1. Guiding the osteogenic fate of mouse and human mesenchymal stem cells through feedback system control.
- Author
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Honda Y, Ding X, Mussano F, Wiberg A, Ho CM, and Nishimura I
- Subjects
- Animals, Bone Morphogenetic Proteins metabolism, Culture Media chemistry, Culture Media pharmacology, Humans, Mesenchymal Stem Cells drug effects, Mice, Signal Transduction drug effects, Smad Proteins metabolism, Cell Differentiation drug effects, Mesenchymal Stem Cells cytology, Mesenchymal Stem Cells metabolism, Models, Biological, Osteogenesis drug effects
- Abstract
Stem cell-based disease modeling presents unique opportunities for mechanistic elucidation and therapeutic targeting. The stable induction of fate-specific differentiation is an essential prerequisite for stem cell-based strategy. Bone morphogenetic protein 2 (BMP-2) initiates receptor-regulated Smad phosphorylation, leading to the osteogenic differentiation of mesenchymal stromal/stem cells (MSC) in vitro; however, it requires supra-physiological concentrations, presenting a bottleneck problem for large-scale drug screening. Here, we report the use of a double-objective feedback system control (FSC) with a differential evolution (DE) algorithm to identify osteogenic cocktails of extrinsic factors. Cocktails containing significantly reduced doses of BMP-2 in combination with physiologically relevant doses of dexamethasone, ascorbic acid, beta-glycerophosphate, heparin, retinoic acid and vitamin D achieved accelerated in vitro mineralization of mouse and human MSC. These results provide insight into constructive approaches of FSC to determine the applicable functional and physiological environment for MSC in disease modeling, drug screening and tissue engineering.
- Published
- 2013
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