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Nonviral Reprogramming Genes Accelerate Formation of Neurons from Murine Embryonic Brain Cells: Synergistic Effect of Brain Derived Neurotrophic Factor Gene Therapy

Liu G*

Introduction: The lesser quantity products of reprogrammed stem cells and slower differentiation of stem cells into neurons have limited the advance of cell therapy in clinical applications. Neurotrophic factors BDNF, GDNF, FGF, and IGF are critical factors for further differentiation and proliferation of neuronal cells. However, the influence of the reprogramming genes on the neurotrophic factors is unclear.

Methods: Murine primary embryonic brain cells were transfected with cDNA constructs combining non-viral reprogramming genes and with/without complete length cDNA constructs of these neurotrophic factors. Reprogrammed iPSCs and progressive differentiated neural cells and controls were observed using methods of imaging and quantities.

Results: Our results suggested: 1) During time-courses from the transformation of iPSCs into progressively staged neuron cells, the non-viral reprogramming genes have been significantly accelerated formations of progenitor cells, neuron cells, and neuron network, respectively. 2) The non-viral reprogramming genes directly increased gene expressions of BDNF, GDNF, FGF and IGF at RNA levels. 3) cDNA BDNF plus reprogramming genes showed a robust induction of the immature neuronal marker doublecortin at the protein level.

Conclusion: This study presents a high-efficiency approach for producing non-viral reprogrammed stem cells and auxiliary differentiated neuronal cells, which would potentially apply in the future clinical applications.