Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...
Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ... Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...
THE ZBOROWSKILABORATORYPROJECT SCIENTISTP. Stephen Williams, Ph.D.SENIOR RESEARCH ENGINEERLee R. MooreLEAD TECHNOLOGISTDiane R. LeighRESEARCH TECHNICIANBoris KligmanSTUDENTSLeonora Felon 1Francesca Carpino 21Co-Op Program, Univ. ofToledo, OH2Visiting graduate student,Univ. of Bologna, ItalyCOLLABORATORSBIOMEMSANDNANOTECHNOLOGYBrian J. Bolwell, M.D. 1Ernest C. Borden, M.D. 2Jeffrey J. Chalmers, Ph.D. 3Aaron Fleischman, Ph.D. 4Mauricio Hoyos, Ph.D. 5Shlomo Margel, Ph.D. 6George F. Muschler, M.D. 4Shuvo Roy, Ph.D. 4Alan N. Schechter, M.D. 71Bone Marrow Transplant.Progr., Taussig Cancer Ctr.,CCF2Dept. of Cancer Biology andTaussig Cancer Center, CCF3Dept. of Chemical Engineering,Ohio State Univ.,Columbus, OH4Dept. of Biomed. Eng., CCF5Ecole Supérieure dePhysique et ChimieIndustrielles, Paris, France6Dept. of Chemistry, Bar-IlanUniversity, Israel7Laboratory of ChemicalBiology, NIH/NIDDK,Bethesda, MD=======================Maciej Zborowski, Ph.D.=======================Our laboratory investigates novel methodsof cell separation for medical applications.The current effort focuses onmagnetic flow cell sorting, for diagnostic andtherapeutic applications. The potential diagnosticapplications include rapid screening for rare,unusual cells such as cancer cells in blood or fetalcells in maternal blood. The potential therapeuticapplications include cell therapies, such ashematopoietic (blood-forming) stem celltransplantation. Theseapplications are pursuedin collaboration with theCCF’s Taussig CancerCenter.Magnetic flowcell sorting is studied inmodel cell systems ofhuman peripherallymphocytes, culturedcell lines, and samplesdonated by patients:bone marrow, peripheralblood primed forapheresis, and umbilicalcord blood. Theadvantage of continuousmagnetic flow sorting isthat it is a high-speed,gentle process, with thepotential for highspecificity and highrecovery of sortedfractions. The specificity of sorting depends onthe specificity of the monoclonal antibodies andmagnetic agents used for cell tagging. One suchagent, an iron-doped polymeric nanoparticle, isbeing developed for magnetic cell sorting incollaboration with Bar-Ilan University in Israel.The mechanics of cell sorting in a flow, inThe Department of Biomedical EngineeringMagnetic Flow Cell Sorting Screens forCancer Cells, Offers Optionsfor Stem Cell TherapiesMaciej Zborowski, Ph.D.the presence of a magnetic field, is poorlyunderstood. We study cell motion using a uniquesystem, Cell Tracking Velocimetry (CTV),developed in collaboration with the Ohio StateUniversity. The system allows us to analyzeindividual cell velocities of hundred of cells at atime, leading to important information about thepopulation average and dispersion. The characteristiccell velocities are correlated with the physicaland biological properties of the cell, such as cellsize and cell surface markerexpression. The cell velocitiesmeasured by CTV are thebasis for the magnetic flowsorter design.The current flow sorterdesigns are based on quadrupoleand dipole magneticfields. The laboratory-scaleprototype of the quadrupolesorter produces sorting speedsin excess of a ten million cellsper second, enriches rare cellsa hundred-fold, and achievesa 70% recovery of the targetcells. The dipole cellfractionator separates cellsamples into eight fractions,characterized by different cellmobilities and different cellsurface marker expression.These capabilities areimportant in cell biologyresearch and in clinical applications. Thequadrupole sorter design is being scaled up for celltherapy applications, requiring sorting speeds onthe order of ten million cells per second, atenrichment and recovery rates comparable tothose of the laboratory prototype; the dipolefractionator design is being optimized forincreased fractionation resolution and speed.Moore, L.R., Rodriguez, A.R., Williams, P.S., McCloskey, K.E., Bolwell, B.J., Nakamura, M., Chalmers,J.J., and M. Zborowski (2001). Progenitor cell isolation with a high-capacity quadrupole magnetic flowsorter. J. Magnetism Magnetic Materials 225:277-284.Comella, K., Nakamura, M,, Melnik, K., Chosy, J., Zborowski, M., Cooper, M.A., Fehniger, T.A.,Caligiuri, M.A., and J.J. Chalmers (2001) Effects of antibody concentration on the separation of humannatural killer cells in a commercial immunomagnetic separation system. Cytometry 45:285-293.Hoyos, M., McCloskey, K.E., Moore, L.R., Nakamura, M., Bolwell, B.J., Chalmers, J.J., and M.Zborowski (2002) Pulse-injection studies of blood progenitor cells in a quadrupole magnet flow sorter.Separation Sci. Technol. 37:745-767.Zborowski, M., Moore, L.R., Williams, P.S., and J.J. Chalmers (2002) Separations based on magnetophoreticmobility. Separation Sci. Technol. 37:3611-3633.Chosy, E.J., Nakamura, M., Melnik, K., Comella, K., Lasky, L.C., Zborowski, M., and J.J. Chalmers(2003) Characterization of antibody binding to three cancer-related antigens using flow cytometry andcell tracking velocimetry. Biotechnol. Bioeng. 82:340-351.22
The Department of Biomedical EngineeringBIOMEDICALDEVICESLeonard A.R. Golding, M.D.Nonpulsatile Blood Pump at Heart of CCF’sInnovative Ventricular Assist ProgramFor nearly a quarter century, the ClevelandClinic Foundation (CCF) has been a strongcontributor in the development ofventricular assist technology. A major milestonearising from these efforts in late 1995 wasfunding from the National Heart, Lung, andBlood Institute, which awarded our collaborativeteam a contract for $4.3 million over 5years, under the Innovative Ventricular AssistSystem (IVAS) Program. The IVAS program wasa cooperative effort involving experts inindustry, academia, and clinical practice. Centralto this project is the CCF’s unique implantablecentrifugal (nonpulsatile) blood pump developedand patented in the Department of BiomedicalEngineering.The NIH program resulted in the ThirdGeneration CorAide TM Ventricular Assist System,which proved to be nonthrombogenic withoutthe use of anticoagulants. In April 2001, ArrowInternational, Inc., acquired the rights to thetechnology and is funding a 3-year program totake the system into clinical trials. The laboratoryis active in characterization system tests and finalchronic implant evaluations prior to human use.In December 2002, Arrow received regulatoryapproval in Europe for the first clinical trial ofthe device as a bridge-to-transplant/recovery.Golding, L.A., Medvedev, A., Massiello, A., Smith, W.A., Horvath, D., and R. Kasper (1998) ClevelandClinic continuous flow blood pump: progress in development. Artif. Organs 22:447-450.THE GOLDINGLABORATORYSURGICAL TEAMKazuyoshi Doi, M.D.Kiyotaka Fukamachi, M.D., Ph.D.Yoshio Ootaki, M.D., Ph.D.BIOMEDICAL ENGINEERSAlexander Massielllo, M.S.MECHANICAL ENGINEERDavid Horvath, M.S.RESEARCH TECHNICIAN/Q.A.Stephen Benefit, A.A.S.COLLABORATIONArrow International, Inc.,Reading, PA=====================LeonardA.R.Golding,M.B.,B.S.,F.R.A.C.S.,F.R.C.S.(C)=====================Golding, L., Smith, W. Horvath, D., and A. Medvedev (2000) Rotodynamic pump development. In: H.Matsuda, ed. Rotary Blood Pumps: New Developments and Current Applications. Tokyo, Japan: Springer-Verlag, pp. 47-56.Ochiai, Y., Golding, L.A., Massiello, A.L., Medvedev, A.L., Gerhart, R.L., Chen, J.F., Takagaki, M., andK. Fukamachi (2001) In vivo hemodynamic performance of the Cleveland Clinic CorAide blood pump incalves. Ann. Thorac. Surg. 72:747-752.Golding, L.A. (2002) Cleveland Clinic centrifugal blood pump. ASAIO J. 48:578; discussion 578-579.Gerhart, R.L., Horvath, D.J., Ochiai, Y., Krogulecki, A.Y., and L.A. Golding (2002) The effects of impacton the CorAide ventricular assist device. ASAIO J. 48:449-452.Fukamachi, K., Ochiai, Y., Doi, K., Massiello, A.L., Medvedev, A.L., Horvath, D.J., Gerhart, R.L., Chen,J.F., Krogulecki, A.Y., Takagaki, M., Howard, M.W., Kopcak, M.W. Jr., and L.A. Golding (2002) Chronicevaluation of the Cleveland Clinic CorAide left ventricular assist system in calves. Artif. Organs26:529-533.Ochiai, Y., Golding, L.A., Massiello, A.L., Medvedev, A.L., Horvath, D.J., Gerhart, R.L., Chen, J.F.,Krogulecki, A.Y., Takagaki, M., Doi, K., Howard, M.W., and K. Fukamachi (2002) Cleveland ClinicCorAide blood pump circulatory support without anticoagulation. ASAIO J. 48:249-252.23
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The Department of Biomedical EngineeringBIOMEDICALDEVICESLeonard A.R. Golding, M.D.Nonpulsatile Blood Pump at Heart of CCF’sInnovative Ventricular Assist ProgramFor nearly a quarter century, the <strong>Cleveland</strong><strong>Clinic</strong> Foundation (CCF) has been a strongcontributor in the development ofventricular assist technology. A major milestonearising from these efforts in late 1995 wasfunding from the National Heart, Lung, andBlood Institute, which awarded our collaborativeteam a contract for $4.3 million over 5years, under the Innovative Ventricular AssistSystem (IVAS) Program. The IVAS program wasa cooperative effort involving experts inindustry, academia, and clinical practice. Centralto this project is the CCF’s unique implantablecentrifugal (nonpulsatile) blood pump developedand patented in the Department of BiomedicalEngineering.The NIH program resulted in the ThirdGeneration CorAide TM Ventricular Assist System,which proved to be nonthrombogenic withoutthe use of anticoagulants. In April 2001, ArrowInternational, Inc., acquired the rights to thetechnology and is funding a 3-year program totake the system into clinical trials. The laboratoryis active in characterization system tests and finalchronic implant evaluations prior to human use.In December 2002, Arrow received regulatoryapproval in Europe for the first clinical trial ofthe device as a bridge-to-transplant/recovery.Golding, L.A., Medvedev, A., Massiello, A., Smith, W.A., Horvath, D., and R. Kasper (1998) <strong>Cleveland</strong><strong>Clinic</strong> continuous flow blood pump: progress in development. Artif. Organs 22:447-450.THE GOLDINGLABORATORYSURGICAL TEAMKazuyoshi Doi, M.D.Kiyotaka Fukamachi, M.D., Ph.D.Yoshio Ootaki, M.D., Ph.D.BIOMEDICAL ENGINEERSAlexander Massielllo, M.S.MECHANICAL ENGINEERDavid Horvath, M.S.RESEARCH TECHNICIAN/Q.A.Stephen Benefit, A.A.S.COLLABORATIONArrow International, Inc.,Reading, PA=====================LeonardA.R.Golding,M.B.,B.S.,F.R.A.C.S.,F.R.C.S.(C)=====================Golding, L., Smith, W. Horvath, D., and A. Medvedev (2000) Rotodynamic pump development. In: H.Matsuda, ed. Rotary Blood Pumps: New Developments and Current Applications. Tokyo, Japan: Springer-Verlag, pp. 47-56.Ochiai, Y., Golding, L.A., Massiello, A.L., Medvedev, A.L., Gerhart, R.L., Chen, J.F., Takagaki, M., andK. Fukamachi (2001) In vivo hemodynamic performance of the <strong>Cleveland</strong> <strong>Clinic</strong> CorAide blood pump incalves. Ann. Thorac. Surg. 72:747-752.Golding, L.A. (2002) <strong>Cleveland</strong> <strong>Clinic</strong> centrifugal blood pump. ASAIO J. 48:578; discussion 578-579.Gerhart, R.L., Horvath, D.J., Ochiai, Y., Krogulecki, A.Y., and L.A. Golding (2002) The effects of impacton the CorAide ventricular assist device. ASAIO J. 48:449-452.Fukamachi, K., Ochiai, Y., Doi, K., Massiello, A.L., Medvedev, A.L., Horvath, D.J., Gerhart, R.L., Chen,J.F., Krogulecki, A.Y., Takagaki, M., Howard, M.W., Kopcak, M.W. Jr., and L.A. Golding (2002) Chronicevaluation of the <strong>Cleveland</strong> <strong>Clinic</strong> CorAide left ventricular assist system in calves. Artif. Organs26:529-533.Ochiai, Y., Golding, L.A., Massiello, A.L., Medvedev, A.L., Horvath, D.J., Gerhart, R.L., Chen, J.F.,Krogulecki, A.Y., Takagaki, M., Doi, K., Howard, M.W., and K. Fukamachi (2002) <strong>Cleveland</strong> <strong>Clinic</strong>CorAide blood pump circulatory support without anticoagulation. ASAIO J. 48:249-252.23
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