Poly , cell transplant studies

Nicotinamide and benzamide are inhibitors of the chromatin bound enzyme poly(ADP-ribose) polymerase (3, 8), and inhibitors of poly(ADP-ribose) polymerase are known radiosensitizers (1,4). In a previous study (6) we have shown that low doses of nicotinamide given oraUy to mice from day of transplantation until day of radiation sensitizes a C3H mammary adenocarcinoma to radiation. Nicotinamide not only is an inhibitor of poly(ADP-ribose) polymerase but also has metabolic effects on the cell. Thus it is known that nicotinamide can increase the NAD pool in both malignant and normal cells (2, 7). Horsman et al. (4) have also indicated metabolic effects on the circulation with nicotinamide. Our results with per os administered benzamide indicate a difference in the radiosensitizing action of nicotinamide and benzamide. Nicotinamide can have radiosensitizing properties other than a simple direct poly(ADP-ribose)... 

The Lavik lab has further expanded the work with these scaffolds to assess the effect of transplanting NSCs in combination with endothelial cells, to explore the effects of vascularization on recovery after SCI (Rauch et al. 2009). They found that transplantation of both cell types within a polyethylene glycol/ poly-L-lysine hydrogel inside the PLGA scaffolds increased functional blood vessel formation over controls however, there were fewer NSCs in the cotransplant groups compared to those with NSCs alone. No functional recovery was observed in this study however, this may be an interesting approach to evaluate recapitulation of a neurovascular stem cell niche. 

Synthetic porous scaffolds, or matrices, have also been used for injecting stem cells. PG matrices have been seeded with mouse ES cells and injected into a mouse infarct. After 8 weeks, cells were viable within the matrix and improved cardiac function and vascularization however, there was no evidence that transplanted cells differentiated directly into vascular or myocardial cells (Ke et al., 2005). In a similar study, poly(lactide-co-caprolactone) was used to deliver MSC into the infarct, where the addition of the polymer improved cell survival and cardiac function (Jin et al., 2009). These studies suggest that similar to natural polymers, both adult and ES cells can be dehvered with synthetic polymers with positive in vivo outcomes. However, more than just a dehvery vehicle, synthetic materials offer the ability to introduce biological cues. 

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