Effect of different aged cartilage ECM on chondrogenesis of BMSCs in vitro and in vivo

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.

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Chondrogenic Potential of Dental-Derived Mesenchymal Stromal Cells

Osteology ◽

10.3390/osteology1030016 ◽

2021 ◽

Vol 1 (3) ◽

pp. 149-174

Author(s):

Naveen Jeyaraman ◽

Gollahalli Shivashankar Prajwal ◽

Madhan Jeyaraman ◽

Sathish Muthu ◽

Manish Khanna

Keyword(s):

Tissue Engineering ◽

Mesenchymal Stromal Cells ◽

Tissue Regeneration ◽

Stromal Cells ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Dentin Matrix

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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Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration

NPG Asia Materials ◽

10.1038/s41427-021-00339-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Yunsheng Dong ◽

Yufei Liu ◽

Yuehua Chen ◽

Xun Sun ◽

Lin Zhang ◽

...

Keyword(s):

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Cartilage Defects ◽

In Vivo Experiments ◽

Spatiotemporal Regulation ◽

Stromal Cell Derived Factor ◽

Hydrogel System

AbstractHydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.

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Coculture of hWJMSCs and pACs in Oriented Scaffold Enhances Hyaline Cartilage Regeneration In Vitro

Stem Cells International ◽

10.1155/2019/5130152 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 3

Author(s):

Yu Zhang ◽

Shuyun Liu ◽

Weimin Guo ◽

Chunxiang Hao ◽

Mingjie Wang ◽

...

Keyword(s):

Stem Cells ◽

Articular Cartilage ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Human Umbilical Cord ◽

Cartilage Cells ◽

Collagen Ii ◽

Differentiation Status

Seed cells of articular cartilage tissue engineering face many obstacles in their application because of the dedifferentiation of chondrocytes or unstable chondrogenic differentiation status of pluripotent stem cells. To overcome mentioned dilemmas, a simulation of the articular cartilage microenvironment was constructed by primary articular cartilage cells (pACs) and acellular cartilage extracellular matrix- (ACECM-) oriented scaffold cocultured with human umbilical cord Wharton’s jelly-derived mesenchymal stem cells (hWJMSCs) in vitro. The coculture groups showed more affluent cartilage special matrix ingredients including collagen II and aggrecan based on the results of histological staining and western blotting and cut down as many pACs as possible. The RT-PCR and cell viability experiments also demonstrated that hWJMSCs were successfully induced to differentiate into chondrocytes when cultured in the simulated cartilage microenvironment, as confirmed by the significant upregulation of collagen II and aggrecan, while the cell proliferation activity of pACs was significantly improved by cell-cell interactions. Therefore, compared with monoculture and chondrogenic induction of inducers, coculture providing a simulated native articular microenvironment was a potential and temperate way to regulate the biological behaviors of pACs and hWJMSCs to regenerate the hyaline articular cartilage.

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Biomechanical issues of tissue-engineered constructs for articular cartilage regeneration: in vitro and in vivo approaches

British Medical Bulletin ◽

10.1093/bmb/ldz034 ◽

2019 ◽

Vol 132 (1) ◽

pp. 53-80 ◽

Cited By ~ 2

Author(s):

Lucio Cipollaro ◽

Maria Camilla Ciardulli ◽

Giovanna Della Porta ◽

Giuseppe M Peretti ◽

Nicola Maffulli

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Cartilage Regeneration ◽

Biological Properties ◽

Trophic Factors ◽

Gene Therapies ◽

Zonal Organization ◽

Meta Analyses

Abstract Background Given the limited regenerative capacity of injured articular cartilage, the absence of suitable therapeutic options has encouraged tissue-engineering approaches for its regeneration or replacement. Sources of data Published articles in any language identified in PubMed and Scopus electronic databases up to August 2019 about the in vitro and in vivo properties of cartilage engineered constructs. A total of 64 articles were included following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Areas of agreement Regenerated cartilage lacks the biomechanical and biological properties of native articular cartilage. Areas of controversy There are many different approaches about the development of the architecture and the composition of the scaffolds. Growing points Novel tissue engineering strategies focus on the development of cartilaginous biomimetic materials able to repair cartilage lesions in association to cell, trophic factors and gene therapies. Areas timely for developing research A multi-layer design and a zonal organization of the constructs may lead to achieve cartilage regeneration.

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A novel construct with biomechanical flexibility for articular cartilage regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-019-1399-2 ◽

2019 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Baixiang Cheng ◽

Teng Tu ◽

Xiao Shi ◽

Yanzheng Liu ◽

Ying Zhao ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Hydrostatic Pressure ◽

In Vitro Study ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Temporomandibular Joints ◽

Marrow Mesenchymal Stem Cells

Abstract Background Although tissue-engineered cartilage has been broadly studied, complete integration of regenerated cartilage with residual cartilage is still difficult for the inferior mechanical and biochemical feature of neocartilage. Chondrogenesis of mesenchymal stem cells can be induced by biophysical and biochemical factors. Methods In this study, autologous platelet-rich fibrin (PRF) membrane was used as a growth factor-rich scaffold that may facilitate differentiation of the transplanted bone marrow mesenchymal stem cells (BMSCs). At the same time, hydrostatic pressure was adopted for pre-adjustment of the seed cells before transplantation that may promote the mechanical flexibility of neocartilage. Results An in vitro study showed that the feasible hydrostatic pressure stimulation substantially promoted the chondrogenic potential of in vitro-cultured BMSC/PRF construct. In vivo results revealed that at every time point, the newborn tissues were the most favorable in the pressure-pretreated BMSC/PRF transplant group. Besides, the transplantation of feasible hydrostatic pressure-pretreated construct by BMSC sheet fragments and PRF granules could obviously improve the integration between the regenerated cartilage and host cartilage milieu, and thereby achieve boundaryless repair between the neocartilage and residual host cartilage tissue in rabbit temporomandibular joints. It could be concluded that feasible hydrostatic pressure may effectively promote the proliferation and chondrogenic differentiation of BMSCs in a BMSC/PRF construct. Conclusion This newly formed construct with biomechanical flexibility showed a superior capacity for cartilage regeneration by promoting the mechanical properties and integration of neocartilage.

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

Science Advances ◽

10.1126/sciadv.aaz5913 ◽

2020 ◽

Vol 6 (21) ◽

pp. eaaz5913 ◽

Cited By ~ 1

Author(s):

Junmin Lee ◽

Oju Jeon ◽

Ming Kong ◽

Amr A. Abdeen ◽

Jung-Youn Shin ◽

...

Keyword(s):

Stem Cell ◽

Articular Cartilage ◽

Wnt Signaling Pathway ◽

Cartilage Tissue Engineering ◽

Cartilage Tissue ◽

Tissue Formation ◽

Design Strategies ◽

Rgd Peptides

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.

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Cartilage Tissue Engineering Approaches Need to Assess Fibrocartilage When Hydrogel Constructs Are Mechanically Loaded

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.787538 ◽

2022 ◽

Vol 9 ◽

Author(s):

Hamed Alizadeh Sardroud ◽

Tasker Wanlin ◽

Xiongbiao Chen ◽

B. Frank Eames

Keyword(s):

Tissue Engineering ◽

Collagen Type ◽

Hyaline Cartilage ◽

Imaging Techniques ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

Type I

Chondrocytes that are impregnated within hydrogel constructs sense applied mechanical force and can respond by expressing collagens, which are deposited into the extracellular matrix (ECM). The intention of most cartilage tissue engineering is to form hyaline cartilage, but if mechanical stimulation pushes the ratio of collagen type I (Col1) to collagen type II (Col2) in the ECM too high, then fibrocartilage can form instead. With a focus on Col1 and Col2 expression, the first part of this article reviews the latest studies on hyaline cartilage regeneration within hydrogel constructs that are subjected to compression forces (one of the major types of the forces within joints) in vitro. Since the mechanical loading conditions involving compression and other forces in joints are difficult to reproduce in vitro, implantation of hydrogel constructs in vivo is also reviewed, again with a focus on Col1 and Col2 production within the newly formed cartilage. Furthermore, mechanotransduction pathways that may be related to the expression of Col1 and Col2 within chondrocytes are reviewed and examined. Also, two recently-emerged, novel approaches of load-shielding and synchrotron radiation (SR)–based imaging techniques are discussed and highlighted for future applications to the regeneration of hyaline cartilage. Going forward, all cartilage tissue engineering experiments should assess thoroughly whether fibrocartilage or hyaline cartilage is formed.

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Identifying the Potential of Qur’anic Recitation on the Proliferation of Chondrocytes Derived from Rabbit Articular Cartilage: Work in Progress

IIUM Medical Journal Malaysia ◽

10.31436/imjm.v17i1.1020 ◽

2018 ◽

Vol 17 (1) ◽

Author(s):

Rosyafirah Hashim ◽

Munirah Sha’ban ◽

Sarah Rahmat ◽

Zainul Ibrahim Zainuddin

Keyword(s):

Tissue Engineering ◽

Articular Cartilage ◽

Profile Analysis ◽

Cartilage Tissue Engineering ◽

Cartilage Regeneration ◽

Cartilage Tissue ◽

The Times ◽

And Control ◽

Rabbit Articular Cartilage

Introduction: In Islamic practice, the use of Qur’anic recitation in treatment can be traced back to the times of Prophet Muhammad (PBUH). This preliminary study aims to identify the potential of Qur’anic recitation of Surah Al-Fatihah on the proliferation of chondrocytes derived from rabbit articular cartilage. Cartilage tissue engineering offers an alternative way to facilitate cartilage regeneration in-vitro. Materials and Methods: The cellular model was established using a serially cultured and expanded chondrocytes in-vitro. The model was assigned into three groups. The first group was exposed to the Surah Al-Fatihah, recited 17 times based on the five times daily prayer unit (Raka’ah) obligated upon Muslims. The second group was exposed to an Arabic poem recitation. The third group was not exposed to any sound and served as the control. All groups were subjected to the growth profile analysis. The analysis was conducted at different passages starting from passage 0 to passage 3. Results: The results showed that the cells proliferation based on the growth kinetic analysis is higher for the cells exposed with Qur’anic recitation as compared to the Arabic poem and control groups. Conclusions: The proliferation process of the rabbit articular cartilage might be influenced with the use of Qur’anic recitation and as well as Arabic poem recitation. Exposure to the Western poem recitation and mute sound will be added for future study. It is hoped that this study could shed some light on the potential use of the Qur’anic recitation to facilitate cartilage regeneration in tissue engineering studies.

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Effects of in vitro low oxygen tension preconditioning of buccal fat pad stem cells on in Vivo articular cartilage tissue repair

Life Sciences ◽

10.1016/j.lfs.2021.119728 ◽

2021 ◽

pp. 119728

Author(s):

Fatemeh Dehghani Nazhvani ◽

Leila Mohammadi Amirabad ◽

Arezo Azari ◽

Hamid Namazi ◽

Simzar Hosseinzadeh ◽

...

Keyword(s):

Stem Cells ◽

Articular Cartilage ◽

Tissue Repair ◽

Cartilage Tissue ◽

Low Oxygen ◽

Fat Pad ◽

Buccal Fat Pad ◽

Low Oxygen Tension

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miR-146a-5p Promotes Chondrocyte Apoptosis and Inhibits Autophagy of Osteoarthritis by Targeting NUMB

Cartilage ◽

10.1177/19476035211023550 ◽

2021 ◽

pp. 194760352110235

Author(s):

Hongjun Zhang ◽

Wendi Zheng ◽

Du Li ◽

Jia Zheng

Keyword(s):

Caspase 3 ◽

Cartilage Tissue ◽

Luciferase Reporter ◽

Chondrocyte Apoptosis ◽

Knee Cartilage ◽

Before And After ◽

Related Proteins ◽

Human And Mouse

Objective miR-146a-5p was found to be significantly upregulated in cartilage tissue of patients with osteoarthritis (OA). NUMB was shown to be involved in the autophagy regulation process of cells. We aimed to learn whether NUMB was involved in the apoptosis or autophagy process of chondrocytes in OA and related with miR-146a-5p. Methods QRT-PCR was used to detect miR-146a-5p level in 22 OA cartilage tissues and 22 controls. The targets of miR-146a-5p were analyzed using software and the luciferase reporter experiment. The apoptosis and autophagy, and related proteins were detected in chondrocytes treated with miR-146a-5p mimic/inhibitor or pcDNA3.1-NUMB/si-NUMB and IL-1β, respectively. In vivo experiment, intra-articular injection of miR-146a-5p antagomir/NC was administered at the knee of OA male mice before and after model construction. Chondrocyte apoptosis and the expression of apoptosis and autophagy-related proteins were also detected. Results miR-146a-5p was highly expressed in knee cartilage tissue of patients with OA, while NUMB was lowly expressed and negatively regulated by miR-146a-5p. Upregulation of miR-146a-5p can promote cell apoptosis and reduce autophagy of human and mouse chondrocytes by modulating the levels of cleaved caspase-3, cleaved PARP, Bax, Beclin 1, ATG5, p62, LC3-I, and LC3-II. Increasing the low level of NUMB reversed the effects of miR-146a-5p on chondrocyte apoptosis and autophagy. Intra-articular injection of miR-146a-5p antagomir can also reverse the effects of miR-146a-5p on the apoptosis and autophagy of knee joint chondrocytes in OA mice. Conclusion Downregulation of miR-146a-5p suppresses the apoptosis and promotes autophagy of chondrocytes by targeting NUMB in vivo and in vitro.

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