Effects of powder type, particle size (5-20 microm; 90-300 microm; 90-710 microm), and type of dissolution medium on the dissolution behavior of bioactive glasses were investigated in vitro using melt-derived 45S5 and sol-gel derived 58S bioactive glass powders. Dissolution studies were performed in simulated body fluid and in alpha-MEM based cell culture medium at 37 degrees C under dynamic conditions (1 Hz) for periods of 30 min, 1, 2, 4, 8, 17, and 22 h. The concentrations of elements dissolved from the glasses were evaluated using inductively coupled plasma analysis. The reacted powders were analyzed for bioactivity using Fourier transform infrared spectrometry to observe the formation of a calcium phosphate layer on the surface. The non-porous surfaces of melt-derived 45S5 glass powders exhibited lower dissolution rates and rate of surface layer formation than 58S gel-glass powders. The rates of dissolution for both types of powders were lower in culture medium, compared to simulated body fluid, and increased as the particle size decreased. Thus, particle size range, glass type, and powder volume fraction can be used as a means to control the release rate of active ions that stimulate the gene expression and cellular response for tissue proliferation and repair.

Bioactive glasses are known to have the ability to regenerate bone, but their use has been restricted mainly to powder, granules, or small monoliths. This work reports on the development of sol-gel foams with potential applications as bone graft implants or as templates for the in vitro synthesis of bone tissue for transplantation. These bioactive foams exhibit a hierarchical structure with interconnected macropores (10-500 microm) and a mesoporous framework typical of gel-glasses (pores of 2-50 nm). The macroporous matrixes were produced through a novel route that comprises foaming of sol-gel systems. Three glass systems were tested to verify the applicability of this manufacturing route, namely SiO(2), SiO(2)-CaO, and SiO(2)-CaO-P(2)O(5). This new class of material combines large pores to support vascularization and 3-D tissue growth with the ability that bioactive materials have to provide bone-bonding and controlled release of ionic biologic stimuli to promote bone cell proliferation by gene activation.

Human dental pulp contains precursor cells termed dental pulp stem cells (DPSC) that show self-renewal and multilineage differentiation and also secrete multiple proangiogenic and antiapoptotic factors. To examine whether these cells could have therapeutic potential in the repair of myocardial infarction (MI), DPSC were infected with a retrovirus encoding the green fluorescent protein (GFP) and expanded ex vivo. Seven days after induction of myocardial infarction by coronary artery ligation, 1.5 ؋ 10 6 GFP-DPSC were injected intramyocardially in nude rats. At 4 weeks, cell-treated animals showed an improvement in cardiac function, observed by percentage changes in anterior wall thickening left ventricular fractional area change, in parallel with a reduction in infarct size. No histologic evidence was seen of GFP ؉ endothelial cells, smooth muscle cells, or cardiac muscle cells within the infarct. However, angiogenesis was increased relative to control-treated animals. Taken together, these data suggest that DPSC could provide a novel alternative cell population for cardiac repair, at least in the setting of acute MI. STEM CELLS 2008;26:638 -645 Disclosure of potential conflicts of interest is found at the end of this article.

Insufficient vessel growth associated with ischemia remains an unresolved issue in vascular medicine. Mesenchymal stem cells (MSCs) have been shown to promote angiogenesis via a mechanism that is potentiated by hypoxia. Overexpression of hypoxia inducible factor (HIF)-1α in MSCs improves their therapeutic potential by inducing angiogenesis in transplanted tissues. Here, we studied the contribution of exosomes released by HIF-1α-overexpressing donor MSCs (HIF-MSC) to angiogenesis by endothelial cells. Exosome secretion was enhanced in HIF-MSC. Omics analysis of miRNAs and proteins incorporated into exosomes pointed to the Notch pathway as a candidate mediator of exosome communication. Interestingly, we found that Jagged1 was the sole Notch ligand packaged into MSC exosomes and was more abundant in HIF-MSC than in MSC controls. The addition of Jagged1-containing exosomes from MSC and HIF-MSC cultures to endothelial cells triggered transcriptional changes in Notch target genes and induced angiogenesis in an in vitro model of capillary-like tube formation, and both processes were stimulated by HIF-1α. Finally, subcutaneous injection of Jagged 1-containing exosomes from MSC and HIF-MSC cultures in the Matrigel plug assay induced angiogenesis in vivo, which was more robust when they were derived from HIF-MSC cultures. All Jagged1-mediated effects could be blocked by prior incubation of exosomes with an anti-Jagged 1 antibody. All together, the results indicate that exosomes derived from MSCs stably overexpressing HIF-1α have an increased angiogenic capacity in part via an increase in the packaging of Jagged1, which could have potential applications for the treatment of ischemia-related disease. Stem Cells 2017;35:1747-1759.