Local administration of allogeneic or autologous bone marrow-derived mesenchymal stromal cells enhances bone formation similarly in distraction osteogenesis

Pan, Qi; Li, Ye; Li, Yucong; Wang, Shuangfeng; Kong, Lingchi; Yang, Zhengmeng; Zhang, Xiaoting; Bai, Shanshan; Zong, Zhixian; Chen, Guanghua; Lin, Sien; Li, Gang

doi:10.1016/j.jcyt.2020.12.005

Cited by 11 publications

(7 citation statements)

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“…This animal model usually quickly exhibited OA phenotype around 4 weeks post-surgery, and we expected to evaluate the relative long-term therapeutic outcome (8 weeks after surgery), which may better mimic the clinical settings for the treatments of OA patients. And recent studies from our group have demonstrated allogeneic MSCs transplantation possessed similar therapeutic e cacy as autologous MSCs on bone formation of distraction osteogenesis rat model, indicating lower immune response associated to allogeneic MSCs therapy [35].…”

Section: Discussionmentioning

confidence: 81%

Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

Lin¹,

Yang²,

Liu³

et al. 2021

Preprint

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Background: Osteoarthritis (OA) is a chronic joint disease, characterized by articular cartilage degradation, subchondral bone hardening, and inflammation of the whole synovial joint. There is no pharmacological treatment in slowing down OA progression, leading to costly surgical interventions eventually. Cell therapy using chondrocytes or progenitor cells from different sources has been reported in clinical trials for OA management with some success, but outcomes are varied. Peripheral blood derived mesenchymal stem cells (PB-MSCs) are promising cells owing to their easy collection, superior migration, and differentiation potentials. In the current study, we evaluated the effect of intra-articular administration of PB-MSCs on the progression of OA in mice.Methods: C57BL/6J mice (8-10 weeks old male) were subjected to destabilization of the medial meniscus surgeries (DMM) on their right joints following protocols as previously reported. The mice after DMM were randomly treated with saline (vehicle control), PB-MSCs, or adipose tissue derived MSCs (AD-MSCs) (n = 7 per group). The mice treated with sham surgery were regarded as sham controls (n = 7). PB-MSCs and AD-MSCs were harvested and cultured according to previous published protocols, and pre-labeled with BrdU for 48 h before use. PB-MSCs or AD-MSCs (5 × 105 cells/mouse; passage 3~5) were injected into the right knee joints thrice post-surgery (except sham surgery group). The mice were euthanized at 8 weeks post-surgery and knee joint samples were collected for micro-CT and histological examinations.Results: PB-MSCs administration significantly reduced hardening of subchondral bone comparing to vehicle controls. Safranin O staining showed that PB-MSCs treatment ameliorated degeneration of articular cartilage, which is comparable to AD-MSCs treatment. The expression of catabolic marker MMP13 was significantly reduced in articular cartilage of PB-MSCs-treated groups comparing to vehicle controls. Co-expression of BrdU and Sox9 were detected, indicating injected PB-MSCs differentiated towards chondrocytes in situ. Reduced level of IL-6 in the peripheral sera of PB-MSCs- and AD-MSCs-treated mice was also determined. Conclusions: Repetitive administration of PB-MSCs or AD-MSCs halted OA progression through inhibiting cartilage degradation and inflammation. PB-MSCs may become a promising cell source for cartilage tissue repair and alleviation of OA progression.

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Section: Discussionmentioning

confidence: 81%

Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

Lin¹,

Yang²,

Liu³

et al. 2021

Preprint

Self Cite

View full text Add to dashboard Cite

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“…The microstructure of distal femoral metaphysis was analysed using high-resolution vivaCT 40 (Scanco Medical, Bruttisellen, Switzerland), as previously reported [ 32 , 33 ]. Image acquisition was performed at 70 kV and 114 μA, with a resolution of 17.5 μm per voxel, and the segmentation parameters for the bone from the background were fixed at Sigma = 0.8, Support = 2, and Threshold = 158–1000 [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Bioactive Scaffold Fabricated by 3D Printing for Enhancing Osteoporotic Bone Regeneration

et al. 2022

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We develop a poly (lactic-co-glycolic acid)/β-calcium phosphate (PLGA/TCP)-based scaffold through a three-dimensional (3D) printing technique incorporating icaritin (ICT), a unique phytomolecule, and secretome derived from human fetal mesenchymal stem cells (HFS), to provide mechanical support and biological cues for stimulating bone defect healing. With the sustained release of ICT and HFS from the composite scaffold, the cell-free scaffold efficiently facilitates the migration of MSCs and promotes bone regeneration at the femoral defect site in the ovariectomy (OVX)-induced osteoporotic rat model. Furthermore, mechanism study results indicate that the combination of ICT and HFS additively activates the Integrin–FAK (focal adhesion kinase)–ERK1/2 (extracellular signal-regulated kinase 1/2)–Runx2 (Runt-related transcription factor 2) axis, which could be linked to the beneficial recruitment of MSCs to the implant and subsequent osteogenesis enhancement. Collectively, the PLGA/TCP/ICT/HFS (P/T/I/S) bioactive scaffold is a promising biomaterial for repairing osteoporotic bone defects, which may have immense implications for their translation to clinical practice.

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“…Successful MSC homing can benefit bone formation, and emerging studies have revealed the therapeutic effect of MSC homing in skeleton-related diseases: BMSCs from osteoporotic patients or from aged and OVX mice revealed reduced migration and invasion ability, while administration of allogeneic or autologous bone marrow-derived MSCs improved bone formation in mice subjected to tibia transverse osteotomy. 313 , 314 Nevertheless, the homing ability of endogenous or transplanted MSCs to the bone marrow niche is generally faint. 315 To enhance homing, efforts have been made to target the specific molecular interactions mediating the process.…”

Section: Bone Matrixmentioning

confidence: 99%

Targeting strategies for bone diseases: signaling pathways and clinical studies

Wang

Liu

et al. 2023

Sig Transduct Target Ther

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Since the proposal of Paul Ehrlich’s magic bullet concept over 100 years ago, tremendous advances have occurred in targeted therapy. From the initial selective antibody, antitoxin to targeted drug delivery that emerged in the past decades, more precise therapeutic efficacy is realized in specific pathological sites of clinical diseases. As a highly pyknotic mineralized tissue with lessened blood flow, bone is characterized by a complex remodeling and homeostatic regulation mechanism, which makes drug therapy for skeletal diseases more challenging than other tissues. Bone-targeted therapy has been considered a promising therapeutic approach for handling such drawbacks. With the deepening understanding of bone biology, improvements in some established bone-targeted drugs and novel therapeutic targets for drugs and deliveries have emerged on the horizon. In this review, we provide a panoramic summary of recent advances in therapeutic strategies based on bone targeting. We highlight targeting strategies based on bone structure and remodeling biology. For bone-targeted therapeutic agents, in addition to improvements of the classic denosumab, romosozumab, and PTH1R ligands, potential regulation of the remodeling process targeting other key membrane expressions, cellular crosstalk, and gene expression, of all bone cells has been exploited. For bone-targeted drug delivery, different delivery strategies targeting bone matrix, bone marrow, and specific bone cells are summarized with a comparison between different targeting ligands. Ultimately, this review will summarize recent advances in the clinical translation of bone-targeted therapies and provide a perspective on the challenges for the application of bone-targeted therapy in the clinic and future trends in this area.

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Local administration of allogeneic or autologous bone marrow-derived mesenchymal stromal cells enhances bone formation similarly in distraction osteogenesis

Cited by 11 publications

References 50 publications

Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

Attenuation of Trauma-induced Osteoarthritis by Repetitive Intra-articular Administration of Peripheral Blood Derived Mesenchymal Stem Cells

Bioactive Scaffold Fabricated by 3D Printing for Enhancing Osteoporotic Bone Regeneration

Targeting strategies for bone diseases: signaling pathways and clinical studies

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