Mechanical induction of dentin-like differentiation by adult mouse bone marrow stromal cells using compressive scaffolds.

Tooth formation during embryogenesis is controlled through a complex interplay between mechanical and chemical cues. We have previously shown that physical cell compaction of dental mesenchyme cells during mesenchymal condensation is responsible for triggering odontogenic differentiation during embryogenesis, and that expression of Collagen VI stabilizes this induction. In addition, we have shown that synthetic polymer scaffolds that artificially induce cell compaction can induce embryonic mandible mesenchymal cells to initiate tooth differentiation both in vitro and in vivo.

Mesenchymal condensation-dependent accumulation of collagen VI stabilizes organ-specific cell fates during embryonic tooth formation.

Background: Mechanical compression of cells during mesenchymal condensation triggers cells to undergo odontogenic differentiation during tooth organ formation in the embryo. However, the mechanism by which cell compaction is stabilized over time to ensure correct organ-specific cell fate switching remains unknown.

Results: Here, we show that mesenchymal cell compaction induces accumulation of collagen VI in the extracellular matrix (ECM), which physically stabilizes compressed mesenchymal cell shapes and ensures efficient organ-specific cell fate switching during tooth organ development.

Developmentally-inspired shrink-wrap polymers for mechanical induction of tissue differentiation.

A biologically inspired thermoresponsive polymer has been developed that mechanically induces tooth differentiation in vitro and in vivo by promoting mesenchymal cell compaction as seen in each pore of the scaffold. This normally occurs during the physiological mesenchymal condensation response that triggers tooth formation in the embryo.

A combinatorial cell-laden gel microarray for inducing osteogenic differentiation of human mesenchymal stem cells.

Development of three dimensional (3D) microenvironments that direct stem cell differentiation into functional cell types remains a major challenge in the field of regenerative medicine. Here, we describe a new platform to address this challenge by utilizing a robotic microarray spotter for testing stem cell fates inside various miniaturized cell-laden gels in a systematic manner. To demonstrate the feasibility of our platform, we evaluated the osteogenic differentiation of human mesenchymal stem cells (hMSCs) within combinatorial 3D niches.

Circulating CD34(+) progenitor cell frequency is associated with clinical and genetic factors.

Circulating blood CD34(+) cells consist of hematopoietic stem/progenitor cells, angiogenic cells, and endothelial cells. In addition to their clinical use in hematopoietic stem cell transplantation, CD34(+) cells may also promote therapeutic neovascularization. Therefore, understanding the factors that influence circulating CD34(+) cell frequency has wide implications for vascular biology in addition to stem cell transplantation.

Genetic and clinical correlates of early-outgrowth colony-forming units.

Background: Several bone marrow-derived cell populations may have angiogenic activity, including cells termed endothelial progenitor cells. Decreased numbers of circulating angiogenic cell populations have been associated with increased cardiovascular risk. However, few data exist from large, unselected samples, and the genetic determinants of these traits are unclear.

Association of colony-forming units with coronary artery and abdominal aortic calcification.

Background: Certain bone marrow-derived cell populations, called endothelial progenitor cells, have been reported to possess angiogenic activity. Experimental data suggest that depletion of these angiogenic cell populations may promote atherogenesis, but limited data are available on their relation to subclinical atherosclerotic cardiovascular disease in humans.

Methods And Results: We studied 889 participants of the Framingham Heart Study who were free of clinically apparent cardiovascular disease (mean age, 65 years; 55% women).