DOI . ORG {
}
We began analyzing https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.111.300415, but it redirected us to https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.111.300415. The analysis below is for the second page.
Title[redir]:
Smooth Muscle Cells Differentiated From Reprogrammed Embryonic Lung Fibroblasts Through DKK3 Signaling Are Potent for Tissue Engineering of Vascular Grafts | Circulation Research
Description:
Rationale:Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated are limited. Objective:We hypothesized that a large number of SMCs could be obtained by direct reprogramming of fibroblasts, that is, direct differentiation of specific cell lineages before the cells reaching the pluripotent state. Methods and Results:We designed a combined protocol of reprogramming and differentiation of human neonatal lung fibroblasts. Four reprogramming factors (OCT4, SOX2, KLF4, and cMYC) were overexpressed in fibroblasts under reprogramming conditions for 4 days with cells defined as partially-induced pluripotent stem (PiPS) cells. PiPS cells did not form tumors in vivo after subcutaneous transplantation in severe combined immunodeficiency mice and differentiated into SMCs when seeded on collagen IV and maintained in differentiation media. PiPS-SMCs expressed a panel of SMC markers at mRNA and protein levels. Furthermore, the gene dickkopf 3 was found to be involved in the mechanism of PiPS-SMC differentiation. It was revealed that dickkopf 3 transcriptionally regulated SM22 by potentiation of Wnt signaling and interaction with Kremen1. Finally, PiPS-SMCs repopulated decellularized vessel grafts and ultimately gave rise to functional tissue-engineered vessels when combined with previously established PiPS-endothelial cells, leading to increased survival of severe combined immunodeficiency mice after transplantation of the vessel as a vascular graft. Conclusions:We developed a protocol to generate SMCs from PiPS cells through a dickkopf 3 signaling pathway, useful for generating tissue-engineered vessels. These findings provide a new insight into the mechanisms of SMC differentiation with vast therapeutic potential.
Title[redir]:
Smooth Muscle Cells Differentiated From Reprogrammed Embryonic Lung Fibroblasts Through DKK3 Signaling Are Potent for Tissue Engineering of Vascular Grafts | Circulation Research
Description:
Rationale:Smooth muscle cells (SMCs) are a key component of tissue-engineered vessels. However, the sources by which they can be isolated are limited. Objective:We hypothesized that a large number of SMCs could be obtained by direct reprogramming of fibroblasts, that is, direct differentiation of specific cell lineages before the cells reaching the pluripotent state. Methods and Results:We designed a combined protocol of reprogramming and differentiation of human neonatal lung fibroblasts. Four reprogramming factors (OCT4, SOX2, KLF4, and cMYC) were overexpressed in fibroblasts under reprogramming conditions for 4 days with cells defined as partially-induced pluripotent stem (PiPS) cells. PiPS cells did not form tumors in vivo after subcutaneous transplantation in severe combined immunodeficiency mice and differentiated into SMCs when seeded on collagen IV and maintained in differentiation media. PiPS-SMCs expressed a panel of SMC markers at mRNA and protein levels. Furthermore, the gene dickkopf 3 was found to be involved in the mechanism of PiPS-SMC differentiation. It was revealed that dickkopf 3 transcriptionally regulated SM22 by potentiation of Wnt signaling and interaction with Kremen1. Finally, PiPS-SMCs repopulated decellularized vessel grafts and ultimately gave rise to functional tissue-engineered vessels when combined with previously established PiPS-endothelial cells, leading to increased survival of severe combined immunodeficiency mice after transplantation of the vessel as a vascular graft. Conclusions:We developed a protocol to generate SMCs from PiPS cells through a dickkopf 3 signaling pathway, useful for generating tissue-engineered vessels. These findings provide a new insight into the mechanisms of SMC differentiation with vast therapeutic potential.
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Keywords {🔍}
cells, dkk, differentiation, pips, figure, pipssmcs, vessels, cell, crossref, smcs, revealed, pubmed, google, scholar, muscle, reprogramming, human, signaling, vascular, tissueengineered, biology, wnt, centre, markers, oxford, sciences, computational, shanghai, stem, smooth, smc, expression, activation, heart, βcatenin, fibroblasts, vivo, pipssmc, online, ctl, dickkopf, vessel, cardiovascular, promoter, grafts, view, pluripotent, kremen, decellularized, generation,
Topics {✒️}
oct-sox-klf-myc transfection efficiency collagen iv-integrin alpha1/beta1/alphav aha/asa scientific statements partially-induced pluripotent stem vivo animal models american heart association myofiber-derived secreted factor dexamethasone‐induced muscle atrophy fluorescence-activated cell sorting animal models regulate wnt/beta-catenin signalling tissue-engineered vascular grafts tissue-engineered vascular grafts tissue-engineered grafts leads submit carotid artery generating tissue-engineered vessels pips cell-derived vessels pips cell–derived vessels pips-smc-dkk3 cells leads online figures xiii online figures xv red ™ aha induced pluripotent stem make patient-specific therapy functional tissue-engineered vessels smooth muscle cells hydrogel-based culture methods supplements download pdf pips tissue-engineered vessels smooth muscle actin main content advertisement heart failure stroke circulation research tissue-engineered vessels revealed pips-smc-dkk3-stimulated cells smooth muscle differentiation pips-smc-dkk3 cells revealed β-catenin destruction complex engineered vascular grafts wnt-beta-catenin pathway british heart foundation serum-free media vascular tissue engineering european polymer journal intermediate pluripotent state β-catenin nuclear translocation coronary artery disease drive pips-smc differentiation dickkopf-3-related gene regulates
Questions {❓}
- Juan Du,Xuelai Liu,Carol Wing Yan Wong,Kenneth Kak Yuen Wong,Zhixin Yuan,Direct cellular reprogramming and transdifferentiation of fibroblasts on wound healing—Fantasy or reality?
- What Is Known?
- What New Information Does This Article Contribute?
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