Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System | Zendy

Christian H. Bucher | Zendy; Amiq Gazdhar | Zendy; Lorin M. Benneker | Zendy; Thomas Geiser | Zendy; Benjamin Gantenbein | Zendy

Open Access

Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

Author(s) -

Christian H. Bucher,

Amiq Gazdhar,

Lorin M. Benneker,

Thomas Geiser,

Benjamin Gantenbein

Publication year - 2013

Publication title -

stem cells international

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.205

H-Index - 64

eISSN - 1687-9678

pISSN - 1687-966X

DOI - 10.1155/2013/326828

Subject(s) - mesenchymal stem cell , aggrecan , electroporation , transfection , chondrogenesis , microbiology and biotechnology , transplantation , regenerative medicine , gene delivery , tissue engineering , stem cell , cell culture , chemistry , biology , biomedical engineering , pathology , medicine , gene , articular cartilage , surgery , osteoarthritis , biochemistry , genetics , alternative medicine

Intervertebral disc (IVD) cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC) is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5) by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

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