BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells

Mizrahi, Olga; Sheyn, Dmitriy; Tawackoli, Wafa; Kallai, Ilan; Oh, Anthony; Su, Shenping; Da, Xiaoyu; Zarrini, Parham; Cook‐Wiens, Galen; Gazit, Dan; Gazit, Zulma

doi:10.1038/gt.2012.45

Cited by 89 publications

(77 citation statements)

References 52 publications

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“…BMPs are members of the transforming growth factor-β superfamily that are able to induce osteogenic differentiation during embryonic development (11)(12)(13). BMPs exert their biological effects by signaling through two type I serine/threonine kinase receptors, RIA and RIB, which are transduced by Smad1, -4, and -5 transcription factors.…”

Section: Introductionmentioning

confidence: 99%

AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

Battula¹,

Le²,

Sun³

et al. 2017

JCI Insight

110

138

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Section: Introductionmentioning

confidence: 99%

AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

Battula¹,

Le²,

Sun³

et al. 2017

JCI Insight

110

138

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“…172 However, there is some argument concerning the superior osteogenic potential of genetically modified BMSCs compared to that of modified ASCs both in vitro and in vivo. 174 In another study, Schek et al 146 mixed BMP-7 expressing adenovirus with collagen, fibrin, or cell culture medium and implanted them intramuscularly into nude mice. After 4 weeks, radiological and histological analyses showed a superior ability of fibrin glue to deliver the virus.…”

mentioning

confidence: 99%

A review of fibrin and fibrin composites for bone tissue engineering

Noori

Ashrafi

Vaez-Ghaemi

et al. 2017

IJN

377

256

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Tissue engineering has emerged as a new treatment approach for bone repair and regeneration seeking to address limitations associated with current therapies, such as autologous bone grafting. While many bone tissue engineering approaches have traditionally focused on synthetic materials (such as polymers or hydrogels), there has been a lot of excitement surrounding the use of natural materials due to their biologically inspired properties. Fibrin is a natural scaffold formed following tissue injury that initiates hemostasis and provides the initial matrix useful for cell adhesion, migration, proliferation, and differentiation. Fibrin has captured the interest of bone tissue engineers due to its excellent biocompatibility, controllable biodegradability, and ability to deliver cells and biomolecules. Fibrin is particularly appealing because its precursors, fibrinogen, and thrombin, which can be derived from the patient’s own blood, enable the fabrication of completely autologous scaffolds. In this article, we highlight the unique properties of fibrin as a scaffolding material to treat bone defects. Moreover, we emphasize its role in bone tissue engineering nanocomposites where approaches further emulate the natural nanostructured features of bone when using fibrin and other nanomaterials. We also review the preparation methods of fibrin glue and then discuss a wide range of fibrin applications in bone tissue engineering. These include the delivery of cells and/or biomolecules to a defect site, distributing cells, and/or growth factors throughout other pre-formed scaffolds and enhancing the physical as well as biological properties of other biomaterials. Thoughts on the future direction of fibrin research for bone tissue engineering are also presented. In the future, the development of fibrin precursors as recombinant proteins will solve problems associated with using multiple or single-donor fibrin glue, and the combination of nanomaterials that allow for the incorporation of biomolecules with fibrin will significantly improve the efficacy of fibrin for numerous bone tissue engineering applications.

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“…This may be due to the properties of the seeded cells and the scaffold material. A series of assays have shown that the osteogenic potential of BMSCs is greater than that of ASCs both in vitro and in vivo (Mizrahi et al, 2013). Furthermore, our previous studies show that PGS could induce differentiation of bone marrow mononuclear cells to vascular cells and promote vascular tissue formation by adsorbing plasma proteins and platelets Lee et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds

Deng

Bi²,

Zhou³

et al. 2014

eCM

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The repair of critical-sized defects (CSDs) is a significant challenge in bone tissue engineering. Combining the use of progenitor cells with gene therapy represents a promising approach for bone regeneration. MicroRNAs play important roles in most gene regulatory networks, regulate the endogenous expression of multiple growth factors and simultaneously modulate stem cell differentiation. Our previous study showed that knocking down miR-31 promotes the osteogenesis of bone marrow stromal stem cells (BMSCs). To investigate the therapeutic potential of cells engineered to express anti-miR-31 for CSD repair, lentiviral vectors encoding negative control, miR-31 precursor and anti-sense sequences were constructed and transduced into osteo-inductive BMSCs. The expression of osteogenic-specific genes, alkaline phosphatase activity and Alizarin Red S staining were investigated to evaluate the effects of miR-31 on the cell fate of BMSCs over a 3-week period. In addition, miR-31-modified BMSCs seeded on poly(glycerol sebacate) (PGS) scaffolds were used to repair 8 mm critical-sized calvarial defects in rats. The results showed that miR-31 suppression significantly increased the expression of osteogenic-specific genes in vitro at the mRNA and protein levels, and that robust new bone formation with high local bone mineral density was observed in the anti-miR groups in vivo. Moreover, the PGS scaffolds carrying anti-miR-31-expressing BMSCs exhibited good biocompatibility and a high regeneration rate (~60 %) within in vivo bone defects. Our results suggest that miR-31 gene delivery affects the potential of BMSCs for osteogenic differentiation and bone regeneration and that PGS is a potential substrate for genetically modified, tissue-engineered bone in the repair of large bone defects.

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BMP-6 is more efficient in bone formation than BMP-2 when overexpressed in mesenchymal stem cells

Cited by 89 publications

References 52 publications

AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

AML-induced osteogenic differentiation in mesenchymal stromal cells supports leukemia growth

A review of fibrin and fibrin composites for bone tissue engineering

Repair of critical-sized bone defects with anti-miR-31-expressing bone marrow stromal stem cells and poly(glycerol sebacate) scaffolds

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