Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow and white adipose tissue via Pdgfrα expression

Miwa, Hiroyuki; Era, Takumi

doi:10.1242/dev.155879

Cited by 46 publications

(30 citation statements)

References 65 publications

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“…Bone-marrow derived MSCs (BM-MSCs) and C3H/10T1/2 cells are considered good models of SMC differentiation from mesoderm precursors in vitro 56,57 and single cell autofluorescence emissions clearly discriminated undifferentiated stem cells from their myogenic progeny.…”

Section: Discussionmentioning

confidence: 99%

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Molony

King

Luca

et al. 2020

Preprint

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Background: A hallmark of subclinical atherosclerosis is the accumulation of vascular smooth muscle cell (SMC)-like cells leading to intimal thickening, lipid retention and plaque formation, yet their origin remains controversial. The ability to discriminate heterogeneous populations of cells in the context of various disease processes is of potential clinical and diagnostic value. Methods:The feasibility of multivariate analysis of single cell photonics as a discriminator of cell phenotype was assessed using label-free optical multi-parameter interrogation of single cells on a novel Lab-on-a-Disk (LoaD) platform before myogenic differentiation of a series of multipotent stem cells in vitro, and the cellular heterogeneity within vascular lesions in vivo, was determined using supervised machine learning and validated by genetic lineage tracing in vivo.Findings: Single cell photonics were of sufficient coverage, specificity, and quality to discriminate various disparate cell phenotypes in vitro and normal medial SMCs from SMClike cells following injury ex vivo, in addition to distinguishing myogenic differentiation of a series of multipotent stem cells in vitro. Supervised machine learning of these photonic datasets supported genetic lineage tracing analysis and identified the presence of S100β + stem-derived myogenic progeny within vascular lesions, in part, due to upregulation of Coll 3A1 and elastin.Interpretation: Disease-relevant photonic signatures reflect cell type and differentiation state and may have important predictive value as a phenotypic discriminator for vascular disease. Research in contextEvidence before this study: Cardiovascular disease (CVD), the leading cause of death and disability world-wide is characterized by pathological structural changes to the blood vessel wall. Pathologic observations in humans vessels confirm that early 'transitional' lesions enriched with SMC-like cells are routinely present in atherosclerotic-prone regions of arteries during pathologic intimal thickening, prior to lipid retention, and the appearance of a atherosclerotic plaque. Lineage tracing and single cell RNA sequence analysis (scRNA-seq) analysis has provided compelling evidence for the involvement of differentiated medial SMC and adventitial/medial progenitors derived from SMCs in progressing intimal thickening.Despite these insights, the putative role of resident vascular stem cells that do not originate from medial SMCs in promoting intimal thickening remains controversial. Light as a diagnostic and prognostic tool has several advantages including high sensitivity, non-destructive measurement, small or even non-invasive analysis and low limits of detection for early detection of disease phenotypes. In combination with microfluidics, photonics enables real time measurement of single cells in very small sample volumes. To accompany these photonic platforms, deep learning, a subset of supervised machine learning based primarily on artificial neural network geometries, has rapidly grown as a predictive method t...

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Section: Discussionmentioning

confidence: 99%

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Molony

King

Luca

et al. 2020

Preprint

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“…Mesenchymal stem cells (MSCs) derived from embryonic mesoderm and neuroepithelium can be cultured in vitro to maintain their multipotency or be differentiated into three principle lineages: adipocyte, chondrocyte, and osteocyte [ 1 – 3 ]. In human and mouse adults, MSCs can be isolated from bone marrow, adipose tissue, and several other sites such as vascular pericytes [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cells derived from human iPS cells via mesoderm and neuroepithelium have different features and therapeutic potentials

et al. 2018

Self Cite

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Mesenchymal stem cells (MSCs) isolated from adult human tissues are capable of proliferating in vitro and maintaining their multipotency, making them attractive cell sources for regenerative medicine. However, the availability and capability of self-renewal under current preparation regimes are limited. Induced pluripotent stem cells (iPSCs) now offer an alternative, similar cell source to MSCs. Herein, we established new methods for differentiating hiPSCs into MSCs via mesoderm-like and neuroepithelium-like cells. Both derived MSC populations exhibited self-renewal and multipotency, as well as therapeutic potential in mouse models of skin wounds, pressure ulcers, and osteoarthritis. Interestingly, the therapeutic effects differ between the two types of MSCs in the disease models, suggesting that the therapeutic effect depends on the cell origin. Our results provide valuable basic insights for the clinical application of such cells.

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“…The paraffin sections were also labeled using rabbit monoclonal anti-CD106 antibody (ab134047, Abcam, Cambridge, MA) and goat polyclonal anti-PDGFRα (R&D). PDGFRα and CD106 are known to be expressed in BMMSCs and are commonly used as markers for mesenchymal stem cells (MSCs) [17,18]. The frozen sections were also used for immunohistochemistry and labeled with rabbit polyclonal anti-SDF1 antibody (ab9797, Abcam, Cambridge, MA) and mouse monoclonal CXCR4 antibody (4G10, sc-53534, Santa Cruz Biotechnology).…”

Section: Methodsmentioning

confidence: 99%

The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster

Kido

Miyagawa

Goto

et al. 2018

Preprint

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ObjectivesWe hypothesized that systemic administration of high-mobility group box 1 fragment attenuates the progression of myocardial fibrosis and cardiac dysfunction in a hamster model of dilated cardiomyopathy by recruiting bone marrow mesenchymal stem cells thus causing enhancement of a self-regeneration system.MethodsTwenty-week-old J2N-k hamsters, which are δ-sarcoglycan-deficient, were treated with systemic injection of high-mobility group box 1 fragment (HMGB1, n=15) or phosphate buffered saline (control, n=11). Echocardiography for left ventricular function, cardiac histology, and molecular biology were analyzed. The life-prolonging effect was assessed separately using the HMGB1 and control groups, in addition to a monthly HMGB1 group which received monthly systemic injections of high-mobility group box 1 fragment, 3 times (HMGB1, n=11, control, n=9, monthly HMGB1, n=9).ResultsThe HMGB1 group showed improved left ventricular ejection fraction, reduced myocardial fibrosis, and increased capillary density. The number of platelet-derived growth factor receptor-alpha and CD106 positive mesenchymal stem cells detected in the myocardium was significantly increased, and intra-myocardial expression of tumor necrosis factor α stimulating gene 6, hepatic growth factor, and vascular endothelial growth factor were significantly upregulated after high-mobility group box 1 fragment administration. Improved survival was observed in the monthly HMGB1 group compared with the control group.ConclusionsSystemic high-mobility group box 1 fragment administration attenuates the progression of left ventricular remodeling in a hamster model of dilated cardiomyopathy by enhanced homing of bone marrow mesenchymal stem cells into damaged myocardium, suggesting that high-mobility group box 1 fragment could be a new treatment for dilated cardiomyopathy.

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Tracing the destiny of mesenchymal stem cells from embryo to adult bone marrow and white adipose tissue via Pdgfrα expression

Cited by 46 publications

References 65 publications

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Disease-relevant single cell photonic signatures identify S100β stem cells and their myogenic progeny in vascular lesions

Mesenchymal stem cells derived from human iPS cells via mesoderm and neuroepithelium have different features and therapeutic potentials

The administration of high-mobility group box 1 fragment prevents deterioration of cardiac performance by enhancement of bone marrow mesenchymal stem cell homing in the delta-sarcoglycan-deficient hamster

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