The role of bFGF in down-regulating α-SMA expression of chondrogenically induced BMSCs and preventing the shrinkage of BMSC engineered cartilage

Li, Qiong; Liu, Tianyi; Zhang, Lu; Yu, Liang; Zhang, Wenjie; Liu, Wei; Cao, Yilin; Zhou, Guangdong

doi:10.1016/j.biomaterials.2011.03.020

Cited by 35 publications

(15 citation statements)

References 33 publications

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“…40 However, studies involving MSCs reveal that bFGF antagonizes SMC marker expression 10 Some investigators have shown that bFGF in the presence of TGFb1 reduces aSMA expression in MSCs that are differentiated toward a chondrogenic lineage. 41,42 All these factors could have possibly resulted in the dedifferentiation of SMCs cultured in the bioreactor and further resulted in the expression of the ''off-target'' markers that we observed in some of our cultures. These results highlight the importance of engineering the microenvironment of differentiated stem cells to maintain a stable lineage commitment.…”

Section: Discussionmentioning

confidence: 93%

Small diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells

Sundaram

Echter²,

Sivarapatna³

et al. 2013

Tissue Engineering Part A

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Despite the progress made thus far in the generation of small-diameter vascular grafts, cell sourcing still remains a problem. Human embryonic stem cells (hESCs) present an exciting new cell source for the regeneration applications due to their high proliferative and differentiation capabilities. In this study, the feasibility of creating small-diameter vascular constructs using smooth muscle cells (SMCs) differentiated from hESCderived mesenchymal cells was evaluated. In vitro experiments confirmed the ability of these cells to differentiate into smooth muscle actin-and calponin-expressing SMCs in the presence of known inducers, such as transforming growth factor beta. Human vessel walls were constructed by culturing these cells in a bioreactor system under pulsatile conditions for 8 weeks. Histological analysis showed that vessel grafts had similarities to their native counterparts in terms of cellularity and SMC marker expression. However, markers of cartilage and bone tissue were also detected, thus raising questions about stable lineage commitment during differentiation and calling for more stringent analysis of differentiating cell populations.

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Section: Discussionmentioning

confidence: 93%

Small diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells

Sundaram

Echter²,

Sivarapatna³

et al. 2013

Tissue Engineering Part A

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“…The avascularity of tissue-engineered cartilage from differentiated BMSCs is important for its clinical application. In addition, the results of our study showed that shrinkage and deformation often occurred during in vitro chondrogenic induction of large BMSC-scaffold constructs [Li et al, 2011]. However, mature chondrocytes were well able to preserve the phenotypic stability of ectopic transplants; moreover, seeding of chondrocytes on the scaffold could produce a certain shape of cartilage in vivo, such as the shape of a human ear or trachea [Vacanti et al, 1994;Cao et al, 1997].…”

Section: Introductionmentioning

confidence: 86%

“…However, TGF-β is an essential growth factor for BMSC chondrogenesis in vitro, and shrinkage of BMSC-engineered tissue is inevitable in chondrogenesis. Li et al [2011] showed that basic fibroblast growth factor could repress α-SMA expression caused by chondrogenic induction, effectively preventing shrinkage of BMSC-engineered tissue, and had a positive effect on cartilage formation. In our study, in the one-step construction and in the first step of the two-step construction method, after chondrogenic induction for 8 weeks, BMSC-engineered cartilage shrunk to a certain degree.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, two-step construction avoided the shrinkage commonly observed in BMSC-engineered cartilage. Studies have shown that large sizes of BMSC-engineered tissue tend to shrink and deform during chondrogenic induction and fail to accurately maintain their original shape and size, which obviously limits their application in repairing cartilage defects with specific shapes, such as auricular and nasal defects, and upregulation of expression of smooth muscle actin-α (α-SMA), one of the main proteins that cause cell contraction, by TGF-β in chondrogenic induction is probably one of the main underlying reasons for shrinkage of BMSC-engineered cartilage in vitro [Li et al, 2011]. Narita et al [2008] demonstrated that TGF-β could markedly upregulate α-SMA expression in BMSCs.…”

Section: Discussionmentioning

confidence: 99%

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A Two-Step Method of Constructing Mature Cartilage Using Bone Marrow-Derived Mesenchymal Stem Cells

Xue

Zhou³

et al. 2013

Cells Tissues Organs

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Bone marrow-derived mesenchymal stem cells (BMSCs) are a promising source of stem cells for tissue engineering in cartilage repair. However, construction of cartilage using BMSCs can involve many problems, such as fibrosis, vascularization, the ‘hollow' phenomenon and shrinkage, which may be caused by the incomplete differentiation of BMSCs and prevent the clinical application of tissue-engineered cartilage. A novel induction system that facilitates chondrogenesis by swine BMSCs has been developed. In this study, we constructed cartilage using a two-step procedure: first, promoting complete chondrogenic differentiation of BMSCs in 8 weeks, and second, these chondrocytes which differentiated from BMSCs in vitro were provided with a three-dimensional scaffold, which was then implanted subcutaneously. The results indicate that this two-step construction procedure can promote the full chondrogenic differentiation of BMSCs in vitro and the formation of mature ectopic cartilage by BMSCs in vivo.

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“…Next, samples were fixed (n = 3), embedded in paraffin, and cut into 5-μm sections, which were then stained with haematoxylin and eosin (HE), Safranin-O (SO), COL II (monoclonal antibody ab34712, 1:100, Abcam, Cambridge, UK), COL I (monoclonal antibody 600-401-104 S, 1:100, Rockland, PA) and COL X (monoclonal antibody ab49945, 1:100, Abcam, Cambridge, UK), according to our previously established methods4748.…”

Section: Methodsmentioning

confidence: 99%

Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model

Liu

Luo

et al. 2017

Sci Rep

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Functional reconstruction of large osteochondral defects is always a major challenge in articular surgery. Some studies have reported the feasibility of repairing articular osteochondral defects using bone marrow stromal cells (BMSCs) and biodegradable scaffolds. However, no significant breakthroughs have been achieved in clinical translation due to the instability of in vivo cartilage regeneration based on direct cell-scaffold construct implantation. To overcome the disadvantages of direct cell-scaffold construct implantation, the current study proposed an in vitro cartilage regeneration strategy, providing relatively mature cartilage-like tissue with superior mechanical properties. Our strategy involved in vitro cartilage engineering, repair of osteochondral defects, and evaluation of in vivo repair efficacy. The results demonstrated that BMSC engineered cartilage in vitro (BEC-vitro) presented a time-depended maturation process. The implantation of BEC-vitro alone could successfully realize tissue-specific repair of osteochondral defects with both cartilage and subchondral bone. Furthermore, the maturity level of BEC-vitro had significant influence on the repaired results. These results indicated that in vitro cartilage regeneration using BMSCs is a promising strategy for functional reconstruction of osteochondral defect, thus promoting the clinical translation of cartilage regeneration techniques incorporating BMSCs.

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The role of bFGF in down-regulating α-SMA expression of chondrogenically induced BMSCs and preventing the shrinkage of BMSC engineered cartilage

Cited by 35 publications

References 33 publications

Small diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells

Small diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells

A Two-Step Method of Constructing Mature Cartilage Using Bone Marrow-Derived Mesenchymal Stem Cells

Repair of osteochondral defects with in vitro engineered cartilage based on autologous bone marrow stromal cells in a swine model

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