scholarly journals Endometriotic Peritoneal Fluid Promotes Myofibroblast Differentiation of Endometrial Mesenchymal Stem Cells

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Zhenzhen Zhang ◽  
Luxuan Suo ◽  
Yabing Chen ◽  
Li Zhu ◽  
Guiping Wan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Peritoneal Fluid ◽  
Type I Collagen ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Collagen I ◽  
Type I ◽  
Myofibroblast Differentiation ◽  
Alpha Smooth Muscle Actin

During the development of endometriosis, the presence of fibrotic tissues in and surrounding endometriotic lesions may lead to subsequent adhesion, anatomic distortion, and chronic pain. Therefore, studies aimed at clarifying the underlying mechanisms of fibrogenesis in endometriosis could potentially provide a novel strategy for effective treatment. Mesenchymal stem cells (MSCs) play a key role in fibrotic diseases by differentiating into myofibroblasts in appropriate microenvironment. In this study, we collected endometrial and endometriotic tissues from patients with endometriosis (n=32) and control patients without endometriosis (n=20) to compare the expression of fibrotic proteins and investigate the effect of endometriotic peritoneal fluid (PF) on myofibroblast differentiation of endometrial MSCs. We found that the expression of fibrotic proteins, including alpha-smooth muscle actin (α-SMA), type I collagen (collagen I), connective tissue growth factor (CTGF), and fibronectin, and the extent of fibrosis extremely enhanced in ectopic endometria compared with eutopic endometria from the same patients with endometriosis and normal endometria from patients without endometriosis. We next isolated and identified endometrial MSCs and found that treatment with endometriotic PF strongly induced endometrial MSCs to differentiate into myofibroblasts concomitant with the activation of Smad2/3. Moreover, ectopic endometrial MSCs expressed elevated collagen I, α-SMA, fibronectin, and CTGF. Sushi domain containing-2 (SUSD2), a marker of endometrial MSCs, and α-SMA, a well-recognized marker for myofibroblasts, colocalized extensively in ectopic endometria while seldom in normal and eutopic endometria. These findings suggest that ectopic endometrial MSCs are probably more susceptible to myofibroblast differentiation because of the long-term influence of endometriotic PF. All together, we report for the first time that endometriotic PF promotes myofibroblast differentiation of endometrial MSCs. This understanding will greatly improve our understanding of the pathophysiology of endometriosis and help design better therapeutics.

scholarly journals The AP-1 Transcription Factor Fosl-2 Regulates Autophagy in Cardiac Fibroblasts during Myocardial Fibrogenesis

2021 ◽  
Vol 22 (4) ◽  
pp. 1861
Author(s):  
Jemima Seidenberg ◽  
Mara Stellato ◽  
Amela Hukara ◽  
Burkhard Ludewig ◽  
Karin Klingel ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Type I Collagen ◽  
Transforming Growth Factor ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Beclin 1 ◽  
Type I ◽  
Alpha Smooth Muscle Actin

Background: Pathological activation of cardiac fibroblasts is a key step in development and progression of cardiac fibrosis and heart failure. This process has been associated with enhanced autophagocytosis, but molecular mechanisms remain largely unknown. Methods and Results: Immunohistochemical analysis of endomyocardial biopsies showed increased activation of autophagy in fibrotic hearts of patients with inflammatory cardiomyopathy. In vitro experiments using mouse and human cardiac fibroblasts confirmed that blockade of autophagy with Bafilomycin A1 inhibited fibroblast-to-myofibroblast transition induced by transforming growth factor (TGF)-β. Next, we observed that cardiac fibroblasts obtained from mice overexpressing transcription factor Fos-related antigen 2 (Fosl-2tg) expressed elevated protein levels of autophagy markers: the lipid modified form of microtubule-associated protein 1A/1B-light chain 3B (LC3BII), Beclin-1 and autophagy related 5 (Atg5). In complementary experiments, silencing of Fosl-2 with antisense GapmeR oligonucleotides suppressed production of type I collagen, myofibroblast marker alpha smooth muscle actin and autophagy marker Beclin-1 in cardiac fibroblasts. On the other hand, silencing of either LC3B or Beclin-1 reduced Fosl-2 levels in TGF-β-activated, but not in unstimulated cells. Using a cardiac hypertrophy model induced by continuous infusion of angiotensin II with osmotic minipumps, we confirmed that mice lacking either Fosl-2 (Ccl19CreFosl2flox/flox) or Atg5 (Ccl19CreAtg5flox/flox) in stromal cells were protected from cardiac fibrosis. Conclusion: Our findings demonstrate that Fosl-2 regulates autophagocytosis and the TGF-β-Fosl-2-autophagy axis controls differentiation of cardiac fibroblasts. These data provide a new insight for the development of pharmaceutical targets in cardiac fibrosis.

APPLICATION OF DENDRIMER/PLASMID hBMP-2 COMPLEXES LOADED INTO β-TCP/COLLAGEN SCAFFOLD IN THE TREATMENT OF FEMORAL DEFECTS IN RATS

2014 ◽  
Vol 26 (01) ◽  
pp. 1450005 ◽  
Author(s):  
Tingwei Bao ◽  
Huiming Wang ◽  
Wentao Zhang ◽  
Xuefeng Xia ◽  
Jiabei Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
Cell Attachment ◽  
Collagen Scaffold ◽  
Bone Defects ◽  
Bone Morphogenetic Protein 2 ◽  
Porous Scaffolds ◽  
Type I

Purpose: Plasmid loading into scaffolds to enhance sustained release of growth factors is an important focus of regenerative medicine. The aim of this study was to build gene-activated matrices (GAMs) and examine the bone augmentation properties. Methods: Generation 5 polyamidoamine dendrimers (G5 dPAMAM)/plasmid recombinant human bone morphogenetic protein-2 (rhBMP-2) complexes were immobilized into beta-tricalcium phosphate (β-TCP)/type I collagen porous scaffolds. After cultured with rat mesenchymal stem cells (rMSCs), transfection efficiencies were examined. The secretion of rhBMP-2 and alkaline phosphatase (ALP) were detected to evaluate the osteogenic properties. Scanning electron microscopy (SEM) was used to observe attachment and proliferation. Moreover, we applied these GAMs directly into freshly created segmental bone defects in rat femurs, and their osteogenic efficiencies were evaluated. Results: Released plasmid complexes were transfected into stem cells and were expressed, which caused osteogenic differentiations of rat mesenchymal stem cells (rMSCs). SEM analysis showed excellent cell attachment. Bioactivity of plasmid rhBMP-2 was maintained in vivo, and the X-ray observation, histological analysis and immunohistochemistry (IHC) of bone tissue demonstrated that the bone healing in segmental femoral defects was enhanced by implantation of GAMs. Conclusions: Such biomaterials offer therapeutic opportunities in critical-sized bone defects.

Type I collagen promotes proliferation and osteogenesis of human mesenchymal stem cells via activation of ERK and Akt pathways

2010 ◽  
Vol 9999A ◽  
pp. NA-NA ◽  
Author(s):  
Kuo-Shu Tsai ◽  
Shou-Yen Kao ◽  
Chien-Yuan Wang ◽  
Yng-Jiin Wang ◽  
Jung-Pan Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
Human Mesenchymal Stem Cells ◽  
Type I

Alpha-smooth muscle actin expression and structure integrity in chondrogenesis of human mesenchymal stem cells

2006 ◽  
Vol 324 (3) ◽  
pp. 457-466 ◽  
Author(s):  
Shih-Chieh Hung ◽  
Pei-Yin Kuo ◽  
Ching-Fang Chang ◽  
Tain-Hsiung Chen ◽  
Larry Low-Tone Ho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Actin ◽  
Human Mesenchymal Stem Cells ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Actin Expression

scholarly journals Promotion of Hepatic Differentiation of Bone Marrow Mesenchymal Stem Cells on Decellularized Cell-Deposited Extracellular Matrix

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hongliang He ◽  
Xiaozhen Liu ◽  
Liang Peng ◽  
Zhiliang Gao ◽  
Yun Ye ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Extracellular Matrix ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Type I Collagen ◽  
Type Iii Collagen ◽  
Type I ◽  
Hepatic Differentiation ◽  
Marrow Mesenchymal Stem Cells

Interactions between stem cells and extracellular matrix (ECM) are requisite for inducing lineage-specific differentiation and maintaining biological functions of mesenchymal stem cells by providing a composite set of chemical and structural signals. Here we investigated if cell-deposited ECM mimickedin vivoliver's stem cell microenvironment and facilitated hepatogenic maturation. Decellularization process preserved the fibrillar microstructure and a mix of matrix proteins in cell-deposited ECM, such as type I collagen, type III collagen, fibronectin, and laminin that were identical to those found in native liver. Compared with the cells on tissue culture polystyrene (TCPS), bone marrow mesenchymal stem cells (BM-MSCs) cultured on cell-deposited ECM showed a spindle-like shape, a robust proliferative capacity, and a suppressed level of intracellular reactive oxygen species, accompanied with upregulation of two superoxide dismutases. Hepatocyte-like cells differentiated from BM-MSCs on ECM were determined with a more intensive staining of glycogen storage, an elevated level of urea biosynthesis, and higher expressions of hepatocyte-specific genes in contrast to those on TCPS. These results demonstrate that cell-deposited ECM can be an effective method to facilitate hepatic maturation of BM-MSCs and promote stem-cell-based liver regenerative medicine.

TGF-β Enhances the Integrin α2β1-Mediated Attachment of Mesenchymal Stem Cells to Type I Collagen

2010 ◽  
Vol 19 (5) ◽  
pp. 645-656 ◽  
Author(s):  
Katrin Warstat ◽  
Diana Meckbach ◽  
Michaela Weis-Klemm ◽  
Anita Hack ◽  
Gerd Klein ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
Type I

scholarly journals Age-Dependent Expression of Collagen Receptors and Deformation of Type I Collagen Substrates by Rat Cardiac Fibroblasts

2011 ◽  
Vol 17 (4) ◽  
pp. 555-562 ◽  
Author(s):  
Christopher G. Wilson ◽  
John W. Stone ◽  
Vennece Fowlkes ◽  
Mary O. Morales ◽  
Catherine J. Murphy ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Type I Collagen ◽  
Cardiac Fibroblasts ◽  
Smooth Muscle Actin ◽  
Type I ◽  
Β1 Integrin ◽  
Alpha Smooth Muscle Actin ◽  
Collagen Receptors ◽  
Age Dependent ◽  
Adult Cells

AbstractLittle is known about how age influences the ways in which cardiac fibroblasts interact with the extracellular matrix. We investigated the deformation of collagen substrates by neonatal and adult rat cardiac fibroblasts in monolayer and three-dimensional (3D) cultures, and quantified the expression of three collagen receptors [discoidin domain receptor (DDR)1, DDR2, and β1 integrin] and the contractile protein alpha smooth muscle actin (α-SMA) in these cells. We report that adult fibroblasts contracted 3D collagen substrates significantly less than their neonate counterparts, whereas no differences were observed in monolayer cultures. Adult cells had lower expression of β1 integrin and α-SMA than neonate cultures, and we detected significant correlations between the expression of α-SMA and each of the collagen receptors in neonate cells but not in adult cells. Consistent with recent work demonstrating age-dependent interactions with myocytes, our results indicate that interactions between cardiac fibroblasts and the extracellular matrix change with age.

scholarly journals 3D Biomimetic Scaffold for Growth Factor Controlled Delivery: An In-Vitro Study of Tenogenic Events on Wharton’s Jelly Mesenchymal Stem Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1448
Author(s):  
Maria Camilla Ciardulli ◽  
Joseph Lovecchio ◽  
Pasqualina Scala ◽  
Erwin Pavel Lamparelli ◽  
Tina Patricia Dale ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Type I Collagen ◽  
In Vitro Study ◽  
Wharton’S Jelly ◽  
Controlled Delivery ◽  
Type I ◽  
Wharton's Jelly

The present work described a bio-functionalized 3D fibrous construct, as an interactive teno-inductive graft model to study tenogenic potential events of human mesenchymal stem cells collected from Wharton’s Jelly (hWJ-MSCs). The 3D-biomimetic and bioresorbable scaffold was functionalized with nanocarriers for the local controlled delivery of a teno-inductive factor, i.e., the human Growth Differentiation factor 5 (hGDF-5). Significant results in terms of gene expression were obtained. Namely, the up-regulation of Scleraxis (350-fold, p ≤ 0.05), type I Collagen (8-fold), Decorin (2.5-fold), and Tenascin-C (1.3-fold) was detected at day 14; on the other hand, when hGDF-5 was supplemented in the external medium only (in absence of nanocarriers), a limited effect on gene expression was evident. Teno-inductive environment also induced pro-inflammatory, (IL-6 (1.6-fold), TNF (45-fold, p ≤ 0.001), and IL-12A (1.4-fold)), and anti-inflammatory (IL-10 (120-fold) and TGF-β1 (1.8-fold)) cytokine expression upregulation at day 14. The presented 3D construct opens perspectives for the study of drug controlled delivery devices to promote teno-regenerative events.

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