Substrate Dependent Galvanotaxis of Directly Reprogrammed Human Neural Precursor Cells

31 Pages Posted: 28 May 2019

See all articles by Umalkhair Ahmed

Umalkhair Ahmed

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Laura Poloni

University of Toronto - Department of Chemical Engineering and Applied Chemistry

Jan-Eric Alfhors

New World Laboratories

Christopher Yip

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Milos Popovic

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Cindi M. Morshead

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Date Written: May 24, 2019

Abstract

Adult neural precursor cells show great promise for the repair of central nervous system (CNS) tissue following injury or disease. Following injury to the CNS, endogenous neural precursor cells (NPCs), found in the neurogenic subventricular zone of the adult forebrain, are activated to proliferate and migrate toward the lesion site. However, this activation is not sufficient for neurorepair. Previous work has demonstrated that murine NPCs are electrosensitive cells that undergo rapid and cathodally directed migration in an applied electric field (EF). Here, we examined the EF induced migration of a clinically relevant human NPC population. With a goal of enhancing cell-based regeneration of the CNS, we explored the role of extracellular matrix (ECM) in human NPC behavior. NPCs plated on matrigel, MaxGel, laminin, and fibronectin were found to migrate in a substrate dependent manner. Common to all substrates was an increase in migration velocity in the presence of an EF. Different, was the direction of migration on the different substrates. The EF application did not induce differentiation on any of the substrates examined, as cells continued to express the precursor markers nestin and SOX2. We determined that secreted factors from neighbouring cells and extracellular pH were not significant factors in EF induced migration, however, substrate stiffness was sufficient to alter the direction of drNPC migration. These findings provide insight into factors that modulate human NPC migration and shed light on considerations for designing cell based therapies for neurorepair.

Keywords: Galvanotaxis, Neural Precursor Cells, Cell Migration, AFM, Cell Migration

Suggested Citation

Ahmed, Umalkhair and Poloni, Laura and Alfhors, Jan-Eric and Yip, Christopher and Popovic, Milos and Morshead, Cindi M., Substrate Dependent Galvanotaxis of Directly Reprogrammed Human Neural Precursor Cells (May 24, 2019). Available at SSRN: https://ssrn.com/abstract=3393754 or http://dx.doi.org/10.2139/ssrn.3393754

Umalkhair Ahmed (Contact Author)

University of Toronto - Institute of Biomaterials and Biomedical Engineering ( email )

Canada

Laura Poloni

University of Toronto - Department of Chemical Engineering and Applied Chemistry

200 College Street
Toronto, Ontario M5S 3E5
Canada

Jan-Eric Alfhors

New World Laboratories

Canada

Christopher Yip

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Canada

Milos Popovic

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Canada

Cindi M. Morshead

University of Toronto - Institute of Biomaterials and Biomedical Engineering

Canada

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