CXCR4 Has the Potential to Enhance Bone Formation in Osteopenic Rats

Sanghani, Anita; Osagie, Liza; Samizadeh, Soureouseh; Coathup, Melanie; Kalia, Priya; Silvio, L. Di; Blunn, Gordon

doi:10.1089/ten.tea.2018.0121

Cited by 9 publications

(5 citation statements)

References 21 publications

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“…119 CXCL12-CXCR4 signalling is also indispensable to maintaining the hematopoietic stem cell (HSC) pool in adult bone marrow, which is closely related to osteogenesis and angiogenesis. 120 Sanghani et al 98 harvested MSCs from young and OVX animals. These cells were transfected with CXCR4 cDNA and administered intravenously in OVX rats.…”

Section: Therapeutic Outcomesmentioning

confidence: 99%

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

et al. 2020

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Osteoporosis is a systemic metabolic bone disease with characteristics of bone loss and microstructural degeneration. The personal and societal costs of osteoporosis are increasing year by year as the ageing of population, posing challenges to public health care. Homing disorders, impaired capability of osteogenic differentiation, senescence of mesenchymal stem cells (MSCs), an imbalanced microenvironment, and disordered immunoregulation play important roles during the pathogenesis of osteoporosis. The MSC transplantation promises to increase osteoblast differentiation and block osteoclast activation, and to rebalance bone formation and resorption. Preclinical investigations on MSC transplantation in the osteoporosis treatment provide evidences of enhancing osteogenic differentiation, increasing bone mineral density, and halting the deterioration of osteoporosis. Meanwhile, the latest techniques, such as gene modification, targeted modification and co‐transplantation, are promising approaches to enhance the therapeutic effect and efficacy of MSCs. In addition, clinical trials of MSC therapy to treat osteoporosis are underway, which will fill the gap of clinical data. Although MSCs tend to be effective to treat osteoporosis, the urgent issues of safety, transplant efficiency and standardization of the manufacturing process have to be settled. Moreover, a comprehensive evaluation of clinical trials, including safety and efficacy, is still needed as an important basis for clinical translation.

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Section: Therapeutic Outcomesmentioning

confidence: 99%

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

et al. 2020

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“…Previous studies [78–81] have shown that the C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) axis modulates BMSC homing and promotes angiogenesis, and the BMP-2/Smads/Runx2/Osterix axis modulates BMSC osteoblastic differentiation. The crosstalk between these two signaling axes is mediated by CXCR4, which modulates the migration [82] and osteogenic differentiation of BMSCs. Some studies have demonstrated that BMSC migration can also occur via the BMP-Smad1/5/8-twist-related protein 1/activating transcription factor 4 (Twist1/Atf4) [83, 84] and CXCR4/stromal-derived factor 1 (SDF-1) [85–87] axes and the Smad pathway [88].…”

Section: Role Of Bmscs In Bone Regenerative Therapymentioning

confidence: 99%

Mechanism of Action of Icariin in Bone Marrow Mesenchymal Stem Cells

Yang

et al. 2019

Stem Cells International

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Osteoporosis, femoral head necrosis, and congenital bone defects are orthopedic disorders characterized by reduced bone generation and insufficient bone mass. Bone regenerative therapy primarily relies on the bone marrow mesenchymal stem cells (BMSCs) and their ability to differentiate osteogenically. Icariin (ICA) is the active ingredient of Herba epimedii, a common herb used in traditional Chinese medicine (TCM) formulations, and can effectively enhance BMSC proliferation and osteogenesis. However, the underlying mechanism of ICA action in BMSCs is not completely clear. In this review, we provide an overview of the studies on the role and mechanism of action of ICA in BMSCs, to provide greater insights into its potential clinical use in bone regeneration.

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“…The use of MSCs in preclinical trials has been well documented. 35 , 36 Although clinically MSCs have been used locally in the healing of nonunions, particularly tibial and calcaneal, and pre-clinical work has investigated their administration systemically, to migrate to sites of bone injury, very few studies have used cells in combination with PTH to enhance fracture healing. Sheyn et al 19 used intravenous MSCs and teripratide to improve vertebral fracture healing, noting that the additive method enhanced bone formation, and promoted the terminal differentiation of cells down the osteoplastic lineage.…”

Section: Discussionmentioning

confidence: 99%

The role of intermittent PTH administration in conjunction with allogenic stem cell treatment to stimulate fracture healing

Osagie

Meeson

Sanghani-Kerai

et al. 2021

Bone & Joint Research

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Aims A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 106 cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667.

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CXCR4 Has the Potential to Enhance Bone Formation in Osteopenic Rats

Abstract: CXCR4 genetically modified cells from young and ovarectomized sources improve some aspects of bone formation in the ovarectomized model of osteoporosis; and thus, may play a role in patient treatment regimens.

Cited by 9 publications

References 21 publications

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis

Mechanism of Action of Icariin in Bone Marrow Mesenchymal Stem Cells

The role of intermittent PTH administration in conjunction with allogenic stem cell treatment to stimulate fracture healing

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