Earlier in 2009, Cai et al. studied the role of LIM homeobox transcription factor 1a (Lmx1a) in the differentiation of human ESCs into mDA precursor cells in vitro and after transplantation into a PD model (Cai et al., 2009). Lmx1a is known to autoregulate and control mDA neurons synergistically with the SHH-FoxA2 pathway (Chung et al., 2009). Results have shown that only Lmx1a-expressing human neuronal progenitor cells have the potential to differentiate into mDA neurons after transplantation into the 6-OHDA rat striatum (Cai et al., 2009). This is of great importance for the development of suitable re-placement tissue for the functional recovery from PD (Cai et al., 2009). Consequently, a complete potential of iPSCs to differentiate into DA neurons is revealed once EB cells, derived from iPSCs transfected by a lentivirus, were forced to express the ventral midbrain determinant Lmx1a, together with DA neuron patterning factor. This resulted in the differentiation of EBs into functional mDA, the cell type mostly affected in PD (Sánchez-Danés et al., 2012).
