Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles

Yin, Heyong; Wang, Yu; Sun, Zhen; Sun, Xiaojuan; Xu, Yingbin; Li, Pan; Meng, Hui; Yu, Xiaoming; Xiao, Bo; Fan, Tian; Wang, Yiguo; Xu, Wei; Wang, Aiyuan; Guo, Quanyi; Peng, Jiang; Lu, Shibi

doi:10.1016/j.actbio.2016.01.024

Cited by 113 publications

(97 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…BMPs are members of the TGF-β superfamily of polypeptides. BMPs function by inducing the differentiation of mesenchymal osteoprogenitors to cells of the osteoblastic lineage and by promoting osteoblastic maturation and function [27, 28]. This cellular regulation may be involved in the development of bone and cartilage and in the promotion of healing of fractured bones.…”

Section: Discussionmentioning

confidence: 99%

Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Zhang

Zhao

Zhu

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: The aim of this study was to investigate the influence of Cx43- and Smad-mediated TGF-β/BMP signaling pathway on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into cartilage and inhibition of ossification. Methods: BMSCs of Wistar rats were cultured and assigned into 5 groups for transfection with adenoviruses. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were employed to detect mRNA and protein expressions of target genes. The condition of cartilage and ossification were measured by a series of staining methods. Subcutaneous injection of mesenchymal stem cells (MSCs) into nude rats was performed. Results: After transfection, compared to the AdGFP group, the corresponding target mRNAs were overexpressed in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups, and overexpression of BMP2 at the mRNA and protein expression was observed in the AdSmad1 and AdCx43 + AdSmad1 groups. The mRNA expressions of aggrecan (ACAN) and collagen type II alpha 1 (Col2a1), the glycosaminoglycan content of the extracellular matrix and the expression of type II collagen, Col2a1, osteopontin (OPN) and osteocalcin (OC) were higher in the AdBMP2, AdSmad1, AdCx43 + AdSmad1 and AdCx43 + AdSmad1 + AdBMP2 groups than in the AdGFP group; alkaline phosphatase (ALP) activity and mRNA and protein expressions of Runx2 were also higher in these groups than in the AdGFP group. Heterotopic osteogenesis tests demonstrated evident cartilage differentiation ability in the AdCx43 + AdSmad1 + AdBMP2 groups. In comparison, the AdCx43 + AdSmad1 and AdSmad1 groups exhibited weaker cartilage differentiation abilities. Conclusion: Cx43 and Smad1 promote BMP-induced cartilage differentiation of BMSCs and inhibit osteoblast differentiation, which provide a new strategy for cartilage tissue engineering using exogenous Cx43 and Smad1.

show abstract

Section: Discussionmentioning

confidence: 99%

Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Zhang

Zhao

Zhu

et al. 2017

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…Cell‐seeded dECM particles can be delivered into the defect site as a particle aggregate . Yin et al generated dECM particles from goat articular cartilage.…”

Section: Postdecellularization Processing Methodsmentioning

confidence: 99%

“…Yin et al generated dECM particles from goat articular cartilage. These dECM particles were then seeded with MSCs and aggregated in a rotary cell culture system . Teng et al cultured cartilage‐like tissue by culturing chondrocyte spheroids in suspension in vitro, which were subsequently decellularized and milled into particles .…”

Section: Postdecellularization Processing Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Kim

Majid

Melchiorri

et al. 2018

Bioengineering & Transla Med

255

175

View full text Add to dashboard Cite

Regenerative therapies for bone and cartilage injuries are currently unable to replicate the complex microenvironment of native tissue. There are many tissue engineering approaches attempting to address this issue through the use of synthetic materials. Although synthetic materials can be modified to simulate the mechanical and biochemical properties of the cell microenvironment, they do not mimic in full the multitude of interactions that take place within tissue. Decellularized extracellular matrix (dECM) has been established as a biomaterial that preserves a tissue's native environment, promotes cell proliferation, and provides cues for cell differentiation. The potential of dECM as a therapeutic agent is rising, but there are many limitations of dECM restricting its use. This review discusses the recent progress in the utilization of bone and cartilage dECM through applications as scaffolds, particles, and supplementary factors in bone and cartilage tissue engineering.

show abstract

“…Several therapies have been or are being developed to treat this condition, including cell‐based therapies like autologous chondrocyte implantation and matrix assisted chondrocyte implantation. Stem cells have also been investigated as a cell source, including mesenchymal stem cells (MSCs) and, more recently, chondrocytes differentiated from induced pluripotent stem cells . In all cases, delivery of these cells may be by direct intra‐articular injection or seeded in a scaffold matrix which is then implanted.…”

Section: Introductionmentioning

confidence: 99%

Synthetic Poly(Vinylalcohol)‐Based Membranes for Cartilage Surgery and Repair

Tai

Gao

et al. 2017

Biotechnology Journal

View full text Add to dashboard Cite

Cell-based therapies for cartilage repair are continually being developed to treat osteoarthritis. The cells are either introduced directly by intra-articular injection or via a cell-seeded matrix scaffold. Here, poly(vinylalcohol)-based membranes are developed to be used for mesenchymal stem cell implantation in cartilage repair procedures, having controllable physicochemical properties such as porosity, mechanical strength, and permeability, and a unique self-sealing property. The membranes possess a bilayer structure with a less porous layer providing mechanical strength and selective permeability, exhibit an elastic modulus of between 0.3 and 0.9 MPa, and are permeable to molecules <40 kDa, which is in the range of cartilage permeability. Three different peptide ligands with the sequences Ac-GCGYGRGDSPG, Ac-GCG(OPG)4REGOFG(OPG)4, and Ac-GCG(OPG)7, respectively, are conjugated to the membranes and subject to in vitro cell adhesion and differentiation assays. Col I/Col II gene expression ratios indicated that the collagen-mimetic peptide, Ac-GCG(OPG)7, best supported mesenchymal stem cell differentiation into the chondrogenic lineage. Although low retention of the membrane is observed in vivo in a rabbit knee model, results suggest that the membrane was able to facilitate mesenchymal stem cell implantation and differentiation to chondrocytes. These PVA-based membranes provide a feasible, synthetic, off-the-shelf material for the delivery of stem cells, and can be modified for other surgical applications.

show abstract

Induction of mesenchymal stem cell chondrogenic differentiation and functional cartilage microtissue formation for in vivo cartilage regeneration by cartilage extracellular matrix-derived particles

Cited by 113 publications

References 37 publications

Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Cx43- and Smad-Mediated TGF-β/ BMP Signaling Pathway Promotes Cartilage Differentiation of Bone Marrow Mesenchymal Stem Cells and Inhibits Osteoblast Differentiation

Applications of decellularized extracellular matrix in bone and cartilage tissue engineering

Synthetic Poly(Vinylalcohol)‐Based Membranes for Cartilage Surgery and Repair

Contact Info

Product

Resources

About