scholarly journals The Effect of Electrospun Dihydroartemisinin-Loaded Polycaprolactone/Collagen Scaffolds On Osteoblastic Differentiation of Human Adipose-Derived Stem Cells

Author(s):  
nazila shabstani ◽  
Hanieh Mousazdeh ◽  
Fahimeh shyage ◽  
Somayeh Gholami ◽  
Nosratollah Zarghami

In this study, Dihydroartemisinin (DHART)-loaded polycaprolactone collagen nanofibers (PCL/Col NFs) were constructed as effective biocompatible scaffolds through adjusting the proportions of hydrophobic/ hydrophilic polymers for enhanced osteoblastic differentiation of human adipose-derived stem cells (hADSCs). The designed NFs were characterized through FTIR, XRD, TGA, FE-SEM, and tensile testing. DHART-loaded PCL/Col electrospun NFs provide an ideal solution, with the potential of sustained drug release as well as inhibition of drug re-crystallization. Interestingly, inhibiting DHART re-crystallization can improve its bioavailability, providing a more effective therapeutic efficacy. Besides, the data set found through FE-SEM, MTT, PicoGreen, qPCR, and alkaline phosphatase (ALP) assays revealed the improved adhesion and proliferation rate of hADSCs cultured on PCL/Col/DHART (5%) NFs after 14 and 21 days of incubation. These findings confirmed the potential of the designed NF scaffolds for sustained/controlled release of DHART therapeutic molecules toward bone tissue regeneration and engineering.

2016 ◽  
Vol 12 ◽  
pp. 38-47 ◽  
Author(s):  
Aleksandra Skubis ◽  
Bartosz Sikora ◽  
Nikola Zmarzły ◽  
Emilia Wojdas ◽  
Urszula Mazurek

This review article provides an overview on adipose-derived stem cells (ADSCs) for implications in bone tissue regeneration. Firstly this article focuses on mesenchymal stem cells (MSCs) which are object of interest in regenerative medicine. Stem cells have unlimited potential for self-renewal and develop into various cell types. They are used for many therapies such as bone tissue regeneration. Adipose tissue is one of the main sources of mesenchymal stem cells (MSCs). Regenerative medicine intends to differentiate ADSC along specific lineage pathways to effect repair of damaged or failing organs. For further clinical applications it is necessary to understand mechanisms involved in ADSCs proliferation and differentiation. Second part of manuscript based on osteogenesis differentiation of stem cells. Bones are highly regenerative organs but there are still many problems with therapy of large bone defects. Sometimes there is necessary to make a replacement or expansion new bone tissue. Stem cells might be a good solution for this especially ADSCs which manage differentiate into osteoblast in in vitro and in vivo conditions.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Cong Fan ◽  
Xiaohan Ma ◽  
Yuejun Wang ◽  
Longwei Lv ◽  
Yuan Zhu ◽  
...  

Abstract Background MicroRNAs have been recognized as critical regulators for the osteoblastic lineage differentiation of human adipose-derived stem cells (hASCs). Previously, we have displayed that silencing of miR-137 enhances the osteoblastic differentiation potential of hASCs partly through the coordination of lysine-specific histone demethylase 1 (LSD1), bone morphogenetic protein 2 (BMP2), and mothers against decapentaplegic homolog 4 (SMAD4). However, still numerous molecules involved in the osteogenic regulation of miR-137 remain unknown. This study aimed to further elucidate the epigenetic mechanisms of miR-137 on the osteogenic differentiation of hASCs. Methods Dual-luciferase reporter assay was performed to validate the binding to the 3′ untranslated region (3′ UTR) of NOTCH1 by miR-137. To further identify the role of NOTCH1 in miR-137-modulated osteogenesis, tangeretin (an inhibitor of NOTCH1) was applied to treat hASCs which were transfected with miR-137 knockdown lentiviruses, then together with negative control (NC), miR-137 overexpression and miR-137 knockdown groups, the osteogenic capacity and possible downstream signals were examined. Interrelationships between signaling pathways of NOTCH1-hairy and enhancer of split 1 (HES1), LSD1 and BMP2-SMADs were thoroughly investigated with separate knockdown of NOTCH1, LSD1, BMP2, and HES1. Results We confirmed that miR-137 directly targeted the 3′ UTR of NOTCH1 while positively regulated HES1. Tangeretin reversed the effects of miR-137 knockdown on osteogenic promotion and downstream genes expression. After knocking down NOTCH1 or BMP2 individually, we found that these two signals formed a positive feedback loop as well as activated LSD1 and HES1. In addition, LSD1 knockdown induced NOTCH1 expression while suppressed HES1. Conclusions Collectively, we proposed a NOTCH1/LSD1/BMP2 co-regulatory signaling network to elucidate the modulation of miR-137 on the osteoblastic differentiation of hASCs, thus providing mechanism-based rationale for miRNA-targeted therapy of bone defect.


2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Gayathri Subramanian ◽  
Alexander Stasuk ◽  
Mostafa Elsaadany ◽  
Eda Yildirim-Ayan

Adipose-derived mesenchymal stem cells have become a popular cell choice for tendon repair strategies due to their relative abundance, ease of isolation, and ability to differentiate into tenocytes. In this study, we investigated the solo effect of different uniaxial tensile strains and loading frequencies on the matrix directionality and tenogenic differentiation of adipose-derived stem cells encapsulated within three-dimensional collagen scaffolds. Samples loaded at 0%, 2%, 4%, and 6% strains and 0.1 Hz and 1 Hz frequencies for 2 hours/day over a 7-day period using a custom-built uniaxial tensile strain bioreactor were characterized in terms of matrix organization, cell viability, and musculoskeletal gene expression profiles. The results displayed that the collagen fibers of the loaded samples exhibited increased matrix directionality with an increase in strain values. Gene expression analyses demonstrated that ASC-encapsulated collagen scaffolds loaded at 2% strain and 0.1 Hz frequency showed significant increases in extracellular matrix genes and tenogenic differentiation markers. Importantly, no cross-differentiation potential to osteogenic, chondrogenic, and myogenic lineages was observed at 2% strain and 0.1 Hz frequency loading condition. Thus, 2% strain and 0.1 Hz frequency were identified as the appropriate mechanical loading regime to induce tenogenic differentiation of adipose-derived stem cells cultured in a three-dimensional environment.


2016 ◽  
Vol 4 (20) ◽  
pp. 3515-3525 ◽  
Author(s):  
Shirae K. Leslie ◽  
Anthony M. Nicolini ◽  
Gobalakrishnan Sundaresan ◽  
Jamal Zweit ◽  
Barbara D. Boyan ◽  
...  

Alginate microbeads incorporating adipose-derived stem cells (ASCs) have potential for delivering viable cells capable of facilitating tissue regeneration.


2018 ◽  
Vol 19 (12) ◽  
pp. 4095 ◽  
Author(s):  
Emanuela Chiarella ◽  
Annamaria Aloisio ◽  
Stefania Scicchitano ◽  
Valeria Lucchino ◽  
Ylenia Montalcini ◽  
...  

Human adipose-derived stem cells (hADSCs) are multipotent mesenchymal cells that can differentiate into adipocytes, chondrocytes, and osteocytes. During osteoblastogenesis, the osteoprogenitor cells differentiate into mature osteoblasts and synthesize bone matrix components. Zinc finger protein 521 (ZNF521/Zfp521) is a transcription co-factor implicated in the regulation of hematopoietic, neural, and mesenchymal stem cells, where it has been shown to inhibit adipogenic differentiation. The present study is aimed at determining the effects of ZNF521 on the osteoblastic differentiation of hADSCs to clarify whether it can influence their osteogenic commitment. The enforced expression or silencing of ZNF521 in hADSCs was achieved by lentiviral vector transduction. Cells were cultured in a commercial osteogenic medium for up to 20 days. The ZNF521 enforced expression significantly reduced osteoblast development as assessed by the morphological and molecular criteria, resulting in reduced levels of collagen I, alkaline phosphatase, osterix, osteopontin, and calcium deposits. Conversely, ZNF521 silencing, in response to osteoblastic stimuli, induced a significant increase in early molecular markers of osteogenesis and, at later stages, a remarkable enhancement of matrix mineralization. Together with our previous findings, these results show that ZNF521 inhibits both adipocytic and osteoblastic maturation in hADSCs and suggest that its expression may contribute to maintaining the immature properties of hADSCs.


Author(s):  
María Vallet-Regí ◽  
Isabel Izquierdo-Barba ◽  
Montserrat Colilla

This review article describes the importance of structure and functionalization in the performance of mesoporous silica bioceramics for bone tissue regeneration and local drug delivery purposes. Herein, we summarize the pivotal features of mesoporous bioactive glasses, also known as ‘templated glasses’ (TGs), which present chemical compositions similar to those of conventional bioactive sol–gel glasses and the added value of an ordered mesopore arrangement. An in-depth study concerning the possibility of tailoring the structural and textural characteristics of TGs at the nanometric scale and their influence on bioactive behaviour is discussed. The highly ordered mesoporous arrangement of cavities allows these materials to confine drugs to be subsequently released, acting as drug delivery devices. The functionalization of mesoporous silica walls has been revealed as the cornerstone in the performance of these materials as controlled release systems. The synergy between the improved bioactive behaviour and local sustained drug release capability of mesostructured materials makes them suitable to manufacture three-dimensional macroporous scaffolds for bone tissue engineering. Finally, this review tackles the possibility of covalently grafting different osteoinductive agents to the scaffold surface that act as attracting signals for bone cells to promote the bone regeneration process.


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