Mesenchymal stem cells and porous β-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia

Chu, Wenxiang; Gan, Yaokai; Zhuang, Yifu; Wang, Xin; Zhao, Jie; Tang, Tingting; Dai, Kerong

doi:10.1186/s13287-018-0906-1

Cited by 31 publications

(30 citation statements)

References 43 publications

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“…Until now, no reliable conclusion was found to explain the greater retaining of MSCs to carrier materials compared to other nuclear cells. Chu et al (2018) showed that filtration of bone marrow cells through various BSMs led to an enrichment of MSCs and their direct adhesion to the surfaces of porous BSM [53]. Importantly, the filtration enrichment method allows MSC concentration without interference from exogen agents, revealing no significant changes in phenotypic characteristics of the MSCs, osteogenetic fate, specific antigens, gene expression profile, cell cycle stage and apoptosis rate compared to before filtration [37,44].…”

Section: Conditioning Systems Composites and Growth Factorsmentioning

confidence: 99%

Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment

Busch

Herten

Haversath³

et al. 2020

IJMS

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During total joint replacement, high concentrations of mesenchymal stromal cells (MSCs) are released at the implantation site. They can be found in cell–tissue composites (CTC) that are regularly removed by surgical suction. A surgical vacuum suction handle was filled with bone substitute granules, acting as a filter allowing us to harvest CTC. The purpose of this study was to investigate the osteopromotive potential of CTC trapped in the bone substitute filter material during surgical suction. In the course of 10 elective total hip and knee replacement surgeries, β-tricalcium-phosphate (TCP) and cancellous allograft (Allo) were enriched with CTC by vacuum suction. Mononuclear cells (MNC) were isolated from the CTC and investigated towards cell proliferation and colony forming unit (CFU) formation. Furthermore, MSC surface markers, trilineage differentiation potential and the presence of defined cytokines were examined. Comparable amounts of MNC and CFUs were detected in both CTCs and characterized as MSC‰ of MNC with 9.8 ± 10.7‰ for the TCP and 12.8 ± 10.2‰ for the Allo (p = 0.550). CTCs in both filter materials contain cytokines for stimulation of cell proliferation and differentiation (EGF, PDGF-AA, angiogenin, osteopontin). CTC trapped in synthetic (TCP) and natural (Allo) bone substitute filters during surgical suction in the course of a joint replacement procedure include relevant numbers of MSCs and cytokines qualified for bone regeneration.

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Section: Conditioning Systems Composites and Growth Factorsmentioning

confidence: 99%

Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment

Busch

Herten

Haversath³

et al. 2020

IJMS

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“…The benefits of MSC therapy are mainly attributed to paracrine effects via soluble factors, exerting both immunoregulatory and regenerative actions [11]. Although implanted MSC may act as osteoprogenitors [12][13][14], most evidence indicates that newly formed bone is mainly derived from host progenitors. The mechanisms by which macrophages contribute to MSC-mediated tissue repair remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Influence of inflammatory conditions provided by macrophages on osteogenic ability of mesenchymal stem cells

et al. 2020

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Background: The mechanisms by which macrophage phenotype contributes to mesenchymal stem cells (MSC)mediated bone repair remain unclear. In this work, we investigated the influence of factors released by human macrophages polarized to a pro-inflammatory or an anti-inflammatory phenotype on the ability of human MSC to attach, migrate, and differentiate toward the osteoblastic lineage. We focused on the role of TNF-α and IL-10, key pro-inflammatory and anti-inflammatory cytokines, respectively, in regulating MSC functions. Methods: MSC were treated with media conditioned by pro-inflammatory or anti-inflammatory macrophages to study their influence in cell attachment, migration, and osteogenic differentiation. The involvement of TNF-α and IL-10 in the regulation of MSC functions was investigated using neutralizing antibodies and recombinant cytokines. Results: Treatment of MSC with media conditioned by pro-inflammatory or anti-inflammatory macrophages promoted cell elongation and enhanced MSC ability to attach and migrate. These effects were more noticeable when MSC were treated with media from pro-inflammatory macrophages. Interestingly, MSC osteogenic activity was enhanced by factors released by anti-inflammatory macrophages, but not by pro-inflammatory macrophages. Significant IL-10 levels originated from anti-inflammatory macrophages enhanced MSC osteogenesis by increasing ALP activity and mineralization in MSC layers cultured under osteogenic conditions. Moreover, macrophage-derived IL-10 regulated the expression of the osteogenic markers RUNX2, COL1A1, and ALPL. Notably, low TNF-α levels secreted by anti-inflammatory macrophages increased ALP activity in differentiating MSC whereas high TNF-α levels produced by pro-inflammatory macrophages had no effects on osteogenesis. Experiments in which MSC were treated with cytokines revealed that IL-10 was more effective in promoting matrix maturation and mineralization than TNF-α. Conclusions: Factors secreted by pro-inflammatory macrophages substantially increased MSC attachment and migration whereas those released by anti-inflammatory macrophages enhanced MSC osteogenic activity as well as cell migration. IL-10 was identified as an important cytokine secreted by anti-inflammatory macrophages that potentiates MSC osteogenesis. Our findings provide novel insights into how environments provided by macrophages regulate MSC osteogenesis, which may be helpful to develop strategies to enhance bone regeneration.

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“…The SECCS we developed previously can rapidly incorporate processes of screening, enrichment of autologous bone marrow MSCs and generation of composites with porous bone substitutes intraoperatively. These composites have shown superior osteogenic effects in animal models and clinical patients [10,25]. In this study, the number of MSCs in bone marrow was signi cantly decreased after treatment with SECCS, indicating that MSCs successfully adhered to the porous β-TCP.…”

Section: Discussionmentioning

confidence: 52%

“…Preparation and characterisation of MSCs/β-TCP The mixture of MSCs/β-TCP was prepared by SECCS, as previously reported [10]. Brie y, after the goat was fully anaesthetised, approximately 55 ml of bone marrow was taken from the bilateral anterior superior iliac spines.…”

Section: Fabrication Of Ti6al4v Frame and Rounding Of Its Distal Surfacementioning

confidence: 99%

“…At present, the insu cient amount of autologous bone and limited osteogenic ability of conventional bone substitutes have led to research efforts aimed at identifying bone llings with excellent osteogenic properties [7][8][9]. The stem cell Screen-Enrich-Combine(-biomaterials) Circulating System (SECCS), developed previously by us, can rapidly prepare enriched mesenchymal stem cells (MSCs)/beta tricalcium phosphate (β-TCP) composites, which have shown good bone repair ability in animal and various clinical bone defect models [10,11]. However, the e cacy of repair needs to be further veri ed as an in-frame lling to repair complex anatomical bone defects.…”

Section: Introductionmentioning

confidence: 99%

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Use of a novel Screen–Enrich–Combine(-biomaterials) Circulating System for filling of a 3D-printed open Ti6Al4V frame with mesenchymal stem cells/β-tricalcium phosphate to repair complex anatomical bone defects in load-bearing areas

Chu

Liu

Gan

et al. 2020

Preprint

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Background: Repairing complex anatomical load-bearing bone defects is difficult because it requires restoration of load-bearing function, reconstruction of anatomical shape and repair by regenerated bone. We previously developed a Screen–Enrich–Combine(-biomaterials) Circulating System (SECCS) for rapid intraoperative enrichment of autologous bone marrow mesenchymal stem cells (MSCs) to enhance the osteogenic ability of porous bone substitutes. In this study, we prepared a 3D-printed Ti6A14V macroporous frame matching the defect shape to provide early load-bearing support and evaluated the efficacy of filling the frame with SECCS-processed MSCs/beta tricalcium phosphate (β-TCP) for long-term bone growth. Method: Mechanical testing of the cylindrical Ti6Al4V frame identified optimal 3D printing parameters. The lateral part of a goat distal femur was used as the defect model, and a matching electron beam melting technology-prepared (EBM) Ti6Al4V frame was fitted. Three frames filled with nothing, pure porous β-TCP or SECCS-processed MSCs/β-TCP were fixed onto the defect site. Repair efficacy was evaluated by X-ray radiography, computed tomography, histology and histomorphology. Results: In the basic regular hexagon printing unit, the combined side width (w) and inscribed circle diameter (d) determines the printing frame’s mechanical strength. The compressive load was significantly higher for w = 1.9 mm, d = 4.4 mm than for w = 1.7 mm, d = 4.0 mm or w = 2.0 mm, d = 5.0 mm (P < 0.05). The EBM-prepared Ti6Al4V defect-matched frame was well maintained 9 months after implantation. The MSCs successfully adhered to the wall of the porous β-TCP in the SECCS-processed group and had spread fully in the test samples. Each goat in the MSCs/β-TCP–filling group had approximately 31,321.7 ± 22,554.7 MSCs and a larger area of new bone growth inside the frame than the areas in the control and blank groups.Conclusion: Filling the 3D-printed Ti6Al4V large-aperture frame with osteogenic materials achieved biological reconstruction over a larger area of regenerated bone for repair of complex anatomical weight-bearing bone defects under the condition of early frame-supported load bearing. MSCs/β-TCP prepared by SECCS can be used as a filling material for this type of bone defect to obtain more efficacious bone repair.

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Mesenchymal stem cells and porous β-tricalcium phosphate composites prepared through stem cell screen-enrich-combine(−biomaterials) circulating system for the repair of critical size bone defects in goat tibia

Cited by 31 publications

References 43 publications

Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment

Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment

Influence of inflammatory conditions provided by macrophages on osteogenic ability of mesenchymal stem cells

Use of a novel Screen–Enrich–Combine(-biomaterials) Circulating System for filling of a 3D-printed open Ti6Al4V frame with mesenchymal stem cells/β-tricalcium phosphate to repair complex anatomical bone defects in load-bearing areas

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