Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid (PLGA) substrate

Tissue Engineering. Part a
Gemma E RooneyFrank P Barry

Abstract

Delivery of cellular and/or trophic factors to the site of injury may promote neural repair or regeneration and return of function after peripheral nerve or spinal cord injury. Engineered scaffolds provide a platform to deliver therapeutic cells and neurotrophic molecules. We have genetically engineered mesenchymal stem cells (MSCs) from the green rat (CZ-004 [SD TgN(act-EGFP)OsbCZ-004]) to express nerve growth factor (NGF) using an adenoviral vector. Cells maintained their stem cell phenotype as judged by expression of CD71 and CD172 markers, and absence of the hematopoietic marker CD45. Cells continued to express green fluorescent protein (GFP) on a long-term basis. Morphology, viability, and growth kinetics were maintained when cells were grown on a poly-lactic-co-glycolic acid (PLGA) polymer scaffold. Under appropriate growth conditions, they differentiated into chondrogenic, osteogenic, and adipogenic phenotypes, demonstrating that they retained their characteristics as MSCs. NGF was secreted from transduced MSCs at physiologically relevant levels ( approximately 25 ng/mL) measured by enzyme-linked immunoabsorbent assay (ELISA). Secreted NGF was functionally active in a neurite growth assay with PC12 cells. We conclude tha...Continue Reading

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Citations

Apr 1, 2009·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Kerry Thompson
Feb 26, 2011·Journal of Tissue Engineering·Jung Keun Hyun, Hae-Won Kim
Aug 1, 2009·Stem Cell Reviews and Reports·Peter A WalkerCharles S Cox
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Mar 12, 2015·Tissue Engineering. Part a·Adam J MellottMichael S Detamore
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Sep 27, 2018·Gene Therapy·Wei WeiWei Wang
Dec 13, 2017·Macromolecular Bioscience·Zhen-Hua WangWei-Fang Su
Nov 10, 2020·Tissue Engineering. Part a·Meer N AhmedFatima N Syed-Picard
Aug 11, 2021·Experimental and Therapeutic Medicine·Ying LiJianliang Pang
Jul 13, 2015·ACS Biomaterials Science & Engineering·Teresa C MoloneyEilís Dowd

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