Abstract
BackgroundInduced pluripotent stem cells (iPSC) are generated by reprogramming somatic cells into embryonic like state (ESC) using defined factors. There is great interest in these cells because of their potential for application in regenerative medicine.ResultsiPSC reprogrammed from murine tail tip fibroblasts were exposed to retinoic acid alone (RA) or in combination with TGF-β1 and 3, basic fibroblast growth factor (bFGF) or bone morphogenetic protein 2 (BMP-2). The resulting cells expressed selected putative mesenchymal stem cells (MSCs) markers; differentiated toward osteoblasts and adipocytic cell lineages in vitro at varying degrees. TGF-beta1 and 3 derived-cells possessed higher potential to give rise to osteoblasts than bFGF or BMP-2 derived-cells while BMP-2 derived cells exhibited a higher potential to differentiate toward adipocytic lineage. TGF-β1 in combination with RA derived-cells seeded onto HA/TCP ceramics and implanted in mice deposited typical bone. Immunofluorescence staining for bone specific proteins in cell seeded scaffolds tissue sections confirmed differentiation of the cells into osteoblasts in vivo.ConclusionsThe results demonstrate that TGF-beta family of proteins could potentially be used to generate murine iPSC derived-cells with potential for osteoblasts differentiation and bone formation in vivo and thus for application in musculoskeletal tissue repair and regeneration.
Highlights
Induced pluripotent stem cells are generated by reprogramming somatic cells into embryonic like state (ESC) using defined factors
Cells derived by retinoic acid alone (RA) alone treatment contained cells with a spindle morphology but there were more cells with rounded morphology when compared to TGF-beta 1 or 3 population
The results showed that TGF-β1 and 3 in combination with RA were more effective in generating cells from Induced pluripotent stem cells (iPSC) with ability to give rise to osteoblasts and make bone in ceramics implanted in mice
Summary
Induced pluripotent stem cells (iPSC) are generated by reprogramming somatic cells into embryonic like state (ESC) using defined factors. More work is still needed to get iPSC closer to clinical application, it is critical to begin to understand factors that play a role in directing differentiation of iPSC to various cell lineages prior to clinical application. In this regard, several studies focusing on methods to direct iPSC to specific cell lineages are active areas of investigation [16,17,18,19]. This proof of concept demonstrated that it was possible to direct iPSC to hematopoietic lineage efficiently at least for murine iPSC
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