SAMRC Extramural Stem Cell Unit

According to the World Economic Forum’s 2013-2014 Global Competitiveness Index (GCI), South Africa is ranked only 53rd out of 148 countries, one of the major reasons being the  high burden of disease which includes communicable (infectious) and non-communicable (including diseases of lifestyle and cancer). The MRC Extramural Research Unit for ‘Stem Cell Research and Therapy’ will provide a multidisciplinary approach aimed at contributing to the alleviation of communicable and non-communicable diseases in South Africa.

Our main focus is on adult stem cells, namely hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). Our first objective is to use HSCs to generate an HIV-resistant immune system. Although our initial objective has been to use a lentiviral-based approach to knock down CCR5, one of the two HIV co-receptors, we are identifying other potential host targets. We have established a colony of immunodeficient mice at the UP Biomedical Research Center at Onderstepoort, and will use these mice to generate “humanized mice” i.e. mice which have a human immune system, and which therefore can be infected with HIV, to study not only the efficacy of our gene therapy approaches, but also settings such as HIV and TB co-infection. We hope to use this project to initiate a gene therapy platform, from which gene therapy projects for other diseases will follow.

The HIV gene therapy project has several facets, including the identification of primitive HSC populations, determination of the infectability of primitive HSCs by HIV; expansion techniques for HSCs; possible use of G-CSF-mobilized peripheral blood HSCs in addition to cord blood HSCs for gene therapy purposes; improvement in transduction efficiency;pre-and post-transplantation selection techniques; and the study of HLA diversity in southern African populations.

With regard to MSCs, our goal is to establish a clean room facility in order to provide cell therapy products for MSC clinical trials. A great deal still remains to be understood about MSC heterogeneity, differentiation capacity in vivo, homing properties, and optimal growth conditions in vitro including the elimination of xenogeneic products. With regard to heterogeneity, we are well placed to analyze MSC subpopulations through the use of our recently acquired FacsAria Fusion Cell Sorter, and with the aid of the Fluidigm microfluidics platform we will be able to study single cell transcriptomics and thereby understand the molecular basis of this heterogeneity. With regard to differentiation, our focus is on adipogenesis. To this end we have established multiparameter assays of adipogenesis which allow us to identify cells at various stages of differentiation.

In addition to our work on adult stem cells, we have initiated a programme on somatic cell nuclear transfer in collaboration with Prof Carin Huyser and her colleagues at the Reproductive Biology Laboratory at Steve Biko Academic Hospital.

A major component of our work will continue to address the ethical, legal and social implications/consequences of the work we are doing on stem cells.

Visit our page on the South African Medical Research Council (SAMRC) website

Published by Ansa Heyl

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