scholarly journals Dual Delivery of rhPDGF-BB and Bone Marrow Mesenchymal Stromal Cells Expressing the BMP2 Gene Enhance Bone Formation in a Critical-Sized Defect Model

2013 ◽  
Vol 19 (21-22) ◽  
pp. 2495-2505 ◽  
Author(s):  
Shin-Young Park ◽  
Kyoung-Hwa Kim ◽  
Seung-Yun Shin ◽  
Ki-Tae Koo ◽  
Yong-Moo Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Defect Model ◽  
Enhance Bone Formation ◽  
Critical Sized Defect

scholarly journals Medium-Intensity Treadmill Exercise Exerts Beneficial Effects on Bone Modeling Through Bone Marrow Mesenchymal Stromal Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Lingli Zhang ◽  
Yu Yuan ◽  
Wei Wu ◽  
Zhongguang Sun ◽  
Le Lei ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Signaling Pathway ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Treadmill Exercise ◽  
Heterotopic Bone ◽  
Smad Signaling ◽  
Medium Intensity ◽  
Smad Signaling Pathway

As a type of multipotential cells, bone marrow mesenchymal stromal cells (BMMSCs) can differentiate into chondrocytes, osteoblasts, and adipocytes under different loading condition or specific microenvironment. Previous studies have shown that BMMSCs and their lineage-differentiated progeny (for example, osteoblasts), and osteocytes are mechanosensitive in bone. The appropriate physical activity and exercise could help attenuate bone loss, effectively stimulate bone formation, increase bone mineral density (BMD), prevent the progression of osteoporosis, and reduce the risk of bone fractures. Bone morphogenetic protein (BMP) is originally discovered as a protein with heterotopic bone-inducing activity in the bone matrix that exerts a critical role in multiple stages of bone metabolism. In the present study, the medium-intensity treadmill exercise enhanced bone formation and increased osteocalcin (OCN) and osteopontin (OPN) mRNA expression as well as activation of the BMP-Smad signaling pathway in vivo. In order to investigate the effect of a BMP-Smad signaling pathway, we injected mice with activated enzyme inhibitors (LDN-193189HCL) and subjected the mice to treadmill exercise intervention. LDN-193189HCL attenuated the BMD and bone mass mediated by medium-intensity exercise and BMP-Smad signaling pathway.

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation

2015 ◽  
Vol 13 ◽  
pp. 254-265 ◽  
Author(s):  
Wanxun Yang ◽  
Sanne K. Both ◽  
Gerjo J.V.M. van Osch ◽  
Yining Wang ◽  
John A. Jansen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Endochondral Bone Formation ◽  
Endochondral Bone

Disregulated Osteogenesis By Mesenchymal Stromal Cells (MSC) After In Vivo Exposure To Multiple Myeloma: Studies In a Novel Humanized Mouse Model For Bone Remodelling In Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1906-1906
Author(s):  
Richard W.J. Groen ◽  
Willy A. Noort ◽  
Jessica Sigmans ◽  
Aniek van Stralen ◽  
Linda Aalders ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Mouse Model ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Humanized Mouse ◽  
Humanized Mouse Model ◽  
Hybrid Scaffolds

Abstract Multiple myeloma (MM), a B-cell neoplasm characterized by a clonal expansion of malignant plasma cells in the bone marrow (BM), is accompanied by osteolytic lesions and/or diffuse osteopenia in up to 90% of the patients. Even after successful treatment, these MM-induced bone lesions do not normalize. We hypothesized that this might be caused by MM-induced irreversible impairment of the osteoblast function in the BM microenvironment. To study this bone remodeling processes in MM we used a recently developed, humanized mouse model of MM that allows engraftment and outgrowth of patient MM (pMM) cells in a humanized BM niche. To this end, ceramic scaffolds are seeded with culture-expanded human mesenchymal stromal cells (MSCs) from human BM, differentiated in vitro to osteoblasts for 1 week, then implanted subcutaneously in immune-deficient RAG2-/-gc-/--mice and after 6-8 weeks a layer of human bone is deposited on the surface of the scaffolds. Following the injection of luciferase-GFP gene marked primary MM cells (pMM), this results in homing and outgrowth of pMM in the scaffolds (Groen et al., Blood 2012). Here we describe a modification of this in vivo model, by co-implanting MSC loaded scaffolds, with pMM cells adhered to the hybrid scaffolds, at one side of the mouse, and with hybrid scaffolds only (without pMM) at the other side of the mouse. At this contra-lateral location bone formation can take place undisturbed (i.e., not affected by the presence of MM) and serves as an internal control for the osteogenic potential of the osteoblasts. Thus this model allows us to study bidirectional interactions between pMM cells and the osteoblast and the resulting inhibition of osteogenesis. Here we report that outgrowth pMM cells indeed resulted in on average 50-75% decrease in bone formation, and, using bioluminescence imaging, we found an inverse correlation between the size of the tumor and the amount of bone formation: with increasing tumor size, the amount of bone formed was less. Human AML growing in the scaffolds (serving as control) does not influence the bone forming process. At the end of the experiment when we analyzed gene expression in the human stromal cells (CD73+ CD90+ CD105+) that we cultured from scaffolds containing pMM tumors, we found a significant reduction in expression of transcripts for alkaline phosphatase (ALP), collagen1A1 (colA1), osteoglycin (OGN), osteomodulin (OMD), and abnormal spindle-like microcephaly associated (ASPM), genes that have been implicated in osteogenesis. These data suggest that pMM cells interfere with the osteogenic differentiation of MSCs in the context of an in vivo biocompatible scaffold engineered to simulate the human BM microenvironment. Taken together, our data show that co-implanting MSCs together with the pMM cells can serve as a model to study the effect of pMM cells on osteogenesis, which provides a tool to unravel the mutual interaction between MM cells and the bone marrow microenvironment. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cell Therapy: Effect of Locally Injected Mesenchymal Stromal Cells Derived from Bone Marrow or Adipose Tissue on Bone Regeneration of Rat Calvarial Defects

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Gileade P. Freitas ◽  
Helena B. Lopes ◽  
Alann T. P. Souza ◽  
Paula G. F. P. Oliveira ◽  
Adriana L. G. Almeida ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Adipose Tissue ◽  
Cell Therapy ◽  
Bone Formation ◽  
Bone Regeneration ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Local Injection ◽  
Expression Of Genes ◽  
Calvarial Defects

Abstract Treatment of large bone defects is a challenging clinical situation that may be benefited from cell therapies based on regenerative medicine. This study was conducted to evaluate the effect of local injection of bone marrow-derived mesenchymal stromal cells (BM-MSCs) or adipose tissue-derived MSCs (AT-MSCs) on the regeneration of rat calvarial defects. BM-MSCs and AT-MSCs were characterized based on their expression of specific surface markers; cell viability was evaluated after injection with a 21-G needle. Defects measuring 5 mm that were created in rat calvaria were injected with BM-MSCs, AT-MSCs, or vehicle-phosphate-buffered saline (Control) 2 weeks post-defect creation. Cells were tracked by bioluminescence, and 4 weeks post-injection, the newly formed bone was evaluated by µCT, histology, nanoindentation, and gene expression of bone markers. BM-MSCs and AT-MSCs exhibited the characteristics of MSCs and maintained their viability after passing through the 21-G needle. Injection of both BM-MSCs and AT-MSCs resulted in increased bone formation compared to that in Control and with similar mechanical properties as those of native bone. The expression of genes associated with bone formation was higher in the newly formed bone induced by BM-MSCs, whereas the expression of genes involved in bone resorption was higher in the AT-MSC group. Cell therapy based on local injection of BM-MSCs or AT-MSCs is effective in delivering cells that induced a significant improvement in bone healing. Despite differences observed in molecular cues between BM-MSCs and AT-MSCs, both cells had the ability to induce bone tissue formation at comparable amounts and properties. These results may drive new cell therapy approaches toward complete bone regeneration.

Expansion of Bone Marrow Mesenchymal Stromal Cells in Perfused 3D Ceramic Scaffolds Enhances In Vivo Bone Formation

2017 ◽  
Vol 12 (12) ◽  
pp. 1700071 ◽  
Author(s):  
Allison I. Hoch ◽  
Ralph Duhr ◽  
Nunzia Di Maggio ◽  
Arne Mehrkens ◽  
Marcel Jakob ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
In Vivo Bone Formation

scholarly journals The Bone Regeneration Using Bone Marrow Stromal Cells with Moderate Concentration Platelet-Rich Plasma in Femoral Segmental Defect of Rats

2017 ◽  
Vol 11 (1) ◽  
pp. 1-11 ◽  
Author(s):  
Junichi Yamakawa ◽  
Junichi Hashimoto ◽  
Mitsuo Takano ◽  
Michiaki Takagi
Keyword(s):  
Bone Marrow ◽  
Cell Proliferation ◽  
Bone Formation ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Platelet Rich Plasma ◽  
Marrow Stromal Cells ◽  
Segmental Defect ◽  
Defect Model

Background: Platelet-rich plasma (PRP) can provide an assortment of growth factors, but how PRP effects bone regeneration is still unknown. The aim of the study was to explore an optimal method of using PRP and bone marrow stromal cells (BMSCs). Methods: An in vitro experiment was first conducted to determine an appropriate quantity of PRP. BMSCs were cultured with PRP of different concentrations to assess cell proliferation and osteogenic differentiation. Following the in vitro study, a rat femoral segmental defect model was used. Five collagen mixtures consisting of different concentrations of PRP and BMSCs were prepared as follows, i) BMSCs and PRP (platelet 20 x 104/µl), ii) BMSCs and PRP (platelet 100 x 104/µl), iii) BMSCs and PRP (platelet 500 x 104/µl), iv) BMSCs, and v) PRP group (platelet 100 x 104/µl), were used to fill defect. New bone formation was evaluated by soft X-ray and histologic analyses were performed at 2, 4, 6 and 8 weeks postoperatively. Results: The cell proliferation increased PRP concentration-dependently. Cellular alkaline phosphatase activity was higher in moderate concentration than high or low concentration group’s in vitro study. In vivo study, the bone fill percentage of newly formed bone in BMSCs and PRP (platelet 100 x 104/µl) was 46.9% at 8 weeks and increased significantly compared with other groups. Conclusion: BMSCs with moderate level of PRP significantly enhanced bone formation in comparison with BMSCs or PRP transplant in a rat femoral defect model.

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