scholarly journals Bone Marrow Stromal Cells in a Mouse Model of Metal Implant Osseointegration

2020 ◽  
Author(s):  
Alexander Vesprey ◽  
Eun Sung Suh ◽  
Didem Göz Aytürk ◽  
Xu Yang ◽  
Miracle Rogers ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Bone Tissue ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Mechanical Stability ◽  
Lineage Tracing ◽  
Implant Surface ◽  
Metal Implants ◽  
Bone Deposition

ABSTRACTMetal implants are commonly used in orthopaedic surgery. The mechanical stability and longevity of implants depend on adequate bone deposition along the implant surface. The cellular and molecular mechanisms underlying peri-implant bone formation (i.e. osseointegration) are incompletely understood. Herein, our goal was to determine the specific bone marrow stromal cell populations that contribute to bone formation around metal implants. To do this, we utilized a mouse tibial implant model that is clinically representative of human joint replacement procedures. Using a lineage-tracing approach with the Acta2.creERT2 and Tmem100.creERT2 transgenic alleles, we found that Pdgfra- and Ly6a/Sca1-expressing stromal cells (PαS cells) multiply and differentiate in the peri-implant environment to give rise to osteocytes in newly formed bone tissue. Single cell RNA-seq analysis indicated that PαS cells are quiescent in uninjured bone tissue; however, they express markers of proliferation and osteogenic differentiation shortly after implantation surgery. Our findings indicate that PαS cells are mobilized to repair bone tissue and facilitate implant osseointegration following surgery. Biologic therapies targeting PαS cells might improve osseointegration in patients undergoing orthopaedic procedures.

Effect of cell therapy with osteoblasts differentiated from bone marrow or adipose tissue stromal cells on bone repair

2019 ◽  
Vol 14 (12) ◽  
pp. 1107-1119 ◽  
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 Tissue ◽  
Stromal Cells ◽  
Bone Repair ◽  
Calvarial Bone ◽  
Adipose Tissue Stromal Cells ◽  
Phosphate Buffered Saline

Aim: The aim of this study was to investigate the effect of local injection of osteoblasts differentiated from bone marrow (BM-OB) or adipose tissue (AT-OB) mesenchymal stromal cells on bone tissue formation. Materials & methods: Defects were created in rat calvaria and injected with BM-OB or AT-OB and phosphate-buffered saline without cells were injected as control. Bone formation was evaluated 4 weeks postinjection. Results: Injection of BM-OB or AT-OB resulted in higher bone formation than that obtained with control. The bone tissue induced by cell injections exhibited similar mechanical properties as those of pristine calvarial bone, and its molecular cues suggested the occurrence of a remodeling process. Conclusion: Results of this study demonstrated that cell therapy with osteoblasts induced significant bone formation that exhibited the same quality as that of pre-existent bone.

scholarly journals Circular RNA AFF4 modulates osteogenic differentiation in BM-MSCs by activating SMAD1/5 pathway through miR-135a-5p/FNDC5/Irisin axis

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Chao Liu ◽  
An-Song Liu ◽  
Da Zhong ◽  
Cheng-Gong Wang ◽  
Mi Yu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Regulatory System ◽  
Circular Rna ◽  
Luciferase Reporter ◽  
Integrin Αv

AbstractBone marrow-derived mesenchymal stem cells (BM-MSCs), the common progenitor cells of adipocytes and osteoblasts, have been recognized as the key mediator during bone formation. Herein, our study aim to investigate molecular mechanisms underlying circular RNA (circRNA) AFF4 (circ_AFF4)-regulated BM-MSCs osteogenesis. BM-MSCs were characterized by FACS, ARS, and ALP staining. Expression patterns of circ_AFF4, miR-135a-5p, FNDC5/Irisin, SMAD1/5, and osteogenesis markers, including ALP, BMP4, RUNX2, Spp1, and Colla1 were detected by qRT-PCR, western blot, or immunofluorescence staining, respectively. Interactions between circ_AFF4 and miR-135a-5p, FNDC5, and miR-135a-5p were analyzed using web tools including TargetScan, miRanda, and miRDB, and further confirmed by luciferase reporter assay and RNA pull-down. Complex formation between Irisin and Integrin αV was verified by Co-immunoprecipitation. To further verify the functional role of circ_AFF4 in vivo during bone formation, we conducted animal experiments harboring circ_AFF4 knockdown, and born samples were evaluated by immunohistochemistry, hematoxylin and eosin, and Masson staining. Circ_AFF4 was upregulated upon osteogenic differentiation induction in BM-MSCs, and miR-135a-5p expression declined as differentiation proceeds. Circ_AFF4 knockdown significantly inhibited osteogenesis potential in BM-MSCs. Circ_AFF4 stimulated FNDC5/Irisin expression through complementary binding to its downstream target molecule miR-135a-5p. Irisin formed an intermolecular complex with Integrin αV and activated the SMAD1/5 pathway during osteogenic differentiation. Our work revealed that circ_AFF4, acting as a sponge of miR-135a-5p, triggers the promotion of FNDC5/Irisin via activating the SMAD1/5 pathway to induce osteogenic differentiation in BM-MSCs. These findings gained a deeper insight into the circRNA-miRNA regulatory system in the bone marrow microenvironment and may improve our understanding of bone formation-related diseases at physiological and pathological levels.

Graft Materials and Bone Marrow Stromal Cells in Bone Tissue Engineering

2011 ◽  
Vol 26 (8) ◽  
pp. 1035-1049 ◽  
Author(s):  
Federico Foschi ◽  
Enrico Conserva ◽  
Paolo Pera ◽  
Barbara Canciani ◽  
Ranieri Cancedda ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Marrow ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Marrow Stromal Cells

scholarly journals New Bone Formation in Tuberculous-Infected Vertebral Body Defect after Administration of Bone Marrow Stromal Cells in Rabbit Model

2016 ◽  
Vol 10 (1) ◽  
pp. 1 ◽  
Author(s):  
Ahmad Jabir Rahyussalim ◽  
Tri Kurniawati ◽  
Nurjati Chairani Siregar ◽  
Agus Syahrurachman ◽  
Ismail Hadisubroto Dilogo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Formation ◽  
Vertebral Body ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Rabbit Model ◽  
Marrow Stromal Cells ◽  
New Bone Formation

Reconstitution of PTEN activity by CK2 inhibitors and interference with the PI3-K/Akt cascade counteract the antiapoptotic effect of human stromal cells in chronic lymphocytic leukemia

Blood ◽  
2010 ◽  
Vol 116 (14) ◽  
pp. 2513-2521 ◽  
Author(s):  
Medhat Shehata ◽  
Susanne Schnabl ◽  
Dita Demirtas ◽  
Martin Hilgarth ◽  
Rainer Hubmann ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Chronic Lymphocytic Leukemia ◽  
Stromal Cells ◽  
Molecular Mechanisms ◽  
Mononuclear Cells ◽  
Lymphocytic Leukemia ◽  
Therapeutic Concept ◽  
Antiapoptotic Effect ◽  
Human Stromal Cells ◽  
Ck2 Inhibitors

Abstract Evidence suggests that tumor microenvironment is critically involved in supporting survival of chronic lymphocytic leukemia (CLL) cells. However, the molecular mechanisms of this effect and the clinical significance are not fully understood. We applied a microenvironment model to explore the interaction between CLL cells and stromal cells and to elucidate the role of phosphatidylinositol 3 kinase (PI3-K)/Akt/phosphatase and tensin homolog detected on chromosome 10 (PTEN) cascade in this process and its in vivo relevance. Primary human stromal cells from bone marrow, lymph nodes, and spleen significantly inhibited spontaneous apoptosis of CLL cells. Pan–PI3-K inhibitors (LY294002, wortmannin, PI-103), isotype-specific inhibitors of p110α, p110β, p110γ, and small interfering RNA against PI3-K and Akt1 counteracted the antiapoptotic effect of the stromal cells. Induction of apoptosis was associated with a decrease in phosphatidylinositol-3,4,5-triphosphate, PI3-K–p85, and dephosphorylation of phosphatidylinositol-dependent kinase-1 (PDK-1), Akt1, and PTEN. Freshly isolated peripheral blood mononuclear cells from patients with CLL (n = 44) showed significantly higher levels of phosphorylated Akt1, PDK-1, PTEN, and CK2 than healthy persons (n = 8). CK2 inhibitors (4,5,6,7-tetrabromo-1H-benzotriazole, apigenin, and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazol) decreased phosphorylation of PTEN and Akt, induced apoptosis in CLL cells, and enhanced the response to fludarabine. In conclusion, bone marrow microenvironment modulates the PI3-K/Akt/PTEN cascade and prevents apoptosis of CLL cells. Combined inhibition of PI3-K/Akt and recovery of PTEN activity may represent a novel therapeutic concept for CLL.

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