Matrigel supports survival and neuronal differentiation of grafted embryonic stem cell‐derived neural precursor cells

Abstract

Cell replacement therapy holds great promise as a means of treating neurological disorders, including Parkinson's disease. However, one of the major obstacles to the success of this treatment is the low survival rate of grafted cells, which probably results from mechanical damage, acute inflammation, and immunological rejection. To overcome this problem, we investigated the effect of different types of extracellular matrix (ECM) on the survival and differentiation of embryonic stem (ES) cell-derived neural precursor cells (NPCs). We tested materials from natural sources, including collagen, ornithine/laminin, and growth factor-reduced Matrigel (gfrMG), as well as the synthetic biomaterial PuraMatrix, which consists of self-assembling polypeptides. GfrMG efficiently supported cell survival, migration, and neurite outgrowth in vitro and promoted proliferation of grafted cells in vivo, resulting in larger graft volume and an increase in the number of TH-positive dopaminergic neurons in the graft. GfrMG did not induce dopaminergic differentiation directly; rather, it reduced the invasion of pan-leukocytic CD45-positive cells into the graft. Insofar as the inflammatory or immune response in the host brain inhibits neuronal differentiation of grafted NPCs, gfrMG may increase the number of TH-positive cells by suppressing this effect. Thus, gfrMG appears to provide a suitable scaffold that supports survival and differentiation of NPCs. However, because it is derived from mouse sarcomas, a human-derived matrix or synthetic biomaterial must be developed for clinical applications.

Nerve growth factor induces cord formation of mesenchymal stem cell by promoting proliferation and activating the PI3K/Akt signaling pathway

“…The Matrigel assay is commonly considered to be an experimental method that measures the ability of cells to promote angiogenesis in vitro [15] and is also used to support the differentiation of neural precursor cells into neuronal cells [16] . NGF is a common neurotrophic factor, so we needed to exclude the possibility that MSCs normally have the ability to differentiate into neuronal cells.…”

“…This result indicated that tubes formed in Matrigel may differentiate into endothelial cells. Because the Matrigel can also support neuronal differentiation of neural precursor cells [16] , we examined whether the MSCs differentiated into neurocytes. MSCs were positively expressing early neuronal markers and some mature neuronal markers.…”

Harnessing the Potential of Biomaterials for Brain Repair after Stroke

“…One natural hydrogel used for cell delivery is Matrigel™, a material derived from a mouse sarcoma cell line primarily composed of laminin-1 and collagen IV and containing many adhesive molecules and growth factors that promote cell viability. Transplantation of mouse ESC-derived NPCs in Matrigel™ into the striatum resulted in a larger graft volume and increased the number of tyrosine hydroxylase-positive dopaminergic neurons (Uemura et al, 2010). Unfortunately, as Matrigel™ is derived from a xenobiotic source, it has high batch-to-batch variability and is unsuitable for clinical use (Jin et al, 2010).…”

MatrigelBD, A Biocompatible Scaffold that Improves Gingival Mesenchymal Stem Cells Proliferation

“…MatrigelBD is a solubilized basement membrane extracted from Engelbreth-HolmSwarm (EHS) mouse sarcoma (Hughes et al, 2010). In preliminary studies, MatrigelBD has been used in cardiomyocyte progenitor transplantation experiments, in a cardiac infarction animal model, and to promote in vivo angiogenesis (Ou et al, 2011;Bhat et al, 2012), and stimulates embryonic stem cells (ESC) to survive and differentiate in vitro (Uemura et al, 2010). One report showed that dental pulp stem cells (DPSC) co-cultured within MatrigelBD maintained their osteogenic differentiation potential, suggesting possible applications for use in skeletal defects (van Gastel et al, 2012).…”