Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration

Dawson, Jonathan I.; Smith, James O.; Aarvold, Alexander; Ridgway, Jonathan; Curran, Steven J.; Dunlop, D.G.; Oreffo, Richard O.C.

doi:10.1016/j.jcyt.2012.09.004

Cited by 27 publications

(30 citation statements)

References 52 publications

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“…Besides, the preservation rate of bone volume fraction of the subarticular spongiosa of defect region following microfracture was also significantly improved by addition of bone marrow aspirate. These data suggest a protective effect of the bone marrow aspirate on the subchondral bone, especially the subarticular spongiosa, which is also consistent with previous studies on the osteogenic effect of bone marrow aspirate in fracture and osteonecrosis treatments92627. It is possible that the bone marrow aspirate protected the openings of the microfracture holes towards the joint space from the aggressive synovial fluid, thereby additionally favoring new tissue formation4828.…”

Section: Discussionsupporting

confidence: 90%

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

Gao

Orth

Müller-Brandt

et al. 2017

Sci Rep

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Microfracture of cartilage defects may induce alterations of the subchondral bone in the mid- and long-term, yet very little is known about their onset. Possibly, these changes may be avoided by an enhanced microfracture technique with additional application of bone marrow aspirate. In this study, full-thickness chondral defects in the knee joints of minipigs were either treated with (1) debridement down to the subchondral bone plate alone, (2) debridement with microfracture, or (3) microfracture with additional application of bone marrow aspirate. At 4 weeks after microfracture, the loss of subchondral bone below the defects largely exceeded the original microfracture holes. Of note, a significant increase of osteoclast density was identified in defects treated with microfracture alone compared with debridement only. Both changes were significantly counteracted by the adjunct treatment with bone marrow. Debridement and microfracture without or with bone marrow were equivalent regarding the early cartilage repair. These data suggest that microfracture induced a substantial early resorption of the subchondral bone and also highlight the potential value of bone marrow aspirate as an adjunct to counteract these alterations. Clinical studies are warranted to further elucidate early events of osteochondral repair and the effect of enhanced microfracture techniques.

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Section: Discussionsupporting

confidence: 90%

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

Gao

Orth

Müller-Brandt

et al. 2017

Sci Rep

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“…We also demonstrated that platelets were concentrated 4.5-fold, showing an additional value of unfractionated bone marrow concentrates with respect to providing growth factors 42 . Compared with our data, Dawson et al demonstrated a 4-fold increase of CTPs in bone marrow concentrates 43 . Another recent study showed that 2 concentrator devices produced substantially different counts of CTPs and dissimilar levels of growth factors 44 .…”

Section: Discussioncontrasting

confidence: 80%

The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful Measurement of the Bone Marrow Quality for Cartilage and Bone Regenerative Therapy

El-Jawhari

Cuthbert

McGonagle

et al. 2017

The Journal of Bone and Joint Surgery

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Background:Bone marrow aspirates and concentrates are increasingly being used for musculoskeletal regenerative therapies, providing bone and cartilage progenitors. However, the quality of these bone marrow samples remains imprecise within clinical settings. As there is a need for the development of these therapies, a method of counting CD45lowCD271high cells was optimized and tested as an indicator of bone marrow sample quality.Methods:Bone marrow aspirates were collected from 54 donors (28 male and 26 female; median age of 48 years). The reagent concentrations were optimized for fast staining, and an acoustic-focusing flow cytometer (Attune) was used to enable automated CD45lowCD271high cell counting in bone marrow aspirates, bone marrow concentrates, and samples loaded onto a collagen scaffold. The CD45lowCD271high cell counts were compared with those obtained using another flow-cytometry-based method (LSR II) and with connective tissue progenitor (CTP) counts quantified using a colony forming unit-fibroblast (CFU-F) assay.Results:The optimized method enabled the counting of CD45lowCD271high cells within only 15 minutes. The quantified cell counts (median, 1,520; range, 96 to 20,992 cells/mL of bone marrow) were positively correlated with the CTP counts (p < 0.0001; r = 0.7237). In agreement with CFU-F and LSR II-based assays, the CD45lowCD271high cell counts quantified using the Attune-based method decreased with age in the samples from female but not male donors (p = 0.0015 and p = 0.3877, respectively). A significant increase in CD45lowCD271high cell counts was detected following bone marrow concentration (mean, 5-fold; 95% confidence interval [CI], 3.6 to 7.2-fold). Additionally, the number of CD45lowCD271high cells attached to the collagen scaffold was positively correlated with the number of progenitor cells that survived on the scaffold after 2-week culture (p = 0.0348).Conclusions:An assay for counting CD45lowCD271high cells may provide a useful measurement of bone marrow quality. While the specificity of this measurement of CD45lowCD271high cells remained low in our experimental conditions, CD45lowCD271high cell counts were positively and modestly correlated with the prevalence of CTPs.Clinical Relevance:A fast and automated assessment of bone marrow aspirate/concentrate quality using CD45lowCD271high cell counting may be a useful tool for improving the quality of regenerative therapy.

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“…Our data are comparable to the number of progenitors reported by Dawson et al who found a 3.1-fold MSC progenitors concentration after filtration using the BMAC system. 26 Indeed, our results assure an effective concentration of CTP, from which MSC originate, that exceed the therapeutic threshold of 1000 CFU-F/mL suggested by Hernigou et al 27 In fact, data from literature showed that the efficiency of a cell-based treatment depends largely on the number of MSC progenitors usually analysed by the CFU-assay. We used 0.2 mL of BMC to prepare the injectable MBS, around 2 3 10 3 MSC progenitors.…”

Section: Discussionsupporting

confidence: 64%

Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel‐coated OSPROLIFE^® HA/TTCP granules and bone marrow concentrate

et al. 2015

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The purpose of this study was to examine the in vitro cytocompatibility of a novel injectable multiphasic bone substitute (MBS) based on polysaccharide gel-coated OSPROLIFE(®) hydroxyapatite (HA)/tetracalcium phosphate (TTCP) granules combined with bone marrow concentrate (BMC). Polysaccharide gel-coated granules loaded in syringe were combined with BMC diluted in ionic crosslinking solution. The product was then maintained in culture to investigate the cytocompatibility, distribution, and osteogenic differentiation function of cells contained in the BMC. The in vitro cytocompatibility was assessed after 0, 24, and 96 h from the injectable MBS preparation using the LIVE/DEAD(®) staining kit. The results highlighted that cells remained viable after combination with the polysaccharide gel-coated granules; also, viability was maintained over time. The distribution of the cells in the product, observed using confocal microscopy, showed viable cells immersed in the polysaccharide gel formed between the granules after ionic crosslinking. The mesenchymal stromal cells (MSC) contained in the injectable MBS, the basic elements for bone tissue regeneration, were able to differentiate toward osteoblasts, producing an osteogenic matrix as evidenced by alizarin red-s (AR-S) staining. In conclusion, we found that the injectable MBS may have the potential to be used as a bone substitute by applying a "one-step" procedure in bone tissue engineering applications. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 894-902, 2016.

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Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration

Abstract: These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing.

Cited by 27 publications

References 52 publications

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful Measurement of the Bone Marrow Quality for Cartilage and Bone Regenerative Therapy

Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel‐coated OSPROLIFE^® HA/TTCP granules and bone marrow concentrate

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Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration

Abstract: These studies provide evidence for the importance of BMA nucleated cell concentration for both cell differentiation and cell seeding efficiency and demonstrate the potential of this approach for intraoperative application to enhance bone healing.

Cited by 27 publications

References 52 publications

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

Early loss of subchondral bone following microfracture is counteracted by bone marrow aspirate in a translational model of osteochondral repair

The CD45lowCD271high Cell Prevalence in Bone Marrow Samples May Provide a Useful Measurement of the Bone Marrow Quality for Cartilage and Bone Regenerative Therapy

Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel‐coated OSPROLIFE® HA/TTCP granules and bone marrow concentrate

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Characterization and cytocompatibility of a new injectable multiphasic bone substitute based on a combination of polysaccharide gel‐coated OSPROLIFE^® HA/TTCP granules and bone marrow concentrate