The “MarrowMiner”: A Novel, Minimally Invasive Device for the Harvest of Bone Marrow: Initial Human Experience Reveals Safety, Efficacy and Richer Cell Product Than Standard Harvest Methods

Abstract

INTRODUCTION: Bone marrow (BM) contains a rich supply of adult stem and progenitor cells, including hematopoieitic and mesenchymal stem cells which are used in Bone Marrow Transplantation (BMT) and an increasing array of regenerative therapies. Traditional marrow harvest methods utilize percutaneous large bore needle aspiration, result in marrow highly diluted by peripheral blood, and are crude, tedious, labor intensive and expensive, usually requiring general anesthesia, and >100 serial small volume aspirates to obtain adequate cell numbers for BMT. BM is showing increasing long-term advantages over mobilized PBSC for many alloegeneic BMTs, in terms of less cGVHD and in some cases improved survival. Improved BM harvest methods are needed. A novel device, the “MarrowMiner” (MM), was developed for the minimally invasive harvest of BM to enable the rapid, convenient, outpatient harvest of large quantities of BM under local anesthesia for use in allogeneic and autologous BMT and cell therapies utilizing autologous marrow derived cells. The MarrowMiner utilizes a single marrow entry site into the anterior or posterior iliac, through which the flexible, powered, guidable FlexShaft catheter can access the majority of the marrow space and aspirate rich marrow. Extensive testing in human cadavers and porcine models demonstrated a 10X increase in stem cells activity/ml (by CFU) compared to that of traditional needle harvests. The MM recently received both FDA and CE Mark regulatory approved, and ‘First In Human’ trials were successfully completed under local anesthesia, demonstrating safety, efficacy and higher stem cell yields compared to traditional methods.METHODS: In an ongoing prospective study, 10 patients undergoing autologous marrow derived therapy for use in regenerative medicine, had marrow harvested from their anterior or posterior ileac by the MM under local anesthesia on one hip, with direct comparison to standard needle serial marrow aspirates on the patients opposite hip (up to 350 ml per side). Cell viability, counts, CD34+, T cell, and MSC populations were assessed by flow cytometry.RESULTS: The MM successfully harvested marrow from a single entry sites and 2–3 paths under local anesthesia, without complications. Compared to standard harvest in the same patients, MM harvests had significantly number of Total Nucleated Cells ml compared to marrow harvested from the same patient by standard needle ( mean 1.98 fold greater TNC (range 0.87–3.36, p<.05). Viability was equivalent at (>99). In addition to higher TNC/ml, significantly higher levels (mean 3.56 fold) of Aldeflour/ALDH+ cells/ml, CD34+, and phenotypic MSC (CD45−,34−,90+,105+) and endothelial progenitor cells were obtained, as measured by flow cytometry. Mean CD3+ T-cell counts per ml were lower with MM harvests.CONCLUSIONS: The novel FDA approved MarrowMiner system demonstrated safety and efficacy in clinical use, harvesting more stem cells per unit volume in a single entry compared to standard harvest methods. These results suggests the MM may enable improved clinical stem cell harvests in a more rapid and minimally invasive manner in the outpatient setting, while harvesting a richer marrow product with less peripheral blood contamination. Such a system, facilitating convenient, on demand stem cell collection may have significant application for BMT and other marrow based cellular therapies.