Preclinical research using fresh foetal tissue grafting dates back to four decades ago. Precursor/Progenitor/Stem neural cells were incorporated to the neuro-regeneration research, in the context of ex-vivo gene therapy, by the early 90's.
Later on, the concepts of gene therapy and cell therapy got merged, since the neural stem cells, by themselves, did show their therapeutic potential in the in vivo setting, regardless of any genetic modification
By the late 90's, the successful expansion of human ES was described, a finding that triggered the interest of many research groups in stem cell research, for the development of putative therapies for degenerative disorders.
In the context of developing therapies for human Central Nervous System diseases, little if any progress has been made. The main road-blocks in this research are a) how to limit the proliferation of embryonic stem cells; b) how to extend the proliferative capacity of foetal and adult neural stem cells; c) how to instruct embryonic stem cells to differentiate into the desired neural lineage and not in other cell types; d) how to get stem cell derivatives, of whatever source, differentiating to reach the desired mature functional phenotype once they are grafted, in vivo.
In recent years, investigating how to generate functional human dopaminergic neurons for cell replacement in Parkinson's disease (PD) models, we found that Bcl-XL protein was able to enhance the capacity of forebrain and midbrain human neural stem cells to generate human dopaminergic neurons. We then investigated the actions of Bcl-XL in these hNSCs preparations, finding that: a) Bcl-XL reduces cell death during differentiation by both the usual anti-apoptotic mechanisms, butalso through other yet undefined actions, b) That Bcl-XL induces a biasin the generation of neurons with respect to glial cells, and c) that, at short time points, ventral mesencephalic neural stem cells of human origin induce partial behavioural recovery in parkinsonian rats after transplantation.
Acknowledgements:
La Caixa Foundation, Spanish MEC & MICIN, European Union, NsGene A/S.