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

Gemma E. Rooney, Cathal Moran, Siobhan S. McMahon, Thomas Ritter, Martin Maenz, Alexander Flügel, Peter Dockery, Timothy O'Brien, Linda Howard, Anthony J. Windebank, Frank P. Barry

Research output: Contribution to journalArticle

43 Scopus citations

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 (∼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 that MSCs are a good candidate for delivery of therapeutic factors into the injured nervous system. They are autologous, may be genetically modified to express neurotrophins, and are compatible with polymer surfaces that may be used as a potential delivery system.

Original languageEnglish (US)
Pages (from-to)681-690
Number of pages10
JournalTissue Engineering - Part A.
Volume14
Issue number5
DOIs
StatePublished - May 1 2008

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

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    Rooney, G. E., Moran, C., McMahon, S. S., Ritter, T., Maenz, M., Flügel, A., Dockery, P., O'Brien, T., Howard, L., Windebank, A. J., & Barry, F. P. (2008). Gene-modified mesenchymal stem cells express functionally active nerve growth factor on an engineered poly lactic glycolic acid (PLGA) substrate. Tissue Engineering - Part A., 14(5), 681-690. https://doi.org/10.1089/tea.2007.0260