Mouse Neural Stem Cell Differentiation and Human Adipose Mesenchymal Stem Cell Transdifferentiation Into Neuron-and Oligodendrocyte-like Cells With Myelination Potential

Author(s)

Santos, Anderson K. ^[1] ; Gomes, Katia N. ^[1] ; Parreira, Ricardo C. ^{[1, 2, 3]} ; Scalzo, Sergio ^[1] ; Pinto, Mauro C. X. ^[2] ; Santiago, Helton C. ^[1] ; Birbrair, Alexander ^[3] ; Sack, Ulrich ^[4] ; Ulrich, Henning ^{[4, 5]} ; Resende, Rodrigo R. ^[1]

Affiliation

^[1] Univ Fed Minas Gerais, Dept Bioquim & Imunol, Lab Sinalizacao Celular & Nanobiotecnol, Belo Horizonte, MG - Brazil

^[2] Univ Fed Goias, Inst Ciencias Biol, Dept Farmacol, Lab Neuroquim & Neurofarmacol, Goiania, Go - Brazil

^[3] Univ Fed Minas Gerais, Dept Patol, Belo Horizonte, MG - Brazil

^[4] Univ Klinikum Leipzig, Inst Clin Immunol, Leipzig - Germany

^[5] Univ Sao Paulo, Inst Quim, Dept Bioquim, Lab Neurociencias, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: STEM CELL REVIEWS AND REPORTS; NOV 2021.
• Web of Science Citations: 0

Abstract

Stem cell therapy is an interesting approach for neural repair, once it can improve and increase processes, like angiogenesis, neurogenesis, and synaptic plasticity. In this regard, adult neural stem cells (NSC) are studied for their mechanisms of proliferation, differentiation and functionality in neural repair. Here, we describe novel neural differentiation methods. NSC from adult mouse brains and human adipose-derived stem cells (hADSC) were isolated and characterized regarding their neural differentiation potential based on neural marker expression profiles. For both cell types, their capabilities of differentiating into neuron-, astrocyte- and oligodendrocytes-like cells (NLC, ALC and OLC, respectively) were analyzed. Our methodologies were capable of producing NLC, ALC and OLC from adult murine and human transdifferentiated NSC. NSC showed augmented gene expression of NES, TUJ1, GFAP and PDGFRA/Cnp. Following differentiation induction into NLC, OLC or ALC, specific neural phenotypes were obtained expressing MAP2, GalC/O4 or GFAP with compatible morphologies, respectively. Accordingly, immunostaining for nestin(+) in NSC, GFAP(+) in astrocytes and GalC/O4(+) in oligodendrocytes was detected. Co-cultured NLC and OLC showed excitability in 81.3% of cells and 23.5% of neuron/oligodendrocyte marker expression overlap indicating occurrence of in vitro myelination. We show here that hADSC can be transdifferentiated into NSC and distinct neural phenotypes with the occurrence of neuron myelination in vitro, providing novel strategies for CNS regeneration therapy. (AU)

• FAPESP's process: 18/07366-4 - Purine and kinin receptors as targets of study and therapeutic interventions in neurological diseases
• Grantee: Alexander Henning Ulrich
• Support Opportunities: Research Projects - Thematic Grants