster in one monkey, but also by the presence of late SVV RNA in ganglia, and the detection of SVV DNA in non-ganglionic tissue, and SVV antigens in skin, ganglia and lung.

Human T cell leukemia virus type 1 up-regulation after simian immunodeficiency virus-1 coinfection in the nonhuman primate.

The effects that human T cell leukemia virus (HTLV) type 1 and simian immunodeficiency virus (SIV) coinfection have on HTLV-1 dynamics and disease progression were tested in a nonhuman primate model. Seven rhesus macaques were experimentally inoculated with HTLV-1, and a persistent infection was established. Coinfection with SIV/smB670 resulted in increased HTLV-1 p19 antigens in peripheral blood mononuclear cells and HTLV-1 proviral loads. Circulating CD2(+) and CD8(+) T lymphocytes increased over preinoculation levels, along with a progressive decrease in CD4(+) T cells, typical for terminal SIV disease. Finally documented was the striking emergence of up to 19% of HTLV-associated "flower cell" lymphocytes in the circulation, as seen in patients with adult T cell leukemia/lymphoma. CD8(+)CD25(+) T cell subpopulation increases were positively correlated with flower cell appearance and suggested their possible role in this process. We conclude that SIV may have the potential to up-regulate HTLV-1 and disease expression.

Molecular epidemiology of simian T-cell lymphotropic virus type 1 in wild and captive sooty mangabeys.

A study was conducted to evaluate the prevalence and diversity of simian T-cell lymphotropic virus (STLV) isolates within the long-established Tulane National Primate Research Center (TNPRC) colony of sooty mangabeys (SMs; Cercocebus atys). Serological analysis determined that 22 of 39 animals (56%) were positive for STLV type 1 (STLV-1). A second group of thirteen SM bush meat samples from Sierra Leone in Africa was also included and tested only by PCR. Twenty-two of 39 captive animals (56%) and 3 of 13 bush meat samples (23%) were positive for STLV-1, as shown by testing with PCR. Nucleotide sequencing and phylogenetic analysis of viral strains obtained demonstrated that STLV-1 strains from SMs (STLV-1sm strains) from the TNPRC colony and Sierra Leone formed a single cluster together with the previously reported STLV-1sm strain from the Yerkes National Primate Research Center. These data confirm that Africa is the origin for TNPRC STLV-1sm and suggest that Sierra Leone is the origin for the SM colonies in the United States. The TNPRC STLV-1sm strains further divided into two subclusters, suggesting STLV-1sm infection of two original founder SMs at the time of their importation into the United States. STLV-1sm diversity in the TNPRC colony matches the high diversity of SIVsm in the already reported colony. The lack of correlation between the lineage of the simian immunodeficiency virus from SMs (SIVsm) and the STLV-1sm subcluster distribution of the TNPRC strains suggests that intracolony transmissions of both viruses were independent events.