Fibronectin and stem cell differentiation – lessons from chondrogenesis

Singh, Purva; Schwarzbauer, Jean E.

doi:10.1242/jcs.095786

Cited by 163 publications

(158 citation statements)

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“…The ECM is an intricate network of proteins surrounding cells and performs a central function in establishing the stem cell phenotype. The composition and mechanical properties of the ECM can affect cell shape and stem cell differentiation (36). The predominant fibrillar components of the ECM can be divided into two groups: Collagens and cell-adhesive glycoproteins (e.g.…”

Section: Discussionmentioning

confidence: 99%

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

Dong

Qing-shen

et al. 2016

Molecular Medicine Reports

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Abstract. Mesenchymal stem cells (MSCs) are an attractive cellular source for cell-based therapy, tissue engineering and regenerative medicine. However, the use of MSCs is limited by their low incorporation rate in the graft environment. The majority of cells are lost from the graft within 1 month, due to reduced microenvironment or local inflammation at the graft site. The extracellular matrix (ECM) may assist the survival and expansion of MSCs. The present study aimed to identify an effective approach to increase ECM expression levels by MSCs in order to enhance the therapeutic effect and survival rate of MSCs at the injury site. The concentration-dependent effect of transforming growth factor (TGF)-β1 on human umbilical cord (hUC)-MSC proliferation and expression of ECM genes was investigated. MSCs were successfully isolated, cultured and expanded from hUC. A low concentration of TGF-β1 (0.1 ng/ml) exhibited the optimal effect on hUC-MSC proliferation and markedly stimulated the expression of ECM genes, particularly fibronectin (FN). Furthermore, treatment with TGF-β1 caused no alteration in the immunophenotype and differentiation capacity of MSCs. In vivo experiments in rats demonstrated that intravenous injection of control UC-MSCs or TGF-β1-pre-treated UC-MSCs reduced the severity of lipopolysaccharide-induced lung injury, assessed using histology, measurements of the wet-dry lung weight ratio, and neutrophil count and protein concentration in bronchoalveolar lavage fluid. However, the short-term (48 h) therapeutic effects of untreated and TGF-β1-pre-treated UC-MSCs were similar. The survival of MSCs in damaged lungs, determined by Sry gene expression levels, were significantly increased in MSCs pre-treated with TGF-β1. In conclusion, pre-treatment of MSCs with a low concentration of TGF-β1 enhanced the expression of ECM components, particularly FN, thus, improving the survival and potential therapeutic benefits of MSCs. Pre-treatment of MSCs with TGF-β1 may prolong the effective therapy time and represent an efficient therapeutic approach for tissue repair.

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Section: Discussionmentioning

confidence: 99%

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

Dong

Qing-shen

et al. 2016

Molecular Medicine Reports

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“…Differentiated chondrocytes can follow two fates: one is to continue to proliferate and maintain a cartilaginous structure and function, the second is to undergo hypertrophy. Hypertrophic chondrocytes undergo apoptosis leaving behind a mineralized matrix that acts as a template for osteoblasts (Lefebvre and Bhattaram, 2010;Singh and Schwarzbauer, 2012;Sundelacruz and Kaplan, 2009). One of the key features of chondrogenesis is a temporal change in the composition of the deposited ECM .…”

Section: Introductionmentioning

confidence: 99%

“…Upregulation of the cell-cell adhesion proteins N-cadherin and neural cell adhesion molecule (N-CAM) is a hallmark of condensing cells (Bobick et al, 2009;Singh and Schwarzbauer, 2012) and condensation is reduced with loss of N-cadherin function (Bobick et al, 2009;DeLise and Tuan, 2002a;DeLise and Tuan, 2002b). Among the matrix proteins, fibronectin is abundant in mesenchyme and is upregulated during condensation in vivo and in vitro (Dessau et al, 1980;Kulyk et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…Interactions involving the N-terminal domain of fibronectin and heparinase-sensitive molecules on mesenchymal cell surfaces have been implicated in condensation (Frenz et al, 1989). Fibronectin is a ubiquitous ECM protein that is assembled into a fibrillar matrix through a cell-mediated process, and links cells with collagens and other ECM proteins (Kadler et al, 2008;Singh and Schwarzbauer, 2012). However, an essential role for fibronectin matrix assembly during precartilage condensation has not been demonstrated.…”

Section: Introductionmentioning

confidence: 99%

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Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

Singh

Schwarzbauer

2014

Journal of Cell Science

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Mesenchymal cell condensation is the initiating event in endochondral bone formation. Cell condensation is followed by differentiation into chondrocytes, which is accompanied by induction of chondrogenic gene expression. Gene mutations involved in chondrogenesis cause chondrodysplasias and other skeletal defects. Using mesenchymal stem cells (MSCs) in an in vitro chondrogenesis assay, we found that knockdown of the diastrophic dysplasia (DTD) sulfate transporter (DTDST, also known as SLC26A2), which is required for normal cartilage development, blocked cell condensation and caused a significant reduction in fibronectin matrix. Knockdown of fibronectin with small interfering RNAs (siRNAs) also blocked condensation. Fibrillar fibronectin matrix was detected prior to cell condensation, and its levels increased during and after condensation. Inhibition of fibronectin matrix assembly by use of the functional upstream domain (FUD) of adhesin F1 from Streptococcus pyogenes prevented cell condensation by MSCs and also by the chondrogenic cell line ATDC5. Our data show that cell condensation and induction of chondrogenesis depend on fibronectin matrix assembly and DTDST, and indicate that this transporter is required earlier in chondrogenesis than previously appreciated. They also raise the possibility that certain of the skeletal defects in DTD patients might derive from the link between DTDST, fibronectin matrix and condensation.

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“…Next, bone osteoprogenitors and the cartilagenous matrix are replaced by the mineralized matrix [16]. Another significant event is the change in fibronectin expression, as three different isoforms of this glycoprotein emerge [17]. The most suitable markers of the stages in this process are the various collagen types, with expression of type I, III and V collagens specifically marking condensation of the mesenchymal cells.…”

Section: +mentioning

confidence: 99%

The role of growth factors in stem cell-directed chondrogenesis: a real hope for damaged cartilage regeneration

Augustyniak

Trzeciak

Richter

et al. 2014

International Orthopaedics (SICOT)

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Purpose The use of stem cells in regenerative medicine offers hope to treat numerous orthopaedic disorders, including articular cartilage defects. Although much research has been carried out on chondrogenesis, this complicated process is still not well understood and much more research is needed. The present review provides an overview of the stages of chondrogenesis and describes the effects of various growth factors, which act during the multiple steps involved in stem celldirected differentiation towards chondrocytes. Methods The current literature on stem cell-directed chondrogenesis, in particular the role of members of the transforming growth factor-β (TGF-β) superfamily-TGF-βs, bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs)-is reviewed and discussed. Results Numerous studies have reported the chondrogenic potential of both adult-and embryonic-like stem cells and the role of growth factors in programming differentiation of these cells towards chondrocytes. Mesenchymal stem cells (MSCs) are adult multipotent stem cells, whereas induced pluripotent stem cells (iPSC) are reprogrammed pluripotent cells. Although better understanding of the processes involved in the development of cartilage tissues is necessary, both cell types may be of value in the clinical treatment of cartilage injuries or osteoarthritic cartilage lesions. Conclusions MSCs and iPSCs both present unique characteristics. However, at present, it is still unclear which cell type is most suitable in the treatment of cartilage injuries.

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Fibronectin and stem cell differentiation – lessons from chondrogenesis

Cited by 163 publications

References 132 publications

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

Low levels of TGF-β1 enhance human umbilical cord-derived mesenchymal stem cell fibronectin production and extend survival time in a rat model of lipopolysaccharide-induced acute lung injury

Fibronectin matrix assembly is essential for cell condensation during chondrogenesis

The role of growth factors in stem cell-directed chondrogenesis: a real hope for damaged cartilage regeneration

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