scholarly journals Effects of TGF-β1 Overexpression on Biological Characteristics of Human Dental Pulp-derived Mesenchymal Stromal Cells

2019 ◽  
Vol 12 (1) ◽  
pp. 170-182 ◽  
Author(s):  
Hasan Salkın ◽  
Zeynep Burçin Gönen ◽  
Ergül Ergen ◽  
Dilek Bahar ◽  
Mustafa Çetin
2017 ◽  
Vol 44 (6) ◽  
pp. 2174-2188 ◽  
Author(s):  
Fangfang Song ◽  
Hualing Sun ◽  
Liyuan Huang ◽  
Dongjie Fu ◽  
Cui Huang

Background/Aims: Human dental pulp-derived mesenchymal stromal cells (hDPSCs) are promising seed cells for tissue engineering due to their easy accessibility and multi-lineage differentiation. Pannexin3 (Panx3) plays crucial roles during bone development and differentiation. The aim of the present study was to investigate the effect of Panx3 on osteogenesis of hDPSCs and the underlying mechanism. Methods: Utilizing qRT-PCR, Western blot, and immunohistochemistry, we explored the change of Panx3 during osteogenic differentiation of hDPSCs. Next, hDPSCs with loss (Panx3 knockdown) and gain (Panx3 overexpression) of Panx3 function were developed to investigate the effects of Panx3 on osteogenic differentiation of hDPSC and the underlying mechanism. Finally, a commercial β-TCP scaffold carrying Panx3-modified hDPSCs was utilized to evaluate bone defect repair. Results: Panx3 was upregulated during osteogenic differentiation in a time-dependent manner. Panx3 overexpression promoted osteogenic differentiation of hDPSCs, whereas depletion of Panx3 resulted in a decline of differentiation, evidenced by upregulated expression of mineralization-related markers, increased alkaline phosphatase (ALP) activity, and enhanced ALP and Alizarin red staining. Panx3 was found to interact with the Wnt/β-catenin signaling pathway, forming a negative feedback loop. However, Wnt/β-catenin did not contribute to enhancement of osteogenic differentiation as observed in Panx3 overexpression. Moreover, Panx3 promoted osteogenic differentiation of hDPSCs via increasing ERK signaling pathway. Micro-CT and histological staining results showed that Panx3-modified hDPSCs significantly improved ossification of critical-sized bone defects. Conclusion: These findings suggest that Panx3 is a crucial modulator of hDPSCs differentiation.


2014 ◽  
Vol 18 (2) ◽  
pp. 344-354 ◽  
Author(s):  
Anoop Babu Vasandan ◽  
Shilpa Rani Shankar ◽  
Priya Prasad ◽  
Vulugundam Sowmya Jahnavi ◽  
Ramesh Ramachandra Bhonde ◽  
...  

2021 ◽  
Vol 22 (10) ◽  
pp. 5224
Author(s):  
Kenny Man ◽  
Liam Lawlor ◽  
Lin-Hua Jiang ◽  
Xuebin B. Yang

The use of human dental pulp stromal cells (hDPSCs) has gained increasing attention as an alternative stem cell source for bone tissue engineering. The modification of the cells’ epigenetics has been found to play an important role in regulating differentiation, with the inhibition of histone deacetylases 3 (HDAC3) being linked to increased osteogenic differentiation. This study aimed to induce epigenetic reprogramming using the HDAC2 and 3 selective inhibitor, MI192 to promote hDPSCs osteogenic capacity for bone regeneration. MI192 treatment caused a time–dose-dependent change in hDPSC morphology and reduction in viability. Additionally, MI192 successfully augmented hDPSC epigenetic functionality, which resulted in increased histone acetylation and cell cycle arrest at the G2/M phase. MI192 pre-treatment exhibited a dose-dependent effect on hDPSCs alkaline phosphatase activity. Quantitative PCR and In-Cell Western further demonstrated that MI192 pre-treatment significantly upregulated hDPSCs osteoblast-related gene and protein expression (alkaline phosphatase, bone morphogenic protein 2, type I collagen and osteocalcin) during osteogenic differentiation. Importantly, MI192 pre-treatment significantly increased hDPSCs extracellular matrix collagen production and mineralisation. As such, for the first time, our findings show that epigenetic reprogramming with the HDAC2 and 3 selective inhibitor MI192 accelerates the osteogenic differentiation of hDPSCs, demonstrating the considerable utility of this MSCs engineering approach for bone augmentation strategies.


2020 ◽  
Vol 23 (12) ◽  
pp. 870-879
Author(s):  
Kosar Mohamed Ali ◽  
Fattah Hama Rahim Fattah ◽  
Shirwan Hamasalh Omar ◽  
Mohammed I M Gubari ◽  
Mahmoud Yousefifard ◽  
...  

Background: A definitive conclusion on the efficacy of mesenchymal stromal cells-derived conditioned medium (MSCs-CM) in pulmonary fibrosis has not yet been reached. Therefore, the present meta-analysis intends to investigate the efficacy of MSCs-CM administration on improvement of pulmonary fibrosis. Methods: An extensive search was performed on the Medline, Embase, Scopus and Web of Science databases by the end of August 2019. Outcomes in the present study included pulmonary fibrosis score, lung collagen deposition, lung collagen expression, transforming growth factor β1 (TGF-β1) expression and interleukin-6 expression. Finally, the data were pooled and an overall standardized mean difference (SMD) with a 95% confidence interval (CI) was reported. Results: Data from seven studies were included. Analyses showed that administration of MSCs-CM significantly improved pulmonary fibrosis (SMD = -2.36; 95% CI: -3.21, -1.51). MSCs-CM administration also attenuated lung collagen deposition (SMD = -1.70; 95% CI: -2.18, -1.23) and decreased expression of type I collagen (SMD = -6.27; 95% CI: -11.00, -1.55), type III collagen (SMD = -5.16; 95% CI: -9.86, -0.47), TGF- β1 (SMD = -3.36; 95% CI: - 5.62, -1.09) and interleukin-6 (SMD = -1.69; 95% CI: - 3.14, -0.24). Conclusion: The present meta-analysis showed that administration of MSCs-CM improves pulmonary fibrosis. It seems that the effect of MSCs-CM was mediated by reducing collagen deposition as well as inhibiting the production of inflammatory chemokines such as TGF-β1 and interleukin 6 (IL-6). Since there is no evidence on the efficacy of MSCs-CM in large animals, further studies are needed to translate the finding to clinical studies.


Micron ◽  
2014 ◽  
Vol 67 ◽  
pp. 155-168 ◽  
Author(s):  
Serena Barachini ◽  
Serena Danti ◽  
Simone Pacini ◽  
Delfo D’Alessandro ◽  
Vittoria Carnicelli ◽  
...  

2002 ◽  
Vol 43 (2) ◽  
pp. 387-390 ◽  
Author(s):  
K. Dobie ◽  
G. Smith ◽  
A. J. Sloan ◽  
A. J. Smith

2019 ◽  
Vol 47 (4) ◽  
pp. 470-477
Author(s):  
Hany Aly ◽  
Yasmeen Mansi ◽  
Zahraa Ez El Din ◽  
Hala Gabr Metwally ◽  
Amira Sabry

Abstract Background The pathogenesis of bronchopulmonary dysplasia (BPD) includes arrest of alveolar septation and enhanced fibrosis. We hypothesized that mesenchymal stromal cells (MSC) and transforming growth factor-β1 (TGF-β1) in tracheal aspirates of mechanically ventilated premature infants differ in BPD and non-BPD infants. Methods Tracheal aspirates were collected during the first week of life. Mononuclear cells were separated, cultured and immunophenotyped by flow cytometry. MSCs colony/cluster ratio was calculated as an index for dysplastic potentials. TGF-β1 was assessed by enzyme-linked immunosorbent assay (ELISA). Setting: Neonatal intensive care unit. Patients Premature infants at risk for BPD. Results A total of 121 preterm infants were enrolled; 27 of them died and among the 94 survivors 23 infants had BPD. MSCs were identified in younger [gestational age (GA): 30.9±1.7 vs. 31.8±1.8, P=0.025] and smaller [birth weight (BW): 1.3±0.28 vs. 1.44±0.37 kg, P=0.04] infants with lower Apgar scores. The recovery rate of MSCs in BPD and non-BPD groups did not differ. BPD group had significantly smaller colony/cluster ratio compared to non-BPD (0.97 vs. 4.25, P=0.002). TGF-β1 was significantly greater in BPD infants (4173.9±864.3 vs. 3705.8±540.5 pg/mL, P=0.021). Conclusion Infants with BPD had different MSCs morphology and greater TGF-β1 expression. The pathogenesis for these morphological changes of resident lung MSCs needs further studying.


Cytokine ◽  
2007 ◽  
Vol 40 (1) ◽  
pp. 44-51 ◽  
Author(s):  
Virve Pääkkönen ◽  
Jussi Vuoristo ◽  
Tuula Salo ◽  
Leo Tjäderhane

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