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  • 1
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    Online Resource
    Preoperative uncorrectable tibiofemoral subluxation can worsen clinical outcomes after fixed-bearing unicompartmental knee arthroplasty: a retrospective analysis
    Springer Science and Business Media LLC ; 2021
    In:  Archives of Orthopaedic and Trauma Surgery Vol. 142, No. 10 ( 2021-09-08), p. 2865-2874
    Details
    In: Archives of Orthopaedic and Trauma Surgery, Springer Science and Business Media LLC, Vol. 142, No. 10 ( 2021-09-08), p. 2865-2874
    Type of Medium: Online Resource
    ISSN: 1434-3916
    URL: Article
    DOI: 10.1007/s00402-021-04157-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1458452-9
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  • 2
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    Ageing attenuates bone healing by mesenchymal stem cells in a microribbon hydrogel with a murine long bone critical-size defect model
    Springer Science and Business Media LLC ; 2022
    In:  Immunity & Ageing Vol. 19, No. 1 ( 2022-12)
    Details
    In: Immunity & Ageing, Springer Science and Business Media LLC, Vol. 19, No. 1 ( 2022-12)
    Abstract: Despite the high incidence of fractures and pseudoarthrosis in the aged population, a potential role for the use of mesenchymal stem cells (MSCs) in the treatment of bone defects in elderly patients has not been elucidated. Inflammation and the innate immune system, including macrophages, play crucial roles in the differentiation and activation of MSCs. We have developed lentivirus-transduced interleukin 4 (IL4) over-expressing MSCs (IL4-MSCs) to polarize macrophages to an M2 phenotype to promote bone healing in an established young murine critical size bone defect model. In the current study, we explore the potential of IL4-MSCs in aged mice. Methods A 2 mm femoral diaphyseal bone defect was created and fixed with an external fixation device in 15- to 17-month-old male and female BALB/c mice. Microribbon (µRB) scaffolds (Sc) with or without encapsulation of MSCs were implanted in the defect sites. Accordingly, the mice were divided into three treatment groups: Sc-only, Sc + MSCs, and Sc + IL4-MSCs. Mice were euthanized six weeks after the surgery; subsequently, MicroCT (µCT), histochemical and immunohistochemical analyses were performed. Results µCT analysis revealed that bone formation was markedly enhanced in the IL4-MSC group. Compared with the Sc-only, the amount of new bone increased in the Sc + MSCs and Sc + IL4-MSC groups. However, no bridging of bone was observed in all groups. H & E staining showed fibrous tissue within the defect in all groups. Alkaline phosphatase (ALP) staining was increased in the Sc + IL4-MSC group. The Sc + IL4-MSCs group showed a decrease in the number of M1 macrophages and an increase in the number of M2 macrophages, with a significant increase in the M2/M1 ratio. Discussion IL4 promotes macrophage polarization to an M2 phenotype, facilitating osteogenesis and vasculogenesis. The addition of IL4-MSCs in the µRB scaffold polarized macrophages to an M2 phenotype and increased bone formation; however, complete bone bridging was not observed in any specimens. These results suggest that IL4-MSCs are insufficient to heal a critical size bone defect in aged mice, as opposed to younger animals. Additional therapeutic strategies are needed in this challenging clinical scenario.
    Type of Medium: Online Resource
    ISSN: 1742-4933
    URL: Article
    DOI: 10.1186/s12979-022-00272-1
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2168941-6
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  • 3
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    Metabolic profile of mesenchymal stromal cells and macrophages in the presence of polyethylene particles in a 3D model
    Springer Science and Business Media LLC ; 2023
    In:  Stem Cell Research & Therapy Vol. 14, No. 1 ( 2023-04-21)
    Details
    In: Stem Cell Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-04-21)
    Abstract: Continuous cross talk between MSCs and macrophages is integral to acute and chronic inflammation resulting from contaminated polyethylene particles (cPE); however, the effect of this inflammatory microenvironment on mitochondrial metabolism has not been fully elucidated. We hypothesized that (a) exposure to cPE leads to impaired mitochondrial metabolism and glycolytic reprogramming and (b) macrophages play a key role in this pathway. Methods We cultured MSCs with/without uncommitted M0 macrophages, with/without cPE in 3-dimensional gelatin methacrylate (3D GelMA) constructs/scaffolds. We evaluated mitochondrial function (membrane potential and reactive oxygen species—ROS production), metabolic pathways for adenosine triphosphate (ATP) production (glycolysis or oxidative phosphorylation) and response to stress mechanisms. We also studied macrophage polarization toward the pro-inflammatory M1 or the anti-inflammatory M2 phenotype and the osteogenic differentiation of MSCs. Results Exposure to cPE impaired mitochondrial metabolism of MSCs; addition of M0 macrophages restored healthy mitochondrial function. Macrophages exposed to cPE-induced glycolytic reprogramming, but also initiated a response to this stress to restore mitochondrial biogenesis and homeostatic oxidative phosphorylation. Uncommitted M0 macrophages in coculture with MSC polarized to both M1 and M2 phenotypes. Osteogenesis was comparable among groups after 21 days. Conclusion This work confirmed that cPE exposure triggers impaired mitochondrial metabolism and glycolytic reprogramming in a 3D coculture model of MSCs and macrophages and demonstrated that macrophages cocultured with MSCs undergo metabolic changes to maintain energy production and restore homeostatic metabolism.
    Type of Medium: Online Resource
    ISSN: 1757-6512
    URL: Article
    DOI: 10.1186/s13287-023-03260-4
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2548671-8
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  • 4
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    Sex differences in the therapeutic effect of unaltered versus NFκB sensing IL-4 over-expressing mesenchymal stromal cells in a murine model of chronic inflammatory bone loss
    Frontiers Media SA ; 2022
    In:  Frontiers in Bioengineering and Biotechnology Vol. 10 ( 2022-8-15)
    Details
    In: Frontiers in Bioengineering and Biotechnology, Frontiers Media SA, Vol. 10 ( 2022-8-15)
    Abstract: Wear particles from joint arthroplasties induce chronic inflammation associated with prolonged upregulation of nuclear factor kappa-B (NF-κB) signaling in macrophages and osteoclasts, which leads to osteolysis and implant loosening. Mesenchymal stromal cell (MSC)-based therapy showed great potential for immunomodulation and mitigation of osteolysis in vivo , especially in the chronic phase of inflammation. We previously generated genetically modified MSCs that secrete the anti-inflammatory cytokine interleukin 4 (IL-4) in response to NF-κB activation (NFκB-IL-4 MSCs). However, whether the impact of sexual difference in the internal environment can alter the therapeutic effects of IL-4 over-secreting MSCs that simultaneously mitigate prolonged inflammation and enhance bone formation remains unknown. This study investigated the therapeutic effects of unaltered MSCs versus NFκB-IL-4 MSCs in mitigating chronic inflammation and enhancing bone formation in male and female mice. The murine model was established by continuous infusion of polyethylene particles contaminated with lipopolysaccharide (cPE) into the medullary cavity of the distal femur for 6 weeks to induce chronic inflammation. Unaltered MSCs or NFκB-IL-4 MSCs were infused into the femoral intramedullary cavity in sex-matched groups beginning 3 weeks after primary surgery. Femurs were harvested at 6 weeks, and bone marrow density was measured with micro-computational tomography. Numbers of osteoclast-like cells, osteoblasts, and macrophages were evaluated with histochemical and immunofluorescence staining. cPE infusion resulted in severe bone loss at the surgery site, increased tartrate-resistant acid phosphatase positive osteoclasts and M1 pro-inflammatory macrophages, and decreased alkaline phosphatase expression. MSC-based therapy effectively decreased local bone loss and polarized M1 macrophages into an M2 anti-inflammatory phenotype. In females, unaltered MSCs demonstrated a larger impact in enhancing the osteogenesis, but they demonstrated similar anti-inflammatory effects compared to NFκB-IL-4 MSCs. These results demonstrated that local inflammatory bone loss can be effectively modulated via MSC-based treatments in a sexually dimorphic manner, which could be an efficacious therapeutic strategy for treatment of periprosthetic osteolysis in both genders.
    Type of Medium: Online Resource
    ISSN: 2296-4185
    URL: Article
    DOI: 10.3389/fbioe.2022.962114
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2719493-0
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  • 5
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    DataSheet1.PDF
    Frontiers Media SA ; 2023
    In:  Frontiers in Cell and Developmental Biology Vol. 11 ( 2023-6-30)
    Details
    In: Frontiers in Cell and Developmental Biology, Frontiers Media SA, Vol. 11 ( 2023-6-30)
    Abstract: Novel minimally invasive strategies are needed to obtain robust bone healing in complex fractures and bone defects in the elderly population. Local cell therapy is one potential option for future treatment. Mesenchymal stromal cells (MSCs) are not only involved in osteogenesis but also help direct the recruitment of macrophages during bone regeneration via MSC-macrophage crosstalk. The C-C motif chemokine ligand 2 (CCL2) is an inflammatory chemokine that is associated with the migration of macrophages and MSCs during inflammation. This study investigated the use of CCL2 as a therapeutic target for local cell therapy. MSCs and macrophages were isolated from 10 to 12 week-old BALB/c male mice. Genetically modified CCL2 over-expressing MSCs were produced using murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector. Osteogenic differentiation assays were performed using MSCs with or without macrophages in co-culture. Cell migration assays were also performed. MSCs transfected with murine CCL2-secreting pCDH-CMV-mCCL2-copGFP expressing lentivirus vector showed higher levels of CCL2 secretion compared to unaltered MSCs ( p & lt; 0.05). Genetic manipulation did not affect cell proliferation. CCL2 did not affect the osteogenic ability of MSCs alone. However, acute (1 day) but not sustained (7 days) stimulation with CCL2 increased the alizarin red-positive area when MSCs were co-cultured with macrophages ( p & lt; 0.001). Both recombinant CCL2 ( p & lt; 0.05) and CCL2 released from MSCs ( p & lt; 0.05) facilitated macrophage migration. We demonstrated that acute CCL2 stimulation promoted subsequent osteogenesis in co-culture of MSCs and macrophages. Acute CCL2 stimulation potentially facilitates osteogenesis during the acute inflammatory phase of bone healing by directing local macrophage migration, fostering macrophage-MSC crosstalk, and subsequently, by activating or licensing of MSCs by macrophage pro-inflammatory cytokines. The combination of CCL2, MSCs, and macrophages could be a potential strategy for local cell therapy in compromised bone healing.
    Type of Medium: Online Resource
    ISSN: 2296-634X
    URL: Article
    URL: Article
    DOI: 10.3389/fcell.2023.1213641
    DOI: 10.3389/fcell.2023.1213641.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2737824-X
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  • 6
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    Effect on Osteogenic Differentiation of Genetically Modified IL4 or PDGF-BB Over-Expressing and IL4-PDGF-BB Co-Over-Expressing Bone Marrow-Derived Mesenchymal Stromal Cells In Vitro
    MDPI AG ; 2021
    In:  Bioengineering Vol. 8, No. 11 ( 2021-10-29), p. 165-
    Details
    In: Bioengineering, MDPI AG, Vol. 8, No. 11 ( 2021-10-29), p. 165-
    Abstract: The use of genetically modified (GM) mesenchymal stromal cells (MSCs) and preconditioned MSCs (pMSCs) may provide further opportunities to improve the outcome of core decompression (CD) for the treatment of early-stage osteonecrosis of the femoral head (ONFH). GM interleukin-4 (IL4) over-expressing MSCs (IL4-MSCs), platelet-derived growth factor (PDGF)-BB over-expressing MSCs (PDGF-BB-MSCs), and IL4-PDGF-BB co-over-expressing MSCs (IL4-PDGF-BB-MSCs) and their respective pMSCs were used in this in vitro study and compared with respect to cell proliferation and osteogenic differentiation. IL4-MSCs, PDGF-BB-MSCs, IL4-PDGF-BB-MSCs, and each pMSC treatment significantly increased cell proliferation compared to the MSC group alone. The percentage of Alizarin red-stained area in the IL4-MSC and IL4-pMSC groups was significantly lower than in the MSC group. However, the percentage of Alizarin red-stained area in the PDGF-BB-MSC group was significantly higher than in the MSC and PDGF-BB-pMSC groups. The percentage of Alizarin red-stained area in the IL4-PDGF-BB-pMSC was significantly higher than in the IL4-PDGF-BB-MSC group. There were no significant differences in the percentage of Alizarin red-stained area between the MSC and IL4-PDGF-BB-pMSC groups. The use of PDGF-BB-MSCs or IL4-PDGF-BB-pMSCs increased cell proliferation. Furthermore, PDGF-BB-MSCs promoted osteogenic differentiation. The addition of GM MSCs may provide a useful supplementary cell-based therapy to CD for treatment of ONFH.
    Type of Medium: Online Resource
    ISSN: 2306-5354
    URL: Article
    DOI: 10.3390/bioengineering8110165
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2746191-9
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  • 7
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    Intraoperative Soft Tissue Balance/Kinematics and Clinical Evaluation of Modified Kinematically versus Mechanically Aligned Total Knee Arthroplasty
    Georg Thieme Verlag KG ; 2020
    In:  The Journal of Knee Surgery Vol. 33, No. 08 ( 2020-08), p. 777-784
    Details
    In: The Journal of Knee Surgery, Georg Thieme Verlag KG, Vol. 33, No. 08 ( 2020-08), p. 777-784
    Abstract: Recently, kinematically aligned total knee arthroplasty has been found to achieve better clinical outcomes than mechanically aligned TKA. Despite the good clinical outcomes that are reported at short- to mid-term follow-up, intraoperative variables that are associated with a better outcome have not been measured. Therefore, this study was conducted to compare intraoperative kinematics/soft tissue balance and the clinical outcomes of patients who underwent modified kinematically (restricted tibial cut) or mechanically aligned total knee arthroplasty. Sixty cruciate-retaining total knee arthroplasties (30 modified kinematically [3-degree varus and 7-degree posterior slope in tibial cut] and 30 mechanically aligned) were performed in patients with varus-type osteoarthritis using a navigation system. Intraoperative kinematics assessed by the navigation system and soft tissue balance assessed by an offset-type tensor were compared between the groups. One year postoperatively, the range of motion and 2011 Knee Society scores were compared between the groups. Kinematic assessment exhibited that tibial internal rotation during flexion was significantly maintained in the kinematic compared with the mechanical group (p  〈  0.05). Varus/valgus ligament balance at 90 and 120 degrees of flexion significantly maintained lateral laxity in the kinematic compared with the mechanical group (p  〈  0.05). Improvement of flexion angles, functional activity scores, and patient satisfaction were significantly better in the kinematic than in the mechanical group (p  〈  0.05). Modified kinematically aligned cruciate-retaining total knee arthroplasty maintained more tibial internal rotation and lateral laxity during flexion than mechanically aligned total knee arthroplasty; thus, the former may result in better clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 1538-8506 , 1938-2480
    URL: Article
    DOI: 10.1055/s-0039-1688504
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2020
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  • 8
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    Influence of Distal Reference Point of the Tibial Mechanical Axis on the Ankle and Hindlimb Alignment Change after Total Knee Arthroplasty
    Georg Thieme Verlag KG ; 2023
    In:  The Journal of Knee Surgery
    Details
    In: The Journal of Knee Surgery, Georg Thieme Verlag KG
    Abstract: The alignment philosophy in total knee arthroplasty (TKA) has tended to shift from the gold standard of mechanically aligned technique to personalized alignment, such as the kinematically aligned (KA) technique. However, the influences of different surgical techniques on lower limb alignment relative to the ground are not fully investigated. This study investigated the influence of the ankle and hindlimb alignment change after mechanically aligned TKA and KA-TKA. The varus osteoarthritic patients who underwent TKAs were divided into a mechanically aligned TKA group (group M, n = 50) and a KA-TKA group (group K, n = 50). Radiographic parameters (hip–knee–calcaneus [HKC] angle, hip–knee–ankle [HKA] angle, talar tilt angle [TTA], and tibiocalcaneal angle [TCA] ) were investigated using full-length standing radiographs. The deviation angle (ΔTA; angle between the tibial mechanical axis [TMA] and the ground tibial mechanical axis [gTMA] ) and the change of ΔTA (cΔTA) were also assessed. These parameters were compared between the two groups, along with the correlation between the preoperative HKA angle and other parameters. ΔTA, TTA, and TCA showed no differences between the groups pre- and postoperatively, and no significant changes were observed postoperatively. The preoperative HKA angle showed a significant negative correlation with cΔTA in both groups (group M: r = –0.33, p = 0.02; group K: r = –0.29, p = 0.04) although no correlation was observed the with preoperative TTA and TCA. Despite no change in ΔTA after surgery, the preoperative varus deformity was associated with a change in the deviation between gTMA and TMA after surgery. A severely varus knee may be inappropriate for ground KA-TKA.
    Type of Medium: Online Resource
    ISSN: 1538-8506 , 1938-2480
    URL: Article
    DOI: 10.1055/s-0043-1774797
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2023
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  • 9
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    MegaPro, a clinically translatable nanoparticle for in vivo tracking of stem cell implants in pig cartilage defects
    Ivyspring International Publisher ; 2023
    In:  Theranostics Vol. 13, No. 8 ( 2023), p. 2710-2720
    Details
    In: Theranostics, Ivyspring International Publisher, Vol. 13, No. 8 ( 2023), p. 2710-2720
    Type of Medium: Online Resource
    ISSN: 1838-7640
    URL: Article
    DOI: 10.7150/thno.82620
    Language: English
    Publisher: Ivyspring International Publisher
    Publication Date: 2023
    detail.hit.zdb_id: 2592097-2
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  • 10
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    Intra‐articular autologous uncultured adipose‐derived stromal cell transplantation inhibited the progression of cartilage degeneration
    Wiley ; 2019
    In:  Journal of Orthopaedic Research Vol. 37, No. 6 ( 2019-06), p. 1376-1386
    Details
    In: Journal of Orthopaedic Research, Wiley, Vol. 37, No. 6 ( 2019-06), p. 1376-1386
    Abstract: The role of uncultured adipose‐derived stromal cells for osteoarthritis treatment remains unclear despite sporadic reports supporting their use in clinical settings. This study aimed to evaluate the therapeutic effects of autologous uncultured adipose‐derived stromal cell transplantation in a rabbit osteoarthritis model. Uncultured adipose‐derived stromal cells isolated from rabbits were administered via intra‐articular injection into the knees after osteoarthritis onset. Animals were sacrificed at 8 and 12 weeks after osteoarthritis onset to compare the macroscopic, histological, and immunohistochemical characteristics between the uncultured adipose‐derived stromal cell and control groups. Co‐culture assay was also performed. The chondrocytes isolated from the model were co‐cultured with adipose‐derived stromal cells. The cell viability of chondrocytes and expression of chondrocyte‐specific genes in the co‐culture (uncultured adipose‐derived stromal cell) group were compared with the mono‐culture (control; chondrocytes only) group. In macroscopic and histological analyses, the uncultured adipose‐derived stromal cell group showed less damage to the cartilage surface than the control group at 8 and 12 weeks after osteoarthritis onset. In immunohistochemical and co‐culture assay, the uncultured adipose‐derived stromal cell group showed higher expression of collagen type II and SRY box‐9 and lower expression of matrix metalloproteinase‐13 than the control group. The cell viability of chondrocytes in the uncultured adipose‐derived stromal cell group was higher than that in the control group. Intra‐articular autologous uncultured adipose‐derived stromal cell transplantation inhibited the progression of cartilage degeneration in a rabbit osteoarthritis model by regulating chondrocyte viability and secreting chondrocyte‐protecting cytokines or growth factors, which promote anabolic factors and inhibit catabolic factors. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1376–1386, 2019.
    Type of Medium: Online Resource
    ISSN: 0736-0266 , 1554-527X
    URL: Issue
    URL: Article
    DOI: 10.1002/jorr.v37.6
    DOI: 10.1002/jor.24174
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2050452-4
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