title: Circular Halbach array for fast magnetic separation of hyaluronan-expressing tissue progenitors.
abstract: Connective tissue progenitors (CTPs) are a promising therapeutic agent for bone repair. Hyaluronan, a high molecular mass glycosaminoglycan, has been shown by us to be a suitable biomarker for magnetic separation of CTPs from bone marrow aspirates in a canine model. For the therapy to be applicable in humans, the magnetic separation process requires scale-up without compromising the viability of the cells. The scaled-up device presented here utilizes a circular Halbach array of diametrically magnetized, cylindrical permanent magnets. This allows precise control of the magnetic field gradient driving the separation, with theoretical analysis favoring a hexapole field. The separation vessel has the external diameter of a 50 mL conical centrifuge tube and has an internal rod that excludes cells from around the central axis. The magnet and separation vessel (collectively dubbed the hexapole magnet separator or HMS) was tested on four human and four canine bone marrow aspirates. Each CTP-enriched cell product was tested using cell culture bioassays as surrogates for in vivo engraftment quality. The magnetically enriched cell fractions showed statistically significant, superior performance compared to the unenriched and depleted cell fractions for all parameters tested, including CTP prevalence (CTPs per 10(6) nucleated cells), proliferation by colony forming unit (CFU) counts, and differentiation by staining for the presence of osteogenic and chondrogenic cells. The simplicity and speed of the HMS operation could allow both CTP isolation and engraftment during a single surgical procedure, minimizing trauma to patients and lowering cost to health care providers.
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: Powrnima
authors.initials: P
authors.lastname: Joshi
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.|Cambrian Technologies, Inc. , 1772 Saratoga Avenue, Cleveland, Ohio 44109, United States.
authors.forename: P Stephen
authors.initials: PS
authors.lastname: Williams
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: Lee R
authors.initials: LR
authors.lastname: Moore
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: Tonya
authors.initials: T
authors.lastname: Caralla
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Boehm
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.|Orthopedic and Rheumatologic Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: George
authors.initials: G
authors.lastname: Muschler
authors.affiliation: Department of Biomedical Engineering, Lerner Research Institute, Cleveland Clinic , 9500 Euclid Avenue, Cleveland, Ohio 44195, United States.
authors.forename: Maciej
authors.initials: M
authors.lastname: Zborowski
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002454:Cell Differentiation; D002469:Cell Separation / Q000295:instrumentation*; D002478:Cells, Cultured; D004285:Dogs; D004867:Equipment Design; D006801:Humans; D006820:Hyaluronic Acid / Q000032:analysis*; D008280:Magnetics / Q000295:instrumentation*; D013234:Stem Cells / Q000166:cytology
chemical_list: D006820:Hyaluronic Acid