Stem cells in bone tissue engineering

Seong, Jeong-Min; Kim, Byung-Chul; Park, Jaehong; Kwon, Il Keun; Mantalaris, Anathathios; Hwang, Yu‐Shik

doi:10.1088/1748-6041/5/6/062001

Cited by 184 publications

(159 citation statements)

References 133 publications

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“…Meanwhile, bone marrow MSCs are multipotent cells that have been considered as ideal seed cells in the bone repair. 49 Therefore, the aim in the present study was to evaluate the cell response of obtained PEG/PLA electrospun hybrid scaffolds to MSCs, and the osteogenic development behavior of MSCs cultured on the PEG/PLA electrospun fibrous scaffold in vitro. Surrounding tissue response to the fibrous scaffolds in vivo was also evaluated by transplanting the PEG/PLA electrospun hybrid scaffold into the thigh muscle pouches of rats.…”

Section: Discussionmentioning

confidence: 99%

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

Fu²,

Fan³

et al. 2011

IJN

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Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone tissue engineering application, however, the great hydrophobicity limits its broad application. In this study, the hybrid amphiphilic poly(ethylene glycol) (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with regular and continuous fibers compared to corresponding blank PLA fiber mats. The prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment and proliferation by providing an interconnected porous extracellular environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the interstitial pores and integrate well with the surrounding fibers, which is very important for favorable application in tissue engineering. More importantly, the electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate into bone-associated cells by comprehensively evaluating the representative markers of the osteogenic procedure with messenger ribonucleic acid quantitation and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better differentiation potential with higher messenger ribonucleic acid expression of the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I . The significantly higher alkaline phosphatase activity of the PEG/PLA fibrous scaffolds indicated that these can enhance the differentiation of MSCs into osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level of the late osteogenic differentiation markers OCN ( osteocalcin ) and OPN ( osteopontin ), accompanied by the positive Alizarin red S staining, showed better maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the mineralization stage of differentiation. After transplantation into the thigh muscle pouches of rats, and evaluating the inflammatory cells surrounding the scaffolds and the physiological characteristics of the surrounding tissues, the PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular response and excellent osteogenic potential in vitro, as well as the biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA fibrous scaffolds could be one of the most promising candidates in bone tissue engineering.

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Section: Discussionmentioning

confidence: 99%

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

Fu²,

Fan³

et al. 2011

IJN

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“…The regulation of growth factors and hormones, such as transform growth factor beta (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor 1 (IGF-1), bone morphogenetic protein (BMP) and parathormone (PTH), on MSCs proliferation and differentiation have been studied thoroughly (Haddad and Harb 2005;Qi et al 2009;Huang et al 2010). It has been reported that MSCs cultured in vitro would differentiate into osteoblasts spontaneously (Seong et al 2010;Mikami et al 2011). But whether HIF-1α and Cbfα1 are involved in the proliferation and differentiation of MSCs as well as the osteogenesis-like changes under hypoxia has not been revealed, and also little is known about the regulation of Cbfα1 during the differentiation of MSCs into osteogenic lineage cells.…”

mentioning

confidence: 99%

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

Huang

Deng

Wang

et al. 2011

Tohoku J. Exp. Med.

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Mesenchymal stem sells (MSCs) have received much attention in the field of bone tissue engineering due to their biological capability to differentiate into osteogenic lineage cells. Hypoxia-inducible factor 1alpha (HIF-1α) plays an important role in the MSC-related bone regeneration during hypoxia, while core binding factor alpha 1 (Cbfα1) is a transcription regulator that is involved in the chondrocyte differentiation and ossification. In the present study, we investigated the effects of hypoxia on biological capability of MSCs. MSCs were isolated from adult rabbit bone marrow, and were cultured in vitro under normoxia (air with 5% CO 2 ) or hypoxia (5% CO 2 and 95% N 2 ). The proliferation of MSCs, alkaline phosphatase (ALP) activity, and production of collagens type I and type III (Col I/III) were examined. The expression levels of HIF-1α and Cbfα1 were measured by real-time PCR and western blot analyses. We found that hypoxia significantly induced the proliferation of MSCs and increased ALP activity and the production of Col I/III. Moreover, hypoxia increased the expression of Cbfα1 mRNA after 12 h, whereas the expression of HIF-1α mRNA was increased after 1 h of hypoxia. Knockdown of HIF-1α expression with a small interfering RNA significantly increased the expression levels of Cbfα1 protein either under the normoxia or hypoxia condition. Our results indicate that hypoxia enhances MSCs to differentiate into osteogenic lineage cells and suggest that Cbfα1 may be negatively regulated by HIF-1α.

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“…BMPs belong to the transforming growth factor-beta (TGF-β) superfamily of polypeptides, including TGF-β, activins/inhibins, and BMPs. Specifically, BMP-2 has been demonstrated to induce the differentiation of ADSCs into osteocytes, promote osteogenic differentiation, upregulate bone gene expression after mechanical injury, and improve bone repair after injury (Seong et al, 2010). BMPs bind to specific transmembrane type I and type II receptors and stimulate the intracellular mediators Smad-1, -5, and -8 (Herpin and Cunningham, 2007), which transmit the BMP signal into the nucleus to regulate target gene transcription (Lian et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

BMP-2 promotes chondrogenesis of rat adipose-derived stem cells by using a lentiviral system

Fu¹,

Diao²,

Shao³

et al. 2014

Genet. Mol. Res.

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ABSTRACT. Osteoporosis poses a major public health threat in aging societies. Adipose-derived stem cells (ADSCs) are multipotent adult stem cells that have the ability to yield mesenchymal stem cells, and have the potential to undergo osteogenesis and bone regeneration. Bone morphogenetic proteins (BMPs) have been demonstrated to upregulate bone gene expression after mechanical injury and to improve bone injury repair. This study aimed to produce BMP-2 expression in ADSCs by using lentiviral vectors. Subcutaneous adipose tissue from 4-week-old male Sprague-Dawley rats was used. Oil red O staining was used to detect adipocyte formation from ADSCs. Induction of ADSC osteogenesis was confirmed with Alizarin red S staining. The recombinant lenti-hBMP-2/ BMP-2 promotes chondrogenesis of rat adipose neo was constructed to infect ADSCs, BMP-2 expression was measured by immunoblotting analysis, and cellular alkaline phosphatase levels were examined. We found that >70% of ADSC cells could be induced to differentiate into osteocytes or adipocytes. Under osteogenic induction, ADSCs showed increased intracellular calcium deposition, the formation of calcium tubercles, and the disappearance of cellular structures in calcium tubercles. After infection of ADSCs by lenti-hBMP-2/neo, BMP-2 was expressed after doxycycline induction. We, thus, conclude that ADSCs maintain vigorous growth ex vivo and possess stem celllike properties. When infected with lenti-hBMP-2/neo, ADSCs can be induced to promote BMP-2 expression.

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Stem cells in bone tissue engineering

Cited by 184 publications

References 133 publications

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

Preparation of poly(ethylene glycol)/polylactide hybrid fibrous scaffolds for bone tissue engineering

Hypoxia Induces Osteogenesis-Related Activities and Expression of Core Binding Factor .ALPHA.1 in Mesenchymal Stem Cells

BMP-2 promotes chondrogenesis of rat adipose-derived stem cells by using a lentiviral system

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