Novel technology to provide an enriched therapeutic cell concentrate from bone marrow aspirate

Abstract

Current strategies to repair fractures rely on orthopaedic surgeons harvesting bone from one area of the body, typically pelvis and transferring it to the fracture site. The amount of tissue available is therefore limited, requiring a second surgical procedure and often causing the patient long term pain. An alternative approach is utilise therapeutic cells contained within bone marrow aspirate during the primary procedure. The number of therapeutic cells within a fresh aspirate is insufficient to provide clinically acceptable bone healing in a timescale that is satisfactory to the surgeon and the patient. Therefore methods to efficiently concentrate bone marrow in the clinical setting are required. Centrifugation is the current method of choice but has limitations in that it requires large capital equipment, servicing and there are potential issues of tissue contamination. We have developed a novel, acoustically-assisted filtration device that addresses these limitations, delivering a concentrated bone marrow in a point of care, single use, fully disposable, compact device. An additional advantage is that the level of concentration required can be specified by the end user. The resulting bone marrow concentrate has been characterised in terms of cell number, viability and osteogenic potential using flow cytometry and alkaline phosphatase assay. When compared to recent clinical studies using bone marrow to repair non-union fractures, the findings from our work suggest that the bone marrow concentrate is likely to be highly therapeutic and clinically efficacious as a bone fracture repair strategy. A product concept for use in the clinical setting is presented.

Means of enhancing bone fracture healing: optimal cell source, isolation methods and acoustic stimulation

“…Therefore, we propose a different approach: the delivery of acoustic stimulated BM from the ilium (rich in hMSCs) at the fracture site. Based on a previous study by Ridgway J. et al, where acoustic vibration was used to separate cells from BM suspension, by trapping the cells in the pressure node planes of the standing wave and reducing the volume, an increase in CFU-Ob potential was observed in the processed BM [22]. We believe that this increase was not only due to the reduction in BM volume but also a change in cell fate.…”

“…[22]. BM was placed into the processing chamber of the device and acoustic vibration was applied using a voice-coil which produced a geometric standing waveform pattern on the BM fluid surface.…”

Repair Potential of Matrix-Induced Bone Marrow Aspirate Concentrate and Matrix-Induced Autologous Chondrocyte Implantation for Talar Osteochondral Repair

“…25 However, the limitations of this strategy, such as the great number of cells required that needs laboratory expansion and manipulation, as well as the patient burden and high costs, moved the field of the research toward the development of single-stage approaches. To this end, the use of bone marrow aspirate concentrate, obtained directly in the operating theatre via the use of specific devices, 26,27 opened new perspectives in the orthopedic field, reducing the aforementioned problems. [34][35][36] Indeed, the promising results obtained by in vitro and in vivo studies on BMC, indicating its ability to differentiate cartilage and osteochondral lineage 37 and to contribute to cartilage repair, 38,39 support the idea of using mBMAC in filling osteochondral defects promoting tissue repair.…”

“…[18][19][20] Subsequently, more attention has been directed toward the importance of using different cell types, wherein the application of mesenchymal stem cells (MSC) [21][22][23][24] covered a noticeable interest because of their ability to differentiate towards chondrogenic and osteogenic lineages as well as their ability of secreting a wide amount of growth factors and cytokines. 25 Lately, increasing research studies have been focused on the use of "onestep" surgical techniques, such as Bone Marrow Aspirate Concentration (BMAC), [26][27][28] thus allowing easy handling, no cell manipulation, and a large number of cells for the repair of large cartilage defects, resulting in a less expensive strategy compared to other therapeutic strategies.…”

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

“…These techniques have shown proven benefits in vitro (48,49), in animal models (50,51) and in a variety of different clinical indications including osseous defects, osteonecrosis, osteoarthritis and peripheral vascular disease (11,20,23,43,52,53). However, despite the success of this technique, centrifugation approaches entail considerable capital equipment expenditure and, due to their size and lack of sterility, preclude BMA concentration within the surgical field risking infection as well as donor cross-contamination (24,28). We have presented an efficient and inexpensive solution to cell enrichment amenable for development toward a single-use device and able to be applied intraoperatively within the sterile field, offering considerable potential for clinical benefit.…”