Extracellular Matrix Molecule-Based Capture of Mesenchymal Stromal Cells Under Flow

2017 ◽  
pp. 249-260
Author(s):  
Teresa Massam-Wu ◽  
Stuart A. Cain ◽  
Cay M. Kielty
Keyword(s):  
Extracellular Matrix ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Matrix Molecule ◽  
Extracellular Matrix Molecule

scholarly journals The Extracellular Matrix Molecule Hyaluronic Acid Regulates Hippocampal Synaptic Plasticity by Modulating Postsynaptic L-Type Ca2+ Channels

Neuron ◽  
2010 ◽  
Vol 67 (1) ◽  
pp. 116-128 ◽  
Author(s):  
Gaga Kochlamazashvili ◽  
Christian Henneberger ◽  
Olena Bukalo ◽  
Elena Dvoretskova ◽  
Oleg Senkov ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Hyaluronic Acid ◽  
Synaptic Plasticity ◽  
Matrix Molecule ◽  
Hippocampal Synaptic Plasticity ◽  
Extracellular Matrix Molecule ◽  
Ca2 Channels

scholarly journals Exogenous Delivery of Link N mRNA into Chondrocytes and MSCs—The Potential Role in Increasing Anabolic Response

2019 ◽  
Vol 20 (7) ◽  
pp. 1716 ◽  
Author(s):  
Gauri Tendulkar ◽  
Sabrina Ehnert ◽  
Vrinda Sreekumar ◽  
Tao Chen ◽  
Hans-Peter Kaps ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Intervertebral Disc ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Cell Types ◽  
Bmp Signaling ◽  
Anabolic Response ◽  
Health And Social Care ◽  
Intervertebral Disc Regeneration ◽  
Exogenous Delivery

Musculoskeletal disorders, such as osteoarthritis and intervertebral disc degeneration are causes of morbidity, which concomitantly burdens the health and social care systems worldwide, with massive costs. Link N peptide has recently been described as a novel anabolic stimulator for intervertebral disc repair. In this study, we analyzed the influence on anabolic response, by delivering synthetic Link N encoding mRNA into primary human chondrocytes and mesenchymal stromal cells (SCP1 cells), Furthermore, both cell types were seeded on knitted titanium scaffolds, and the influence of Link N peptide mRNA for possible tissue engineering applications was investigated. Synthetic modified Link N mRNA was efficiently delivered into both cell types and cell transfection resulted in an enhanced expression of aggrecan, Sox 9, and type II collagen with a decreased expression of type X collagen. Interestingly, despite increased expression of BMP2 and BMP7, BMP signaling was repressed and TGFβ signaling was boosted by Link N transfection in mesenchymal stromal cells, suggesting possible regulatory mechanisms. Thus, the exogenous delivery of Link N peptide mRNA into cells augmented an anabolic response and thereby increased extracellular matrix synthesis. Considering these findings, we suppose that the cultivation of cells on knitted titanium scaffolds and the exogenous delivery of Link N peptide mRNA into cells could mechanically support the stability of tissue-engineered constructs and improve the synthesis of extracellular matrix by seeded cells. This method can provide a potent strategy for articular cartilage and intervertebral disc regeneration.

scholarly journals Rho/ROCK Inhibition Promotes TGF-β3-Induced Tenogenic Differentiation in Mesenchymal Stromal Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Michaela Melzer ◽  
Susanna Schubert ◽  
Simon Franz Müller ◽  
Joachim Geyer ◽  
Alina Hagen ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Actin Cytoskeleton ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Nuclear Translocation ◽  
Signalling Molecules ◽  
Tenogenic Differentiation ◽  
Extracellular Matrix Components ◽  
Matrix Components ◽  
Rock Inhibition

Mesenchymal stromal cells (MSC) represent a promising therapeutic tool for tendon regeneration. Their tenogenic differentiation is crucial for tissue engineering approaches and may support their beneficial effects after cell transplantation in vivo. The transforming growth factor (TGF)-β, signalling via intracellular Smad molecules, is a potent paracrine mediator of tenogenic induction. Moreover, scaffold topography or tendon matrix components induced tenogenesis via activation of the Rho/ROCK cascade, which, however, is also involved in pathological adaptations in extracellular matrix pathologies. The aim of this study was to investigate the interplay of Rho/ROCK and TGF-β3/Smad signalling in tenogenic differentiation in both human and equine MSC. Primary equine and human MSC isolated from adipose tissue were cultured as monolayers or on tendon-derived decellularized scaffolds to evaluate the influence of the ROCK inhibitor Y-27632 on TGF-β3-induced tenogenic differentiation. The MSC were incubated with and without TGF-β3 (10 ng/ml), Y-27632 (10 μM), or both. On day 1 and day 3, the signalling pathway of TGF-β and the actin cytoskeleton were visualized by Smad 2/3 and phalloidin staining, and gene expression of signalling molecules and tendon markers was assessed. ROCK inhibition was confirmed by disruption of the actin cytoskeleton. Activation of Smad 2/3 with nuclear translocation was evident upon TGF-β3 stimulation. Interestingly, this effect was most pronounced with additional ROCK inhibition in both species ( p < 0.05 in equine MSC). In line with that, the tendon marker scleraxis showed the strongest upregulation when TGF-β3 and ROCK inhibition were combined ( p < 0.05 in human MSC). The regulation pattern of tendon extracellular matrix components and the signalling molecules TGF-β3 and Smad 8 showed differences between human and equine MSC. The obtained results showed that ROCK inhibition promotes the TGF-β3/Smad 2/3 axis, with possible implications for future MSC priming regimes in tendon therapy.

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