The effect of TGF-β1 and BMP-4 on bone marrow-derived stem cell morphology on a novel bioabsorbable nanocomposite material.
BACKGROUND
Congenital heart disease is a leading cause of death in the first year, with an incidence of 1.5 million worldwide. It can be treated with bypass surgery, but due to the limited availability of autologous grafts, there has been research into developing a completely tissue-engineered vascular graft. Our group has developed a small diameter, biodegradable nanocomposite graft which is non-thrombogenic and biostable.


OBJECTIVE
This study looks at the effects of the growth factors, TGF-β1 and BMP-4 on bone marrow-derived stem cell (BMSC) morphology on a POSS PCL scaffold.


METHODS
BMSCs were seeded onto a new nanocomposite of POSS (polyhedral oligomeric silsesquioxane) and PCL (poly[caprolactone-urea]urethane) and TGF-β1 and BMP-4 were used to induce differentiation of the cells to smooth muscle cells. The distribution of the cells was examined using confocal and electron microscopies and the phenotype of the cells was assessed using immunohistochemistry.


RESULTS
It was found that growth factor induction led to a decrease in cell growth on POSS PCL as compared to that of the control surface, and confocal microscopic analysis showed less cytoskeleton reorganization of these cells. After immunohistochemistry analysis, the BMSCs showed no differentiation to smooth muscle cells.


CONCLUSIONS
Growth factor induction on the static scaffold discs led to a change in morphology, with less spreading of the cells, a lower proliferation rate and no differentiation into SMCs. These findings can be attributed to the POSS PCL being manufactured by a coagulation technique, resulting in a structure with low stiffness.
Division of Surgery and Interventional Science, Centre for Nanotechnology and Regenerative Medicine, University College London , London , UK.
Hammad Ahmed
HA
Lakhani
Achala
A
de Mel
Alexander M
AM
Seifalian
D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D055415:Bone Morphogenetic Protein 4 / Q000378:metabolism*; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism; D053761:Nanocomposites / Q000737:chemistry*; D011140:Polyurethanes; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D054457:Tissue Scaffolds / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
C525809:BMP4 protein, human; D055415:Bone Morphogenetic Protein 4; D011140:Polyurethanes; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; C110029:poly(carbonate urea) urethane
bypass graft; congenital heart disease; growth factors; smooth muscle cells; tissue engineering