Regenerative mechanisms induced by application of progenitor cells in spinal cord and liver injuries

AQUINO JB

Chiclayo

Jornada; VI Jornada Internacional de Genética ?66 years of 46 Human Chromosomes? Últimos Avances en Genética y Biología Molecular; 2022

The International Circle of Genetic Studies

We have explored the regenerative role of different adult tissue-specific progenitors. Boundary cap neural crest stem cells (BCNCSCs) were isolated from mouse embryos and differentiated in vitro into Schwann cells. The application of these BCNCSCs-derived Schwann cells at the site of injury in the rat spinal cord (weight drop model) resulted in a significant improvement in BBB locomotor test, relative to the control group. This was associated with an induction of endogenous spinal cord progenitors which served as scaffold for corticomotor axonal regeneration and with a reduction in the incidence of reactive macrophages. In another project, using a mouse genetic lineage tracing model, it has been described that mature Schwann cells of the myelinating lineage are capable of dedifferentiating in vivo until they reach characteristics of glial/melanocytic progenitors. Finally, the application of mesenchymal stromal cells (MSCs) as vehicles for gene therapy with IGF-I resulted in the amelioration of liver fibrosis in mouse, in part through the induction of hepatocyte proliferation. A peak in hepatic expression of the trophic factors IGF-I and HGF is observed at 1 day after MSCs application, and 2 days later a reduction in the levels of profibrogenic factors was observed. The exogenous overexpression of IGF-I resulted in a greater induction of these mechanisms. The application of multiple doses of MSCs genetically modified to express IGF-I resulted in an even greater reduction in the degree of hepatic collagen accumulation. These liver regenerative mechanisms were dependent on macrophages.