Patent Abstract:
the present invention is a method for improving cardiac and / or cardiovascular functions in living subjects after the occurrence of a myocardial and / or cardiovascular disorder , involving tissue damage and / or an ischemic event . 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 tissue . studies have shown that the implant improves blood perfusion in an ischemic tissue and thus contributes to the recovery of cardiac and / or cardiovascular function as assessed by methods of choice , including magnetic resonance imaging , echocardiography , angiography and 99mtc - tf perfusion scintigraphy .

Detailed Description:
results of experimental and clinical studies have shown that implantation of autologous bone marrow derived mononuclear cells (“ bm - mnc ”) induces neovascularisation , but not a robust improvement in tissue function , after mi and / or a cardiovascular disorder . in an embodiment of the present invention , we propose that the above therapy in conjunction with one that provides a source of cardiomyocytes and / or endothelial repair cells will represent a substantial promise as a cellular agent for cardiovascular therapy . as a source of cardiomyocyte and / or endothelial repair progenitors and based on in vitro , ex vivo and in vivo studies , the present invention utilizes autologous or allogeneic ex vivo - expanded bone marrow - derived mesenchymal stem cells . 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 one example though non - limiting embodiment , the intracoronary injection ( implant via catheter or direct injection ) of a mixture of autologous or allogeneic bm - mscs and autologous bm - mncs represents an effective and enduring myocardial and / or cardiovascular replacement therapy . mscs are not immunologically rejective , and , thus , do not need to come from the patient &# 39 ; s bone marrow , but can instead come from a suitable human donor . in an example embodiment , primary bone marrow aspirations from the iliac crest will be performed in the patient or a suitable donor twenty - five ± five days before the patient is to receive the cell infusion . during the time between aspiration and infusion , the bm - mscs will be prepared through ex vivo expansion and purification , until a therapeutically effective amount is obtained . in another example though non - limiting embodiment , a secondary bone marrow aspiration will be performed in patients twenty - five ± five days after the primary aspiration from the iliac crest . this aspiration is used for preparation of bm - mncs and is performed , in an example embodiment , within five hours of the cell infusion to the patient . this example embodiment does not require purification or expansion of the endothelial progenitor cells , but instead , the content of endothelial progenitor cells biologically present in the bone marrow mononuclear cell fraction is used . for cell infusion , aliquots of autologous or allogeneic expanded bm - mscs and autologous bm - mncs are mixed together for a final solution of infusion medium . in analyzing the bone marrow mononuclear cell fraction , to ensure a therapeutically effective amount of bm - mncs was obtained in the second aspiration , a method known in the art is used to count the number of endothelial progenitor cells present in the bm - mnc fraction . endothelial progenitor cells have a unique ligand configuration in the cell membrane which allows the preparer to easily and quickly ascertain the number of endothelial progenitor cells present in the aspiration . for a better understanding of the above - described procedures and schedule , refer to table 1 below . in an example embodiment , cell infusion ( transplantation ) is completed in myocardial infarct 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 . in other example embodiments , cell infusion ( transplantation ) is completed in cd patients by injecting the cell mixture intracoronarily ( by the use of a catheter ), intracardially ( directly into the heart ) or intramusculary ( in the arm , leg , etc in close proximity to an ischemic region without proper blood supply ). subjects may include patients who fit criteria for cardiovascular dysfunction associated with the existence of ischemic regions . improvement in function and tissue perfusion is evaluated by magnetic resonance imaging (“ mri ”), echocardiography , angiography and 99mtc - tf perfusion scintigraphy . methods of cd replacement therapy for a patient are disclosed . the methods involve acquiring two types of bone marrow - derived cells —( 1 ) a therapeutically effective amount of autologous or allogeneic mesenchymal stem cells that give rise to cardiomyocytes and / or endothelial repair cells and ( 2 ) a source of endothelial progenitor cells present as such , in the bone marrow - derived mononuclear cell fraction , that may give rise to new blood vessels . the therapeutically effective amount of mesenchymal stem cells and mononuclear cells are combined into an injection medium and the resulting mixture is injected into the patient . this method may be used wherein the step of acquiring a therapeutically effective amount of autologous or allogeneic mesenchymal stem cells that give rise to cardiomyocytes and / or endothelial repair cells comprises performing a first bone marrow aspiration on the patient or other suitable human donor and producing a therapeutically effective amount of expanded bone marrow - derived mesenchymal stem cells , wherein the first bone marrow aspiration is performed at least twenty - five ( 25 ) days before the patient receives said injection medium . alternatively , the first aspiration may be performed a sufficient amount of time before the injection , allowing enough time to expand the bm - mscs until the therapeutically effective amount is reached . further , the present invention for myocardial and / or cardiovascular replacement therapy includes acquiring a source of a therapeutically effective amount of the autologous expanded bone marrow - derived mononuclear cells as a source of endothelial progenitor cells and comprises performing a second bone marrow aspiration from the patient &# 39 ; s iliac crest on the day when the patient is to receive the injection medium , preferably , though not limited to , five hours before the patient is to receive the injection medium . as another alternate , the second aspiration may be performed on the day when it is determined that the amount of mesenchymal stem cells is sufficient to produce the therapeutically effective amount of mesenchymal stem cells needed for the treatment , and not necessarily five hours prior to the infusion . in another example though non - limiting embodiment , the method may be used not only for treatment of mi , but also for other cd , like : ( 1 ) vascular blood flow restoration ; ( 2 ) increased blood flow supply due to vascular damage ; and ( 3 ) capillary recruitment for severe vascular compromise . while a number of example embodiments of the present invention have been described , it is understood that these example embodiments are illustrative only , and not restrictive , and that many modifications would be apparent to those of ordinary skill in the art . 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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