Gene expression from lamina propria of olfactory mucosa from Human. Homo sapiens

The establishment of induced pluripotent stem (iPS) cells methodologies has widened the possibilities of stem cell related clinical therapies. However, safety concerns over current reprogramming technologies as well as lack of efficient protocols for differentiation raise serious questions over their usage in clinical settings. Direct lineage conversion may represent a safer technology for cell-therapy. Here, we identify Sox2 as a factor able to transdetermine human mesenchymal stem cells (MSCs) to hematopoietic progenitor cells (HPCs), recapitulating the molecular events during in vivo hematopoiesis. This technology offers an efficiency of up to 70% HPC generation in less than 8 days under feeder-free conditions. With the goal of devising ways for transplantation into diseased patients we developed two different methodologies that avoid exogenous DNA integration or viral infections. The first, by transduction of recombinant Sox2 protein, and the second by functional replacement of Sox2 by inhibition of TGFß signaling. The DNA integration-, virus-, and feeder-free transdetermination system here described may complement and enhance current approaches for autologous as well as heterologous HPC transplantation in humans. Overall design: Mesenchymal Stem Cells were transdifferentiated towards the hematopoietic lineage.