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Neuronal commitment of Umbilical Cord Mesenchymal Stem Cells for brain regenerative medicine


Nowadays, no effective prevention or cure of human brain diseases is available. Stem cells hold great promise for the repair and regeneration of damaged neural tissues. This thesis aims to evaluate the potency of human umbilical cord mesenchymal stem cells (hUC MSCs) to be committed to the neuronal lineage, for brain cell-based therapy. To achieve this goal, naive hUC MSCs were isolated, expanded, and characterized at the gene and protein level, while particularly focusing on the neuronal lineage and clinical-grade culture conditions. Then, several parameters were investigated for hUC MSCs proliferation and neuronal commitment, including media, coatings, 3D culture, hypoxia, chemicals and molecules. Growth curves drawings, qPCRs, and immunostainings were used among other methods for identifying the best conditions for hUC MSCs expansion, differentiation, culture in 3D, and microRNAs delivery. The results indicate that hUC MSCs better proliferate in serum-free media and brain's normoxia condition (1-5 % O2). Naive hUC MSCs appear primed for neuronal fate at gene and protein level, but not su_ciently to support their neuronal di_erentiation. microRNAs delivery requires further improvement to efficiently promote neuronal signaling pathways in hUC MSCs. Along this study we identified the best parameters for hUC MSCs expansion in clinical-grade conditions. However, a question still remains: are hUC MSCs capable of full transdifferentiation towards functional neurons despite all controversies? Additional work is needed, but this study is a first step towards answering this question, bringing more clues to make transplantation of hUC MSCs for brain regenerative medicine closer

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