Over-expression of Oct4 and Sox2 transcription factors enhances differentiation of human umbilical cord blood cells in vivo

•Gene and cell-based therapies comprise innovative aspects of regenerative medicine.•Genetically modified hUCB-MCs enhanced differentiation of cells in a mouse model of ALS.•Stem cells successfully transformed into micro-glial and endothelial lines in spinal cords.•Over-expressing oct4 and sox2 also induced production of neural marker PGP9.5.•Formation of new nerve cells, secreting trophic factors and neo-vascularisation could improve symptoms in ALS. Gene and cell-based therapies comprise innovative aspects of regenerative medicine. Even though stem cells represent a highly potential therapeutic strategy, their wide-spread exploitation is marred by ethical concerns, potential for malignant transformation and a plethora of other technical issues, largely restricting their use to experimental studies. Utilizing genetically modified human umbilical cord blood mono-nuclear cells (hUCB-MCs), this communication reports enhanced differentiation of transplants in a mouse model of amyotrophic lateral sclerosis (ALS). Over-expressing Oct4 and Sox2 induced production of neural marker PGP9.5, as well as transformation of hUCB-MCs into micro-glial and endothelial lines in ALS spinal cords. In addition to producing new nerve cells, providing degenerated areas with trophic factors and neo-vascularisation might prevent and even reverse progressive loss of moto-neurons and skeletal muscle paralysis.