The development of tissue-engineered bone of different origin through endochondral and intramembranous ossification following the implantation of mesenchymal stem cells and osteoblasts in a murine model

Tortelli, Federico; Tasso, Roberta; Loiacono, Fabrizio; Cancedda, Ranieri

doi:10.1016/j.biomaterials.2009.09.038

Cited by 129 publications

(117 citation statements)

References 30 publications

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“…Ectopic models are relatively simple, less costly and less invasive. For example, ectopic bone formation models were recently used to elucidate whether the maturation status of implanted cells determines the origin of tissue-engineered bone [105] and to demonstrate new bone formation after the implantation of the OSTEOGROW device (rhBMP6 in autologous blood coagulum) without any signs of inflammation or fibrosis [17]. Although successfully used as a preliminary model for screening various formulations of osteogenic cells, scaffolds and growth factors, the ectopic model displays serious limitations including the eventual reabsorption of newly formed bone and the lack of effective mechanical stimulus required for bone remodelling [106].…”

Section: Animal Model Considerationsmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

130

116

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Section: Animal Model Considerationsmentioning

confidence: 99%

The rational use of animal models in the evaluation of novel bone regenerative therapies

Perić¹,

Dumić-Čule²,

Grčević³

et al. 2015

Bone

130

116

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“…Bone formation predominantly proceeds through two mechanisms: intramembranous (IO) and endochondral ossification (EO). With varying degrees of success, both mechanisms are exploited for bone graft development, using stem cells and other cell types (Bahney et al, 2014;Huang et al, 2006;Olsen et al, 2000;Tortelli et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…As the process continues, the chondrogenic matrix is calcified and degraded, resulting in the release of these molecules (Nagai and Aoki, 2002;Ortega et al, 2004;Street et al, 2002), which trigger cell migration, blood vessel invasion and ultimately bone formation (Boyan et al, 1992;Chen et al, 2012;Gawlitta et al, 2010;Gerber, 1999). It has previously been shown that EO can be mimicked in order to achieve bone formation www.ecmjournal.org using chondrogenically primed mesenchymal stem cell (MSC) pellets (Farrell et al, 2011;van der Stok et al, 2014). Chondrogenically differentiated MSC pellets in vitro for 28 d result in vascularised, endochondral bone when subcutaneously implanted in vivo for 8 weeks.…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stem cell-mediated endochondral ossification utilising micropellets and brief chondrogenic priming

Knuth¹,

Witte-Bouma²,

Ridwan³

et al. 2017

eCM

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With limited autologous and donor bone graft availability, there is an increasing need for alternative graft substitutes. We have previously shown that chondrogenically priming mesenchymal stem cell (MSC) pellets for 28 d in vitro will reproducibly result in endochondral bone formation after in vivo implantation. However, pellet priming time for clinical applications is quite extensive. A micropellet (μpellet)-fibrin construct was developed and coupled, with a shorter priming period, determined by an in vitro time course experiment. In vitro data showed expression of chondrogenic genes and matrix production after 7 d of chondrogenic priming, indicating that briefer priming could possibly be used to induce bone formation in vivo. 7 and 28 d primed pellet, pellet-fibrin and μpellet-fibrin constructs were cultured for in vitro analysis and implanted subcutaneously for 8 weeks into nude mice. μpellet-fibrin constructs, cultured in vitro for 7 or 28 d, produced comparable bone to standard pellets in vivo. MSC-mediated bone formation was achieved following only 7 d of in vitro priming. Bone formation in vivo appeared to be influenced by overall matrix production pre-implantation. Given this short priming time and the injectable nature of the μpellet-fibrin constructs, this approach might be further developed as an injectable bone substitute, leading to a minimally-invasive treatment option, which would allow for tailored filling of bone defects.

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“…induce osteogenesis in different types of cells; including mesenchymal stem cells (MSCs) [1,2,[6][7][8][9] hematopoietic stem cells (HSCs), multipotent adult progenitor cells (MAPCs), and umbilical cord blood (UCBSCs), and embryonic stem cells (ESCs) [10][11][12][13]. Beside bone marrow and blood, the focus of interest in the field of tissue engineering currently lies on other ethically accessible cell reservoirs such as human endometrium.…”

Section: J Ai Et Almentioning

confidence: 99%

BMP-2 can promote the osteogenic differentiation of human endometrial stem cells

Azizi

Shamsian

et al. 2014

Asian Biomedicine

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Background: Human endometrial-derived stem cells (hEnSCs) as multipotent accessible source of cells are known as useful cell candidates in the field of bone tissue engineering. However, the effect of bone morphogenic protein-2 (BMP-2) as an osteoinductive growth factor has not been clearly ascertained. Objective: To evaluate the effect of the remarkable osteoinductive growth factor BMP-2, on promotion of osteogenic differentiation in hEnSCs. Methods: Endometrial biopsies were obtained from healthy women referred to the hospital for infertility treatment. After tissue digestion in collagenase, the isolated endometrial cells were expanded in Dulbecco's modified Eagle medium (DMEM) supplemented with 10% FBS. The propagated cells were characterized based on the expression of endometrial (CD90, CD105), endothelial (CD31), and hematopoietic (CD34, CD133) stem cell markers. Cells were differentiated in osteogenic medium containing DMEM supplemented with 10% FBS, 10 nM dexamethasone, 50 μg/ml Ascorbic acid, and 10 mM β-glycerophosphate in the presence or absence of BMP-2 for 21 days. Alizarin red staining was performed to verify the matrix mineralization. Immunocytochemical staining was conducted to detect the expression of OCT-4, CD133, and osteopontin as well as osteocalcin. The expression of osteoblast transcripts, including osteopontin, osteonectin, and alkaline phosphatase (ALP) were analyzed by semi quantitative PCR. Results:The expanded EnSCs were spindle shaped. They were positive for the expression of Oct-4, CD90, and CD105, while they were negative for endothelial and hematopoietic markers. The matrix mineralization was confirmed by Alizarin red in both groups at day 21. Although the expression of osteopontin and osteocalcin was detected in both groups by immunological staining, the expression of osteocalcin was more intense in the presence of BMP-2. ALP, Osteonectin and osteopontin transcripts were expressed in all groups; however, the expression of ALP and osteopontin was upregulated in the presence of BMP-2. Conclusion: BMP-2 as an osteoinductive growth factor, could promote the osteogenic differentiation of EnSCs in vitro.

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The development of tissue-engineered bone of different origin through endochondral and intramembranous ossification following the implantation of mesenchymal stem cells and osteoblasts in a murine model

Cited by 129 publications

References 30 publications

The rational use of animal models in the evaluation of novel bone regenerative therapies

The rational use of animal models in the evaluation of novel bone regenerative therapies

Mesenchymal stem cell-mediated endochondral ossification utilising micropellets and brief chondrogenic priming

BMP-2 can promote the osteogenic differentiation of human endometrial stem cells

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