Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

Kiernan, Jeffrey; Hu, Sally; Grynpas, Marc D.; Davies, John E.; Stanford, William L.

doi:10.5966/sctm.2015-0231

Cited by 72 publications

(45 citation statements)

References 63 publications

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“…It is particularly urgent to clarify the mechanism of stem cell differentiation and develop new strategies to induce stem cell differentiation. Recent advances have demonstrated that inducing mesenchymal stem cells differentiation into osteoblasts and promoting bone formation might be a new therapeutic approach 34,35 . Currently, hUC‐MSCs have been identified as promising sources of mesenchymal stem cells according to their capacity of self‐renewal, multipotency and low immunogenic properties 36 and better proliferative ability than other mesenchymal stem cells 37‐39 .…”

Section: Discussionmentioning

confidence: 99%

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

et al. 2020

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Objectives: Increasing evidences suggest that inducing mesenchymal stem cells to differentiate into osteoblasts has been as an especially important component in the prevention and therapy for degenerative bone disease. Here, we identify a novel lncRNA, linc02349, which increases significantly during osteogenic differentiation. Materials and methods:Human umbilical cord-derived stem cells (hUC-MSCs) and dental pulp mesenchymal stem cells were used. Overexpression and knockdown of linc02349 in cell lines were generated using lentiviral-mediated gene delivery method.Bioinformatics prediction, Ago2-RIP assay and dual-luciferase reporter system were employed to examine miRNA which interacts with linc02349. The RNA FISH assay was performed to identify the subcelluar location of linc02349. Alizarin Red S staining, ALP staining and qPCR were applied to identify the osteogenic differentiation. The potential linc02349-regulated genes, miR-25-3p and miR-33b-5p, were explored by ChIP, RIP and Western blotting assays. Micro-CT was used to measure the osteogenic content in bone formation assay in vivo. Results: Linc02349 overexpression improves osteogenic differentiation by in vitroand in vivo analysis. Mechanistically, linc02349 acts as a molecular sponge for miR-25-3p and miR-33b-5p to control expression abundance of SMAD5 and Wnt10b,

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Section: Discussionmentioning

confidence: 99%

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

et al. 2020

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“…More than 50% of periosteal cells are Sca‐1+; they showed osteogenic differentiation potential in vitro, and pro‐angiogenic ability in vivo . In addition, mice with global knockout of Sca1+ had an osteoporotic phenotype . Within a healing long‐bone defect, the distribution of these key progenitor populations is still unclear.…”

Section: Introductionmentioning

confidence: 99%

“…(25) In addition, mice with global knockout of Sca1þ had an osteoporotic phenotype. (26) Within a healing long-bone defect, the distribution of these key progenitor populations is still unclear. In addition, their responses to mechanical loading are virtually unknown.…”

Section: Introductionmentioning

confidence: 99%

Mechanical Loading Promotes the Expansion of Primitive Osteoprogenitors and Organizes Matrix and Vascular Morphology in Long Bone Defects

Liu

Cabahug‐Zuckerman

Stubbs

et al. 2019

Journal of Bone and Mineral Research

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Elucidating the effects of mechanical stimulation on bone repair is crucial for optimization of the healing process. Specifically, the regulatory role that mechanical loading exerts on the osteogenic stem cell pool and vascular morphology during healing is incompletely understood. Because dynamic loading has been shown to enhance osteogenesis and repair, we hypothesized that loading induces the expansion of the osteoprogenitor cell population within a healing bone defect, leading to an increased presence of osteogenic cells. We further hypothesized that loading during the repair process regulates vascular and collagen matrix morphology and spatial interactions between vessels and osteogenic cells. To address these hypotheses, we used a mechanobiological bone repair model, which produces a consistent and reproducible intramembranous repair response confined in time and space. Bilateral tibial defects were created in adult C57BL/6 mice, which were subjected to axial compressive dynamic loading either during the early cellular invasion phase on postsurgical days (PSDs) 2 to 5 or during the matrix deposition phase on PSD 5 to 8. Confocal and two‐photon microscopy was used to generate high‐resolution three‐dimensional (3D) renderings of longitudinal thick sections of the defect on PSD 10. Endomucin (EMCN)‐positive vessels, Paired related homeobox 1 (Prrx1+) stem cell antigen‐1 positive (Sca‐1+) primitive osteoprogenitors (OPCs), and osterix positive (Osx+) preosteoblasts were visualized and quantified using deep tissue immunohistochemistry. New bone matrix was visualized with second harmonic generation autofluorescence of collagen fibers. We found that mechanical loading during the matrix deposition phase (PSD 5 to 8) increased vessel volume and number, and aligned vessels and collagen fibers to the load‐bearing direction of bone. Furthermore, loading led to a significant increase in the proliferation and number of Prrx1+ Sca‐1+ primitive OPCs, but not Osx+ preosteoblasts within the defect. Together, these data illustrate the adaptation of both collagen matrix and vascular morphology to better withstand mechanical load during bone repair, and that the mechanoresponsive cell population consists of the primitive osteogenic progenitors. © 2019 American Society for Bone and Mineral Research.

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“…The deteriorating changes of bone in the OVX rats injected with saline was reflected by the thinning of the trabeculae, reduced bone surface area and bone volume in the proximal femur. These micro-structural changes are common problems in osteoporotic patients, causing fragility fractures (15,19). The small sample number of only 6 rats per group means that trends towards increased trabecular thickness in the femora of OVX rats injected with CXCR4 modified cells, were not clinically significant compared to untreated counterparts.…”

Section: Discussionmentioning

confidence: 99%

CXCR4 Has the Potential to Enhance Bone Formation in Osteopenic Rats

Sanghani

Osagie

Samizadeh

et al. 2018

Tissue Engineering Part A

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Systemic Mesenchymal Stromal Cell Transplantation Prevents Functional Bone Loss in a Mouse Model of Age-Related Osteoporosis

Cited by 72 publications

References 63 publications

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

Linc02349 promotes osteogenesis of human umbilical cord‐derived stem cells by acting as a competing endogenous RNA for miR‐25‐3p and miR‐33b‐5p

Mechanical Loading Promotes the Expansion of Primitive Osteoprogenitors and Organizes Matrix and Vascular Morphology in Long Bone Defects

CXCR4 Has the Potential to Enhance Bone Formation in Osteopenic Rats

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