scholarly journals Bone Marrow Mesenchymal Stem Cells Stabilize Already-formed Aortic Aneurysms More Efficiently than Vascular Smooth Muscle Cells in a Rat Model

2013 ◽  
Vol 45 (6) ◽  
pp. 666-672 ◽  
Author(s):  
F. Schneider ◽  
F. Saucy ◽  
R. de Blic ◽  
J. Dai ◽  
F. Mohand ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Rat Model ◽  
Aortic Aneurysms ◽  
Marrow Mesenchymal Stem Cells

Abstract 143: Enrichment of Dimethylation of Lysine 4 on Histone 3 and Resident Vascular Stem Cell Transition to Vascular Smooth Muscle Cells

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Roya Hakimjavadi ◽  
Denise Burtenshaw ◽  
Emma Fitzpatrick ◽  
Mariana Di Luca ◽  
Gillian Casey ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Smooth Muscle ◽  
Stem Cell ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Telomerase Activity ◽  
Histone 3 ◽  
Vascular Stem Cells

Data support a role for stem cell-derived vascular smooth muscle cells (SMC) in arteriosclerosis. Epigenetics play a critical role in SMC differentiation where histone proteins associated with the myosin heavy chain (Myh11) promoter are post-translationally modified by dimethylation of lysine 4 on histone 3 (H3K4me2). Studies report that ‘de-differentiated’ SMC do not exhibit loss of H3K4me2 at the Myh11 promoter even when mRNA levels decrease thereby allowing this modification to be used to track differentiated SMC. Our aim was to determine the level of H3K4me2 and H3K27me3 methylation of differentiated SMCs and compare to resident vascular stem cells and stem cell-derived SMC. Murine adventitial Sca1 + stem cells (APCs), rat medial Sox10 + multipotent vascular stem cells (MVSCs) and CD44 + bone-marrow derived mesenchymal stem cells (MSCs) were all examined for methylation of lysine 4 (H3K4me2) and lysine 27 (H3K27me3) on histone 3 associated with the Myh11 promoter, before and after SMC differentiation and compared to fresh aortic differentiated SMC and sub-cultured de-differentiated SMC in vitro by Chromatin Immunoprecipitation (ChIP) assay. Cells were also examined for Myh11 expression, stemness (telomerase activity) and multipotentcy. Differentiated rat and murine SMC were enriched for H3K4Me2 at the Myh11 promoter, compared to H3K27me3. Phenotypically de-differentiated sub-cutured rat and murine SMC were enriched for H3K4Me2 when compared to H3K27me3, but to a much lesser extent when compared to differentiated aortic SMC. In contrast, resident APCs and MVSCs, and bone-marrow derived MSCs, were all enriched for H3K27me3, concomitant with significant telomerase activity and multipotent differentiation capacity. The levels of enrichment of H3K27me3 dropped significantly after SMC differentiation with TGF-βeta1 concomitant with a significant enrichment of H3K4me2 to levels that mimicked the level of enrichment in de-differentiated SMC when compared to aortic differentiated SMC. De-differentiated SMC exhibit reduced enrichment of H3K4me2 at the Myh11 promoter region when compared to differentiated aortic SMCs, but mimic the level of enrichment of H3K4me2 observed following resident vascular stem cell differentiation to SMCs.

Abstract 573: Vibrational Spectroscopy Discriminates Differentiated Vascular Smooth Muscle Cells From Mesenchymal Stem Cells and Their Vascular Progeny

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Claire Molony ◽  
Mariana Di Luca ◽  
Jennifer McIntyre ◽  
Bryan Hennelly ◽  
Hugh J Byrne ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vibrational Spectroscopy ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Linear Discriminant

Background: The source of intimal vascular smooth muscle cells (SMCs) following vascular remodelling has been controversial, with either de-differentiated SMCs and/or stem cell-derived SMCs playing a putative role. Fourier transform Infrared (FTIR) and Raman spectroscopy are complementary forms of vibrational spectroscopy which provide an excellent platform for extracting important biochemical data in a label-free manner to discriminate cell types. Aim: Determine whether native differentiated SMCs can be distinguished from mesenchymal stem cells (MSCs) and MSC-derived SMCs using vibrational spectroscopy. Methods: Freshly isolated rat aortic differentiated SMCs (up to passage 4), CD44+ bone marrow derived mesenchymal stem cells (MSCs), MSC-derived smooth muscle cells (mdSMCs - after TGF-β1 treatment for 14 d) and osteoblasts (mdOSTs - after osteogenic inductive stimulation for 21 d) were grown and fixed on calcium fluoride slides before their respective spectra were recorded by Raman and FTIR Spectroscopy. Multivariate statistical algorithms, including Principal Components Analysis (PCA) and Linear Discriminant Analysis (LDA), were applied to the spectra in order to classify the cell types based on their biochemical variation. Results: The recorded spectra for each cell type revealed significant visible differences between the cells across all recordings. The PCA score plot discriminated the cells based on their unique characteristics. A combination of PCA-LDA were applied for classification, and a leave one out cross validation resulted in sensitivities and specificities that were >95%. Conclusion: Vibrational spectroscopy discriminates differentiated SMCs from MSC and their vascular progeny and may be useful for identifying these cells as early biomarkers of disease.

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