Non-virally modified human mesenchymal stem cells produce ciliary neurotrophic factor in biodegradable fibrin-based 3D scaffolds.
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)-NH(2) 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.
Department of Clinical Neuroscience, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada.
Antos
A
Shakhbazau
Dzmitry
D
Shcharbin
Natalya
N
Petyovka
Natalya
N
Goncharova
Ihar
I
Seviaryn
Svetlana
S
Kosmacheva
Maria
M
Bryszewska
Mihail
M
Potapnev
D001673:Biodegradation, Environmental; D002478:Cells, Cultured; D020934:Ciliary Neurotrophic Factor / Q000096:biosynthesis*; D050091:Dendrimers / Q000737:chemistry; D005337:Fibrin / Q000008:administration & dosage*; D015316:Genetic Therapy; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D014162:Transfection
D020934:Ciliary Neurotrophic Factor; D050091:Dendrimers; C104700:PAMAM Starburst; D005337:Fibrin