scholarly journals Combinatorial screening of biochemical and physical signals for phenotypic regulation of stem cell–based cartilage tissue engineering

2020 ◽  
Vol 6 (21) ◽  
pp. eaaz5913 ◽  
Author(s):  
Junmin Lee ◽  
Oju Jeon ◽  
Ming Kong ◽  
Amr A. Abdeen ◽  
Jung-Youn Shin ◽  
...  

Despite great progress in biomaterial design strategies for replacing damaged articular cartilage, prevention of stem cell-derived chondrocyte hypertrophy and resulting inferior tissue formation is still a critical challenge. Here, by using engineered biomaterials and a high-throughput system for screening of combinatorial cues in cartilage microenvironments, we demonstrate that biomaterial cross-linking density that regulates matrix degradation and stiffness—together with defined presentation of growth factors, mechanical stimulation, and arginine-glycine-aspartic acid (RGD) peptides—can guide human mesenchymal stem cell (hMSC) differentiation into articular or hypertrophic cartilage phenotypes. Faster-degrading, soft matrices promoted articular cartilage tissue formation of hMSCs by inducing their proliferation and maturation, while slower-degrading, stiff matrices promoted cells to differentiate into hypertrophic chondrocytes through Yes-associated protein (YAP)–dependent mechanotransduction. in vitro and in vivo chondrogenesis studies also suggest that down-regulation of the Wingless and INT-1 (WNT) signaling pathway is required for better quality articular cartilage-like tissue production.

2020 ◽  
Vol 7 (6) ◽  
pp. 583-595
Author(s):  
Xiuyu Wang ◽  
Yan Lu ◽  
Wan Wang ◽  
Qiguang Wang ◽  
Jie Liang ◽  
...  

Abstract Extracellular matrix (ECM)-based biomaterials are promising candidates in cartilage tissue engineering by simulating the native microenvironment to regulate the chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) without exogenous growth factors. The biological properties of ECM scaffolds are primarily depended on the original source, which would directly influence the chondrogenic effects of the ECM materials. Despite the expanding investigations on ECM scaffolds in recent years, the selection of optimized ECM materials in cartilage regeneration was less reported. In this study, we harvested and compared the articular cartilage ECM from newborn, juvenile and adult rabbits. The results demonstrated the significant differences in the mechanical strength, sulphated glycosaminoglycan and collagen contents of the different aged ECM, before and after decellularization. Consequently, different compositional and mechanical properties were shown in the three ECM-based collagen hydrogels, which exerted age-dependent chondrogenic inducibility. In general, both in vitro and in vivo results suggested that the newborn ECM promoted the most chondrogenesis of BMSCs but led to severe matrix calcification. In contrast, BMSCs synthesized the lowest amount of cartilaginous matrix with minimal calcification with adult ECM. The juvenile ECM achieved the best overall results in promoting chondrogenesis of BMSCs and preventing matrix calcification. Together, this study provides important information to our current knowledge in the design of future ECM-based biomaterials towards a successful repair of articular cartilage.


2007 ◽  
Vol 342-343 ◽  
pp. 385-388
Author(s):  
So Eun Lee ◽  
Young Mee Jung ◽  
Soo Hyun Kim ◽  
Sang Heon Kim ◽  
Jong Won Rhie ◽  
...  

In cartilage tissue engineering, as a cell source, adult stem cells are very attractive for clinical applications. Recent studies suggest that human adipose tissue-derived stromal cells (ASCs) have multilineage potential similar to bone marrow-derived stromal cells (BMSCs). ASCs are obtained from adipose tissue easily isolated by suction-assisted lipectomy in various body parts. Also, as one of major factors of cartilage tissue engineering, scaffolds have an important role in cartilage formation. Poly(L-lactide-co-ε-carprolactone) scaffolds have physiological activity, biodegradability, high cell affinity, and mechano-activity. The object of this study is cartilaginous tissue formation using highly elastic PLCL scaffolds and ASCs in vitro and in vivo. Poly(L-lactide-co-ε-carprolactone) copolymers were synthesized from lactide and ε-carprolactone in the presence of stannous octoate as catalyst. The scaffolds with 85% porosity and 300-500μm pore size were fabricated by gel-pressing method. ASCs were seeded on scaffolds and cultured for 21days in vitro. Cell/polymer constructs were characterized by reverse transcriptase-polymerase chain reaction for confirming differentiation to chondrocytes onto PLCL scaffolds. Also, for examining cartilaginous tissue formation in vivo, ASCs seeded scaffolds which were induced chondrogenesis for 2 weeks were implanted in nude mice subcutaneously for up to 8weeks. Histological studies showed that implants partially developed cartilaginous tissue within lacunae. And there was an accumulation of sulfated glycoaminoglycans. Immunohistochemical analysis revealed that implants were positively stained for specific extracellular matrix. These results indicate that ASCs and PLCL scaffols could be used to cartilage tissue engineering.


Life Sciences ◽  
2021 ◽  
pp. 119728
Author(s):  
Fatemeh Dehghani Nazhvani ◽  
Leila Mohammadi Amirabad ◽  
Arezo Azari ◽  
Hamid Namazi ◽  
Simzar Hosseinzadeh ◽  
...  

2009 ◽  
Vol 21 (03) ◽  
pp. 149-155 ◽  
Author(s):  
Hsu-Wei Fang

Cartilage injuries may be caused by trauma, biomechanical imbalance, or degenerative changes of joint. Unfortunately, cartilage has limited capability to spontaneous repair once damaged and may lead to progressive damage and degeneration. Cartilage tissue-engineering techniques have emerged as the potential clinical strategies. An ideal tissue-engineering approach to cartilage repair should offer good integration into both the host cartilage and the subchondral bone. Cells, scaffolds, and growth factors make up the tissue engineering triad. One of the major challenges for cartilage tissue engineering is cell source and cell numbers. Due to the limitations of proliferation for mature chondrocytes, current studies have alternated to use stem cells as a potential source. In the recent years, a lot of novel biomaterials has been continuously developed and investigated in various in vitro and in vivo studies for cartilage tissue engineering. Moreover, stimulatory factors such as bioactive molecules have been explored to induce or enhance cartilage formation. Growth factors and other additives could be added into culture media in vitro, transferred into cells, or incorporated into scaffolds for in vivo delivery to promote cellular differentiation and tissue regeneration.Based on the current development of cartilage tissue engineering, there exist challenges to overcome. How to manipulate the interactions between cells, scaffold, and signals to achieve the moderation of implanted composite differentiate into moderate stem cells to differentiate into hyaline cartilage to perform the optimum physiological and biomechanical functions without negative side effects remains the target to pursue.


2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Mohammed Zayed ◽  
Steven Newby ◽  
Nabil Misk ◽  
Robert Donnell ◽  
Madhu Dhar

Horses are widely used as large animal preclinical models for cartilage repair studies, and hence, there is an interest in using equine synovial fluid-derived mesenchymal stem cells (SFMSCs) in research and clinical applications. Since, we have previously reported that similar to bone marrow-derived MSCs (BMMSCs), SFMSCs may also exhibit donor-to-donor variations in their stem cell properties; the current study was carried out as a proof-of-concept study, to compare the in vivo potential of equine BMMSCs and SFMSCs in articular cartilage repair. MSCs from these two sources were isolated from the same equine donor. In vitro analyses confirmed a significant increase in COMP expression in SFMSCs at day 14. The cells were then encapsulated in neutral agarose scaffold constructs and were implanted into two mm diameter full-thickness articular cartilage defect in trochlear grooves of the rat femur. MSCs were fluorescently labeled, and one week after treatment, the knee joints were evaluated for the presence of MSCs to the injured site and at 12 weeks were evaluated macroscopically, histologically, and then by immunofluorescence for healing of the defect. The macroscopic and histological evaluations showed better healing of the articular cartilage in the MSCs’ treated knee than in the control. Interestingly, SFMSC-treated knees showed a significantly higher Col II expression, suggesting the presence of hyaline cartilage in the healed defect. Data suggests that equine SFMSCs may be a viable option for treating osteochondral defects; however, their stem cell properties require prior testing before application.


2006 ◽  
Vol 49 ◽  
pp. 189-196
Author(s):  
Soo Hyun Kim ◽  
Young Mee Jung ◽  
Sang Heon Kim ◽  
Young Ha Kim ◽  
Jun Xie ◽  
...  

To engineer cartilaginous constructs with a mechano-active scaffold and dynamic compression was performed for effective cartilage tissue engineering. Mechano-active scaffolds were fabricated from very elastic poly(L-lactide-co-ε-carprolactone)(5:5). The scaffolds with 85 % porosity and 300~500 μm pore size were prepared by a gel-pressing method. The scaffolds were seeded with chondrocytes and the continuous compressive deformation of 5% strain was applied to cell-polymer constructs with 0.1Hz to evaluate for the effect of dynamic compression for regeneration of cartilage. Also, the chondrocytes-seeded constructs stimulated by the continuous compressive deformation of 5% strain with 0.1Hz for 10 days and 24 days respectively were implanted in nude mice subcutaneously to investigate their biocompatibility and cartilage formation. From biochemical analyses, chondrogenic differentiation was sustained and enhanced significantly and chondrial extracellular matrix was increased through mechanical stimulation. Histological analysis showed that implants stimulated mechanically formed mature and well-developed cartilaginous tissue, as evidenced by chondrocytes within lacunae. Masson’s trichrome and Safranin O staining indicated an abundant accumulation of collagens and GAGs. Also, ECM in constructs was strongly immuno-stained with anti-rabbit collagen type II antibody. Consequently, the periodic application of dynamic compression can improve the quality of cartilaginous tissue formed in vitro and in vivo.


2010 ◽  
Vol 16 (1) ◽  
pp. 343-353 ◽  
Author(s):  
João T. Oliveira ◽  
Tírcia C. Santos ◽  
Luís Martins ◽  
Ricardo Picciochi ◽  
Alexandra P. Marques ◽  
...  

2006 ◽  
Vol 39 ◽  
pp. S447
Author(s):  
S. Tiwari ◽  
S. Pollok ◽  
H. Notbohm ◽  
R. Reis ◽  
B. Vollmar ◽  
...  

Osteology ◽  
2021 ◽  
Vol 1 (3) ◽  
pp. 149-174
Author(s):  
Naveen Jeyaraman ◽  
Gollahalli Shivashankar Prajwal ◽  
Madhan Jeyaraman ◽  
Sathish Muthu ◽  
Manish Khanna

The field of tissue engineering has revolutionized the world in organ and tissue regeneration. With the robust research among regenerative medicine experts and researchers, the plausibility of regenerating cartilage has come into the limelight. For cartilage tissue engineering, orthopedic surgeons and orthobiologists use the mesenchymal stromal cells (MSCs) of various origins along with the cytokines, growth factors, and scaffolds. The least utilized MSCs are of dental origin, which are the richest sources of stromal and progenitor cells. There is a paradigm shift towards the utilization of dental source MSCs in chondrogenesis and cartilage regeneration. Dental-derived MSCs possess similar phenotypes and genotypes like other sources of MSCs along with specific markers such as dentin matrix acidic phosphoprotein (DMP) -1, dentin sialophosphoprotein (DSPP), alkaline phosphatase (ALP), osteopontin (OPN), bone sialoprotein (BSP), and STRO-1. Concerning chondrogenicity, there is literature with marginal use of dental-derived MSCs. Various studies provide evidence for in-vitro and in-vivo chondrogenesis by dental-derived MSCs. With such evidence, clinical trials must be taken up to support or refute the evidence for regenerating cartilage tissues by dental-derived MSCs. This article highlights the significance of dental-derived MSCs for cartilage tissue regeneration.


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