scholarly journals Development of Hydrogel with Anti-Inflammatory Properties Permissive for the Growth of Human Adipose Mesenchymal Stem Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
R. Sánchez-Sánchez ◽  
E. Martínez-Arredondo ◽  
V. Martínez-López ◽  
Y. Melgarejo-Ramírez ◽  
A. Brena-Molina ◽  
...  

Skin wound repair requires the development of different kinds of biomaterials that must be capable of restoring the damaged tissue. Type I collagen and chitosan have been widely used to develop scaffolds for skin engineering because of their cell-related signaling properties such as proliferation, migration, and survival. Collagen is the major component of the skin extracellular matrix (ECM), while chitosan mimics the structure of the native polysaccharides and glycosaminoglycans in the ECM. Chitosan and its derivatives are also widely used as drug delivery vehicles since they are biodegradable and noncytotoxic. Regulation of the inflammatory response is crucial for wound healing and tissue regeneration processes; and, consequently, the development of biomaterials such as hydrogels with anti-inflammatory properties is very important and permissive for the growth of cells. In the last years, it has been shown that mesenchymal stem cells have clinical importance in the treatment of different pathologies, for example, skin injuries. In this paper, we describe the anti-inflammatory activity of collagen type 1/chitosan/dexamethasone hydrogel, which is permissive for the culture of human adipose-derived mesenchymal stem cells (hADMSC). Our results show that hADMSC cultured in the hydrogel are viable, proliferate, and secrete the anti-inflammatory cytokine interleukin-10 (IL-10) but not the inflammatory cytokine Tumor Necrosis Factor-alpha (TNF-α).

2014 ◽  
Vol 26 (01) ◽  
pp. 1450005 ◽  
Author(s):  
Tingwei Bao ◽  
Huiming Wang ◽  
Wentao Zhang ◽  
Xuefeng Xia ◽  
Jiabei Zhou ◽  
...  

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.


2010 ◽  
Vol 9999A ◽  
pp. NA-NA ◽  
Author(s):  
Kuo-Shu Tsai ◽  
Shou-Yen Kao ◽  
Chien-Yuan Wang ◽  
Yng-Jiin Wang ◽  
Jung-Pan Wang ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Hongliang He ◽  
Xiaozhen Liu ◽  
Liang Peng ◽  
Zhiliang Gao ◽  
Yun Ye ◽  
...  

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.


2010 ◽  
Vol 19 (5) ◽  
pp. 645-656 ◽  
Author(s):  
Katrin Warstat ◽  
Diana Meckbach ◽  
Michaela Weis-Klemm ◽  
Anita Hack ◽  
Gerd Klein ◽  
...  

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1448
Author(s):  
Maria Camilla Ciardulli ◽  
Joseph Lovecchio ◽  
Pasqualina Scala ◽  
Erwin Pavel Lamparelli ◽  
Tina Patricia Dale ◽  
...  

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.


Author(s):  
A. I. Stukan ◽  
I. V. Gilevich ◽  
V. A. Porhanov ◽  
V. N. Bodnya

Acute respiratory disease COVID-19 caused by the SARS-CoV-2 coronavirus demonstrate weak clinical manifestation in most patients. However, pneumonia and acute respiratory distress syndrome in some cases may cause serious problems due to the lack of effective etiotropic and pathogenetic therapy. Presumably, SARS-CoV-2 leads to the delayed type I interferon activation and loss of control over virus replication in the early stages of infection, which is why the adaptive CD8+T-cell response must be controlled to avoid the development of pulmonary pathology. These data should be taken into account when developing strategies for COVID-19 therapy. Mesenchymal stem cells therapy serves as possible treatment opportunity for severe forms of the disease due to their homing, pronounced anti-inflammatory and antifibrotic properties. It was found that in viral infections, including COVID-19, mesenchymal stem cells can synthesize antiviral defense mediators under the influence of interferon causing resistance to viruses. Thus, mesenchymal stem cells are able to provide comprehensive anti-inflammatory protection, which leads to clinical improvement in patients with COVID-19.


2021 ◽  
Vol 22 (24) ◽  
pp. 13594
Author(s):  
Luis Oliveros Anerillas ◽  
Paul J. Kingham ◽  
Mikko J. Lammi ◽  
Mikael Wiberg ◽  
Peyman Kelk

Autologous bone transplantation is the principal method for reconstruction of large bone defects. This technique has limitations, such as donor site availability, amount of bone needed and morbidity. An alternative to this technique is tissue engineering with bone marrow-derived mesenchymal stem cells (BMSCs). In this study, our aim was to elucidate the benefits of culturing BMSCs in 3D compared with the traditional 2D culture. In an initial screening, we combined BMSCs with four different biogels: unmodified type I collagen (Col I), type I collagen methacrylate (ColMa), an alginate and cellulose-based bioink (CELLINK) and a gelatin-based bioink containing xanthan gum (GelXA-bone). Col I was the best for structural integrity and maintenance of cell morphology. Osteogenic, adipogenic, and chondrogenic differentiations of the BMSCs in 2D versus 3D type I collagen gels were investigated. While the traditional pellet culture for chondrogenesis was superior to our tested 3D culture, Col I hydrogels (i.e., 3D) favored adipogenic and osteogenic differentiation. Further focus of this study on osteogenesis were conducted by comparing 2D and 3D differentiated BMSCs with Osteoimage® (stains hydroxyapatite), von Kossa (stains anionic portion of phosphates, carbonates, and other salts) and Alizarin Red (stains Ca2+ deposits). Multivariate gene analysis with various covariates showed low variability among donors, successful osteogenic differentiation, and the identification of one gene (matrix metallopeptidase 13, MMP13) significantly differentially expressed in 2D vs. 3D cultures. MMP13 protein expression was confirmed with immunohistochemistry. In conclusion, this study shows evidence for the suitability of type I collagen gels for 3D osteogenic differentiation of BMSCs, which might improve the production of tissue-engineered constructs for treatment of bone defects.


2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Timothy Cashman ◽  
Irene C Turnbull ◽  
Ioannis Karakikes ◽  
Jose Da Silva ◽  
Joshua M Hare ◽  
...  

Mesenchymal stem cells (MSC) have demonstrated efficacy for improving cardiomyocyte (CM) function in vitro, in vivo and in clinical trials, but the mechanism of this enhancement remains elusive. The objective of this study was to test the hypothesis that human engineered cardiac tissues (hECT) offer a viable model system to investigate the effects of human MSC on CM contractile function. Human CM (hCM) were produced from embryonic stem cells (hESC, H7 line) using a small-molecule based differentiation approach. Blebbistatin and BMP4 were added to hESC suspended in StemPro34 differentiation media for 24 h, followed by BMP4 and Activin A to day 4.5, followed by addition of IWR-1 Wnt inhibitor for at least 4 days. To create hECT, approximately 1 million hCM were mixed with 2.0 mg/ml bovine type I collagen and 0.9 mg/ml Matrigel, and pipetted into a mold fabricated from polydimethylsiloxane with integrated cantilever end-posts. To model hMSC cell therapy, two types of hECT were created: hCM-only control hECT, and hMSC-CM hybrid hECT containing hCM mixed with 5-10% of human bone marrow-derived MSC. Over several days in culture, the hECT self-assembled and started beating; end-post deflection was tracked in real time to compute twitch force using beam theory. Human CMs were produced with high efficiency (>70% cTnT+) with a predominantly ventricular phenotype (MLC2v+). Resulting hECTs exhibited spontaneous beating (1.3±0.4 Hz), cellular alignment, registered sarcomeres, and expression of cardiac specific genes cTnT, α-MHC, β-MHC and SERCA2a. After 11±2 days in culture, developed stress (force/area) was over 10-fold higher in hMSC-CM hybrid tissues (0.27±0.048 mN/mm 2 ) compared to hCM-only controls (0.02±0.006 mN/mm 2 ; p=0.04, n=5 per group). This reflected significantly greater twitch force (0.11±0.004 mN vs 0.033±0.016 mN, p=0.016) and smaller cross-sectional area (0.19±0.12 mm 2 vs 0.49±0.10 mm 2 ; p=0.003) in hMSC-CM hybrid vs hCM-only hECT. In conclusion, human ECT offer a novel system to study MSC-CM interactions. The findings suggest hMSC supplementation improves contractility compared to CM-only hECT. Investigating the mechanisms of hMSC-mediated enhancement of hECT function may yield insights into MSC-based therapies for cardiac regeneration.


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