Stimulation of calvarial bone healing with human bone marrow stromal cells versus inhibition with adipose-tissue stromal cells on nanostructured β-TCP-collagen

Bothe, Friederike; Lotz, Benedict; Seebach, Elisabeth; Fischer, Jessica; Hesse, Eliane; Diederichs, Solvig; Richter, Wiltrud

doi:10.1016/j.actbio.2018.06.026

Cited by 19 publications

(12 citation statements)

References 77 publications

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“…Only cells from HIV-, HBV-, and HCV-negative donors were used. Human ASC were obtained from liposuction aspirates of a human donor, and isolated, as described before [56]. Articular chondrocytes were isolated from articular cartilage resected from tibia plateaus of a patient undergoing total knee replacement, as described [57].…”

Section: Isolation and Expansion Of Mscmentioning

confidence: 99%

“…Beta-tricalcium phosphate hydrate (β-TCP) constructs [63] were prepared as described before [56]. In brief, β-TCP grains (10 mg, particle size 0.25-1 μm, Sigma-Aldrich Chemie GmbH, Steinheim, Germany) were autoclaved in 30 μl phosphate-buffered saline (PBS), to preserve hydrophilic properties.…”

Section: Preparation Of β-Tcp Constructsmentioning

confidence: 99%

“…Histological evaluation of expanded MSC after differentiation and explanted β-TCP constructs was performed, as described [56]. In brief, β-TCP constructs or MSC pellets were fixed in 4% paraformaldehyde for 24 h. β-TCP constructs were additionally decalcified in ethylenediaminetetraacetic acid (EDTA) for 4-5 days.…”

Section: Histologymentioning

confidence: 99%

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Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells

et al. 2019

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Background: Mesenchymal stromal cells isolated from bone marrow (MSC) represent an attractive source of adult stem cells for regenerative medicine. However, thorough research is required into their clinical application safety issues concerning a risk of potential neoplastic degeneration in a process of MSC propagation in cell culture for therapeutic applications. Expansion protocols could preselect MSC with elevated levels of growth-promoting transcription factors with oncogenic potential, such as c-MYC. We addressed the question whether c-MYC expression affects the growth and differentiation potential of human MSC upon extensive passaging in cell culture and assessed a risk of tumorigenic transformation caused by MSC overexpressing c-MYC in vivo. Methods: MSC were subjected to retroviral transduction to induce expression of c-MYC, or GFP, as a control. Cells were expanded, and effects of c-MYC overexpression on osteogenesis, adipogenesis, and chondrogenesis were monitored. Ectopic bone formation properties were tested in SCID mice. A potential risk of tumorigenesis imposed by MSC with c-MYC overexpression was evaluated. Results: C-MYC levels accumulated during ex vivo passaging, and overexpression enabled the transformed MSC to significantly overgrow competing control cells in culture. C-MYC-MSC acquired enhanced biological functions of c-MYC: its increased DNA-binding activity, elevated expression of the c-MYC-binding partner MAX, and induction of antagonists P19ARF/P16INK4A. Overexpression of c-MYC stimulated MSC proliferation and reduced osteogenic, adipogenic, and chondrogenic differentiation. Surprisingly, c-MYC overexpression also caused an increased COL10A1/COL2A1 expression ratio upon chondrogenesis, suggesting a role in hypertrophic degeneration. However, the in vivo ectopic bone formation ability of c-MYC-transduced MSC remained comparable to control GFP-MSC. There was no indication of tumor growth in any tissue after transplantation of c-MYC-MSC in mice. Conclusions: C-MYC expression promoted high proliferation rates of MSC, attenuated but not abrogated their differentiation capacity, and did not immediately lead to tumor formation in the tested in vivo mouse model. However, upregulation of MYC antagonists P19ARF/P16INK4A promoting apoptosis and senescence, as well as an observed shift towards a hypertrophic collagen phenotype and cartilage degeneration, point to lack of safety for clinical application of MSC that were manipulated to overexpress c-MYC for their better expansion.

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Section: Isolation and Expansion Of Mscmentioning

confidence: 99%

Section: Preparation Of β-Tcp Constructsmentioning

confidence: 99%

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Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells

et al. 2019

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“…As a major contributor to bone formation, mesenchymal stem cells (MSCs) retain self-renewal capability and multi-lineage differentiation capacity into various mesodermal tissues including bone and cartilage, and they have been reported to play a key role in the healing of bone defects. Among the various osteogenic seed cells, bone marrow MSCs (BMSCs) are easy to harvest from abundant sources and exhibit reduced donor morbidity, making them a promising candidate for massive bone repair 4–6 . Moreover, the administration of BMSCs has been applied for the treatment of several diseases, including bone defects, rheumatoid arthritis (RA), and osteoarthritis, with promising results not only in animal models but also in clinical trials as well 7–9 .…”

Section: Introductionmentioning

confidence: 99%

Extracellular IL-37 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the PI3K/AKT signaling pathway

Zhang

Hang

et al. 2019

Cell Death Dis

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Interleukin (IL)-37, a pivotal anti-inflammatory cytokine and a fundamental inhibitor of innate immunity, has recently been shown to be abnormally expressed in several autoimmune-related orthopedic diseases, including rheumatoid arthritis, ankylosing spondylitis, and osteoporosis. However, the role of IL-37 during osteogenic differentiation of mesenchymal stem cells (MSCs) remains largely unknown. In this study, extracellular IL-37 significantly increased osteoblast-specific gene expression, the number of mineral deposits, and alkaline phosphatase activity of MSCs. Moreover, a signaling pathway was activated in the presence of IL-37. The enhanced osteogenic differentiation of MSCs due to supplementation of IL-37 was partially rescued by the presence of a PI3K/AKT signaling inhibitor. Using a rat calvarial bone defect model, IL-37 significantly improved bone healing. Collectively, these findings indicate that extracellular IL-37 enhanced osteogenesis of MSCs, at least in part by activation of the PI3K/AKT signaling pathway.

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“…Nonetheless, the regenerative properties of BAG and β-TCP, as used in BTE, are governed by their chemical makeups and physical properties, which can strongly influence regenerative activators associated with repair and/or regeneration [27,28]. For some of the limitations associated with the applications of BAG and β-TCP in BTE, several other engineering strategies have been designed and applied to unleash their full regenerative capabilities.…”

Section: Introductionmentioning

confidence: 99%

The Regenerative Applicability of Bioactive Glass and Beta-Tricalcium Phosphate in Bone Tissue Engineering: A Transformation Perspective

Lowe

Ottensmeyer

et al. 2019

JFB

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The conventional applicability of biomaterials in the field of bone tissue engineering takes into consideration several key parameters to achieve desired results for prospective translational use. Hence, several engineering strategies have been developed to model in the regenerative parameters of different forms of biomaterials, including bioactive glass and β-tricalcium phosphate. This review examines the different ways these two materials are transformed and assembled with other regenerative factors to improve their application for bone tissue engineering. We discuss the role of the engineering strategy used and the regenerative responses and mechanisms associated with them.

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Stimulation of calvarial bone healing with human bone marrow stromal cells versus inhibition with adipose-tissue stromal cells on nanostructured β-TCP-collagen

Cited by 19 publications

References 77 publications

Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells

Impact of c-MYC expression on proliferation, differentiation, and risk of neoplastic transformation of human mesenchymal stromal cells

Extracellular IL-37 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via activation of the PI3K/AKT signaling pathway

The Regenerative Applicability of Bioactive Glass and Beta-Tricalcium Phosphate in Bone Tissue Engineering: A Transformation Perspective

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