Promotion of bone repair by implantation of cryopreserved bone marrow–derived mononuclear cells in a rabbit model of steroid‐associated osteonecrosis

Xie, Xinhui; Wang, Xinluan; He, Yang; Liu, Zhong; Sheng, Hui; Zhang, Ge; Qin, Ling

doi:10.1002/art.34525

Cited by 41 publications

(44 citation statements)

References 48 publications

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“…The structure of the trabecular bone in the volume of interest of the femoral head was evaluated with eXplore software [26,35]. The mean volumetric bone mineral density (BMD) (mg/cc) and trabecular architectural parameters, including the bone tissue volume density (bone volume/total volume, %), trabecular number (expressed as 1/mm), trabecular thickness (expressed as lm), and trabecular spacing (expressed as lm) to define the degree of plate-like and rodlike trabecular bone in the femoral head were measured.…”

Section: Micro-ct Analysismentioning

confidence: 99%

“…The single-labeled surface, double-labeled surface, and interlabeled thickness were measured except in the necrotic areas. The data were used for the following calculations: mineralizing surface/bone surface = (1/2 single-labeled surface + double-labeled surface)/bone surface (expressed as a percent); and, mineral apposition rate = interlabeled thickness per 10 days (expressed as lm/day) [6,35].…”

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

“…The following parameters were assessed: (1) 200 osteocyte lacunae were counted in each established field at 9 200 magnification and then the percentage of the empty osteocyte lacunae was determined [33]; (2) the average diameter of the fat cells was measured in each field and the average diameter for fat cells of each animal was determined [26,33]; (3) the number and diameter of blood vessels were measured and averaged for each sample based on the a-SMA staining slides [3]. The number of blood vessels was expressed per area of tissue (/mm 2 ); (4) the mineralizing surface and bone surface and mineral apposition rate (lm/day) were calculated as described in previous studies [6,35]. The decalcified slices were examined using a light microscope (Olympus BX51, Tokyo, Japan) and the undecalcified slices were observed under a fluorescence microscope (Olympus IX71).…”

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

“…The number of blood vessels in the LIPUS group (7.8 ± 3.6/mm 2 ; 95% CI, 5.5-10.1 mm 2 ) was greater (p = 0.025) than the number in Introduction Approximately 20,000 patients per year are diagnosed with femoral head osteonecrosis in the United States [23]. Steroids, commonly prescribed to patients with systemic lupus erythematosus, nephrotic syndrome, or organ transplantation, are a leading cause of femoral head osteonecrosis; this is known as steroid-associated osteonecrosis [1,35,41]. Once osteonecrosis begins, 80% of femoral heads will collapse if no treatment is administered [32].…”

Section: Introductionmentioning

confidence: 99%

“…It is thought that steroids interrupt blood flow by damaging the endothelial cells and altering lipid metabolism, leading to the production of fat emboli [4,17,18,22]. Studies have shown that bone repair during the early stages of steroid-associated osteonecrosis is inadequate owing to the decreased activity of osteoblasts and bone marrow-derived stem cells after lengthy periods of steroid treatment [5,35].…”

Section: Introductionmentioning

confidence: 99%

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Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Background Steroids are a leading cause of femoral head osteonecrosis. Currently there are no medications available to prevent and/or treat steroid-associated osteonecrosis. Low-intensity pulsed ultrasound (LIPUS) was approved by the FDA for treating delayed union of bone fractures. Some studies have reported that LIPUS can enhance bone formation and local blood flow in an animal model of fracture healing. However, whether the effect of osteogenesis and neovascularization by LIPUS can enhance the repair progress in steroid-associated osteonecrosis is unknown.Questions/purposes We hypothesized that LIPUS may facilitate osteogenesis and neovascularization in the reparative processes of steroid-associated osteonecrosis. Using a rabbit animal model, we asked whether LIPUS affects (1) bone strength and trabecular architecture; (2) blood vessel number and diameter; and (3) BMP-2 and VEGF expression. Methods Bilateral femoral head necrosis was induced by lipopolysaccharide and methylprednisolone in 24 rabbits. The left femoral heads of rabbits received LIPUS therapy (200 mW/cm 2 ) for 20 minutes daily and were classified as the LIPUS group. The right femoral heads of the same rabbits did not receive therapy and were classified as the control group. All rabbits were euthanized 12 weeks after LIPUS therapy. Micro-CT, biomechanical testing, histologic evaluation, immunohistochemistry, quantitative realtime PCR, and Western blot were used for examination of the effects of LIPUS. Results Twelve weeks after LIPUS treatment, the loading strength in the control group was 355 ± 38 N (95% CI, 315-394 N), which was lower (p = 0.028) than that in the LIPUS group (441 ± 78 N; 95% CI, 359-524 N). The bone tissue volume density (bone volume/total volume) in the LIPUS group (49.29% ± 12.37%; 95 % CI, 36.31%-62.27%) was higher (p = 0.022) than that in the control group (37.93% ± 8.37%; 95 % CI, 29.15%-46.72%). The percentage of empty osteocyte lacunae in the LIPUS group (17% ± 4%; 95% CI, 15%-20%) was lower (p = 0.002) than that in the control group (26% ± 9%; 95% CI, 21%-32%). The mineral apposition rate (lm/day) in the LIPUS group (2.3 ± 0.8 lm/day; 95% CI, 1.8 2.8 lm/day) was higher (p = 0.001) than that in the control group (1.6 ± 0.3 lm/day; 95% CL, 1.4-1.8 lm/day). The number of blood vessels in the LIPUS group (7.8 ± 3.6/mm 2 ; 95% CI, 5.5-10.1 mm 2 ) was greater (p = 0.025) than the number in Hanxiao Zhu and Xunzi Cai contributed equally to this work and should be considered as co-first authors.The institution of the authors has received funding from the National Natural Science Foundation of China (Hangzhou, Zhejiang, China) (81101377, 81101345, 81171687, 81371954, 81201414, 81201416, 81401785, 81472113) 123Clin Orthop Relat Res (2015) 473:1830-1839 DOI 10.1007 Clinical Orthopaedics and Related Research ® A Publication of The Association of Bone and Joint Surgeons® the control group (5.7 ± 2.6/mm 2 ; 95% CI, 4.0-7.3 mm 2 ). Messenger RNA (mRNA) and protein expression of BMP-2 in the LIPUS group (75 ± 7, 95% CI, 70-7...

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Section: Micro-ct Analysismentioning

confidence: 99%

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

Section: Histologic Evaluation and Immunohistochemistrymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Zhu

Cai

Lin

et al. 2015

Clinical Orthopaedics &Amp; Related Research

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Important Considerations in the Therapeutic Application of Stem Cells in Bone Healing and Regeneration

Elkhenany

Bourdo

Biris

et al. 2016

Stem Cells in Toxicology and Medicine

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Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

et al. 2017

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Stem cell-based therapy is considered to be a new hope in transplantation medicine. Among stem cells, mesenchymal stem cells (MSCs) are, due to their differentiation and immuno-modulatory characteristics, the most commonly used as therapeutic agents in the treatment of immune-mediated diseases. MSCs migrate to the site of inflammation and modulate immune response. The capacity of MSC to alter phenotype and function of immune cells are largely due to the production of soluble factors which expression varies depending on the pathologic condition to which MSCs are exposed. Under inflammatory conditions, MSCs-derived factors suppress both innate and adaptive immunity by attenuating maturation and capacity for antigen presentation of dendritic cells, by inducing polarization of macrophages towards alternative phenotype, by inhibiting activation and proliferation of T and B lymphocytes and by reducing cytotoxicity of NK and NKT cells. In this review, we emphasized current findings regarding immuno-modulatory effects of MSC-derived factors and emphasize their potential in the therapy of immune-mediated diseases. © 2017 BioFactors, 43(5):633-644, 2017.

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Promotion of bone repair by implantation of cryopreserved bone marrow–derived mononuclear cells in a rabbit model of steroid‐associated osteonecrosis

Cited by 41 publications

References 48 publications

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Low-intensity Pulsed Ultrasound Enhances Bone Repair in a Rabbit Model of Steroid-associated Osteonecrosis

Important Considerations in the Therapeutic Application of Stem Cells in Bone Healing and Regeneration

Mesenchymal stem cell‐derived factors: Immuno‐modulatory effects and therapeutic potential

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