Patent Application: US-50031706-A

Abstract:
the present invention is a method for improving cardiac function and myocardial regeneration in living subjects after the occurrence of myocardial infarction . the method is a combination stem cell therapy involving a mixture of bone marrow - derived mesenchymal stem cells and bone marrow derived mononuclear cells surgically implanted by using either a direct or catheter - mediated injection into damaged myocardium . studies have shown that the implant improves heart function and myocardial regeneration as assessed by mri , spect and echocardiographic measurements .

Description:
results of experimental studies have shown that intramyocardial implantation of autologous mononuclear bone marrow cells induces neovascularisation , but not a robust improvement in heart function , after myocardial infarction . we propose that the above therapy in conjunction with one that provides a source of cardiomyocytes will represent a substantial promise as a cellular agent for cardiovascular therapy . as a source of cardiomyocyte progenitors and based on in vitro , ex vivo and in vivo studies , we propose the use of autologous ex vivo expanded bone marrow - derived mesenchymal stem cells ( msc ). encouraging preliminary efficacy data in large animal models of myocardial infarction ( minguell , 2006 ) and accumulating safety data from human studies of mscs in non - cardiovascular applications is encouraging . in detail , our invention is the intracoronary injection ( implant via catheter or direct injection ) of a mixture of autologous bone marrow - derived mesenchymal stem cells ( bm - mscs ) ( cells that have the potential to differentiate and mature into mature cardiomyocytes ) and autologous bone marrow - derived mononuclear cells ( bm - mncs ) ( cells that contain endothelial progenitors ) that have the potential to differentiate and mature into cardiomyocytes and endothelial cells , representing an effective and enduring myocardial replacement therapy . see procedure below . primary bone marrow aspirations from the iliac crest will be performed in patients twenty - five ± five days before receiving the cell infusion for preparation and expansion of bm - msc . a secondary ( 25 ± 5 days from primary aspiration ) bone marrow aspiration from the iliac crest for preparation of bn - mnc will be performed within 5 hours of the intracoronary cell infusion to patients . for cell infusion , aliquots of autologous expanded bm - msc and bm - mnc are taken and mixed together for a final volume of infusion medium . for a better understanding of procedures and schedule , please refer to the following table . cell infusion ( transplantation ) may be done in patients intraoperatively in conjunction with coronary artery bypass grafting by direct injection following the circumference of the infarct border or via intracoronary percutaneous balloon catheter designed for angioplasty . subjects may include patients who fit criteria for acute myocardial infarction or patients with a defined region of myocardial dysfunction related to a previous myocardial infarction . wall motion and left ventricular ejection fraction is evaluated by mri and echocardiography . spect is used to assess viability and myocardial perfusion . allers c , sierralta w d , neubauer s , rivera f , minguell j j , conget p a . dynamic of distribution of human bone marrow - derived mesenchymal stem cells after transplantation into adult unconditioned mice . transplantation 78 , 503 , 2004 assmus b , schachinger v , teupe c , britten m , lehmann r , dobert n , grunwald f , aicher a , urbich c , martin h , hoelzer d , dimmeler s , zeiher a m . transplantation of progenitor cells and regeneration enhancement in acute myocardial infarction ( topcare - ami ). circulation 2002 ; 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