Targeting the aryl hydrocarbon receptor nuclear translocator complex with DMOG and Stemregenin 1 improves primitive hematopoietic stem cell expansion.

Culture conditions used for the expansion of hematopoietic stem and progenitor cells (HSCs and HPCs, collectively HSPCs) should ideally favor the self renewal of long-term HSCs. At 20% O2, the synthesis of HIF-1α is balanced by its hydroxylation and proteasomal degradation. This favors HSPC differentiation, but can be prevented by culturing CD34+ cord blood cells in the presence of dimethyloxaloylglycine (DMOG). This differentiation may also be reduced by culturing the cells in the presence of Stemregenin 1, an antagonist of the aryl hydrocarbon receptor (AhR). The objective of this study was to investigate how hypoxia, DMOG and Stemregenin 1 might affect the expansion of HSPCs with the aim of identifying optimal conditions for expansion in culture. It was found that DMOG decreased proliferation but was effective in preserving the number of cells in the primitive hematopoietic sub-populations in vitro. The effect of DMOG was similar to hypoxia, although differences were observed with regard to the side population and CD34+ sub-populations. Stemregenin 1 on the other hand increased the size of the primitive as well as the other HSC sub-populations. The use of Stemregenin 1 with DMOG increased the proportion of primitive HSCs to 3.54% compared to 2.61% for Stemregenin 1 alone. In vivo engraftment studies confirmed these findings and showed that fewer cells (3710) are required for long-term engraftment when HSCs are grown in Stemregenin 1 together with hypoxia than in Stemregenin 1 under conditions of normoxia (13430).

Opportunities and barriers to establishing a cell therapy programme in South Africa.

The establishment of a cell therapy programme in South Africa has the potential to contribute to the alleviation of the country's high disease burden and also to contribute to economic growth. South Africa has various positive attributes that favour the establishment of such a high-profile venture; however, there are also significant obstacles which need to be overcome. We discuss the positive and negative features of the current health biotechnology sector. The positive factors include a strong market pull and a highly innovative scientific and medical community, while the most problematic features include the lack of human resources and education and limited funding. The South African Government has undertaken to strengthen the biotechnology sector in general, but a focus on cell therapy is lacking. The next important step would be to provide financial, legal/ethical and other support for groups that are active and productive in this field through the development of a local cell therapy programme.