Title
Non-virally modified human mesenchymal stem cells produce ciliary neurotrophic factor in biodegradable fibrin-based 3D scaffolds
Author
Antos Shakhbazau, Dzmitry Shcharbin, Natalya Petyovka, Natalya Goncharova, Ihar Seviaryn, Svetlana Kosmacheva, Maria Bryszewska, Mihail Potapnev
Year
2011
Journal
Journal of Pharmaceutical Sciences
Abstract
We report the adaptation of dendrimer-based nonviral expression system for ciliary neurotrophic factor (CNTF) overproduction in human mesenchymal stem cells (hMSCs) embedded into fibrin-based three-dimensional (3D) matrix. Time-restricted neurotrophin expression enables autologous adult stem cells for additional trophic support and increases their therapeutic potential in neuroregeneration applications. Polyamidoamine (PAMAM)–NH2 dendrimers of fourth generation effectively provided virus-free delivery and expression of CNTF–internal ribosome entry site–green fluorescent protein cassette with a transfection efficiency in hMSCs over 11%. CNTF levels in transfected cultures were 10-fold higher as compared with the control cells. Dendrimer-driven CNTF expression also persisted in hMSCs embedded into fibrin-based 3D matrix, an emerging vehicle for cell delivery or bioartificial organ formation. Nonviral modification of autologous adult stem cells with use of dendrimers is a novel tool perspective in terms of biosafety and technological availability.
Instrument
FP-6300
Keywords
Fluorescence, DNA structure, Ligand binding, Pharmaceutical, Biochemistry