New Insights into Osteogenic and Chondrogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells and Their Potential Clinical Applications for Bone Regeneration in Pediatric Orthopaedics

Giuliani, Nicola; Lisignoli, Gina; Magnani, Marina; Racano, Costantina; Bolzoni, Marina; Palma, Benedetta Dalla; Spolzino, Angelica; Manferdini, Cristina; Abati, Caterina Novella; Toscani, Denise; Facchini, Andrea; Aversa, Franco

doi:10.1155/2013/312501

Cited by 77 publications

(58 citation statements)

References 115 publications

(187 reference statements)

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“…The relative TRAP activity is the more important value in this case [30], as osteoclasts are found only adjacent to new bone and there was less new bone in the LPS-treated mice. ALP is a recognized marker for osteoblasts and other cell types in the bone microenvironment including hypertrophic chondrocytes, MSCs, and vascular pericytes [17,20]. The reduction in ALP at 1 and 2 weeks postoperative in LPS-treated mice was most likely responsible for the reduction in bone volume observed by microCT analysis.…”

Section: Discussionmentioning

confidence: 99%

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation

Behrends

Hui

Gao

et al. 2017

Clinical Orthopaedics &Amp; Related Research

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Background Bone repair is initiated with a local inflammatory response to injury. The presence of systemic inflammation impairs bone healing and often leads to malunion, although the underlying mechanisms remain poorly defined. Our research objective was to use a mouse model of cortical bone repair to determine the effect of systemic inflammation on cells in the bone healing microenvironment. Question/Purposes (1) Does systemic inflammation, induced by lipopolysaccharide (LPS) administration affect the quantity and quality of regenerating bone in primary bone healing? (2) Does systemic inflammation alter vascularization and the number or activity of inflammatory cells, osteoblasts, and osteoclasts in the bone healing microenvironment? Methods Cortical defects were drilled in the femoral diaphysis of female and male C57BL/6 mice aged 5 to 9 months that were treated with daily systemic injections of LPS or physiologic saline as control for 7 days. Mice were euthanized at 1 week (Control, n = 7; LPS, n = 8), 2 weeks (Control, n = 7; LPS, n = 8), and 6 weeks (Control, n = 9; LPS, n = 8) after surgery. The quantity (bone volume per tissue volume [BV/TV]) and microarchitecture (trabecular separation and thickness, porosity) of bone in the defect were quantified with time using microCT. The presence or activity of vascular endothelial cells (CD34), macrophages (F4/80), osteoblasts (alkaline phosphatase [ALP]), and osteoclasts (tartrate-resistant acid phosphatase [TRAP]) were evaluated using histochemical analyses.The institution of one or more of the authors (JEH, PAM) has received, during the study period, funding from the Fonds de recherche Santé Québec. The remaining authors certify that neither he or she, nor a member of his or her immediate family, has funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. Results Only one of eight defects was bridged completely 6 weeks after surgery in LPS-injected mouse bones compared with seven of nine defects in the control mouse bones (odds ratio [OR], 0.04; 95% CI, 0.003-0.560; p = 0.007). The decrease in cortical bone in LPS-treated mice was reflected in reduced BV/TV (21% ± 4% vs 39% ± 10%; p\0.01), increased trabecular separation (240 ± 36 lm vs 171 ± 29 lm; p \ 0.01), decreased trabecular thickness (81 ± 18 lm vs 110 ± 22 lm; p = 0.02), and porosity (79% ± 4% vs 60% ± 10%; p \ 0.01) at 6 weeks postoperative. Defective healing was accompanied by decreased CD34 (1.1 ± 0.6 vs 3.4 ± 0.9; p\0.01), ALP (1.9 ± 0.9 vs 6.1 ± 3.2; p = 0.03), and TRAP (3.3 ± 4.7 vs 7.2 ± 4.0; p = 0.01) activity, and increased F4/80 (13 ± 2.6 vs 6.8 ± 1.7; p \ 0.01) activity at 2 weeks postoperative. Conclusion The results indicate that LPS-induced systemic inflammation reduced the amount and impaired the quality of bone regenerated in mouse femurs. The effects were associated with impaired revascularization, decreased bone turnover by osteoblasts...

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Section: Discussionmentioning

confidence: 99%

Defective Bone Repair in C57Bl6 Mice With Acute Systemic Inflammation

Behrends

Hui

Gao

et al. 2017

Clinical Orthopaedics &Amp; Related Research

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“…Stem cell therapy, as one of the methods used in the bone repair process, has been developed over the last 2 decades [Giuliani et al, 2013]. The involvement of mesenchymal stem cells (MSCs) in the bone healing process is critical, in particular for difficult nonunion fractures resulting from trauma, blood insufficiency, and other conditions [Grayson et al, 2015;Melek, 2015].…”

mentioning

confidence: 99%

Role of Mesenchymal Stem Cells in Bone Regenerative Medicine: What Is the Evidence?

Oryan

Kamali²,

Moshiri³

et al. 2017

Cells Tissues Organs

272

191

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Healing and regeneration of bone injuries, particularly those that are associated with large bone defects, are a complicated process. There is growing interest in the application of osteoinductive and osteogenic growth factors and mesenchymal stem cells (MSCs) in order to significantly improve bone repair and regeneration. MSCs are multipotent stromal stem cells that can be harvested from many different sources and differentiated into a variety of cell types, such as preosteogenic chondroblasts and osteoblasts. The effectiveness of MSC therapy is dependent on several factors, including the differentiating state of the MSCs at the time of application, the method of their delivery, the concentration of MSCs per injection, the vehicle used, and the nature and extent of injury, for example. Tissue engineering and regenerative medicine, together with genetic engineering and gene therapy, are advanced options that may have the potential to improve the outcome of cell therapy. Although several in vitro and in vivo investigations have suggested the potential roles of MSCs in bone repair and regeneration, the mechanism of MSC therapy in bone repair has not been fully elucidated, the efficacy of MSC therapy has not been strongly proven in clinical trials, and several controversies exist, making it difficult to draw conclusions from the results. In this review, we update the recent advances in the mechanisms of MSC action and the delivery approaches in bone regenerative medicine. We will also review the most recent clinical trials to find out how MSCs may be beneficial for treating bone defects.

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“…BMP1 is involved in ECM organisation by cleaving propeptides of procollagen and promoting fibril formation [25] and is a are multifunctional proteins that are required transcription factors involved in OB lineage determination, bone formation, and remodelling [27,28], and in the regulation of the expression of several genes (e.g., bone matrix genes, OC, COL1A1 [29]). SOX9 is the primary transcription factor of chondrogenesis [30].…”

Section: Discussionmentioning

confidence: 99%