Background-Experimental data suggest that bone marrow-derived cells may contribute to the healing of myocardial infarction (MI). For this reason, we analyzed 10 patients who were treated by intracoronary transplantation of autologous, mononuclear bone marrow cells (BMCs) in addition to standard therapy after MI. Methods and Results-After standard therapy for acute MI, 10 patients were transplanted with autologous mononuclear BMCs via a balloon catheter placed into the infarct-related artery during balloon dilatation (percutaneous transluminal coronary angioplasty). Another 10 patients with acute MI were treated by standard therapy alone. After 3 months of follow-up, the infarct region (determined by left ventriculography) had decreased significantly within the cell therapy group (from 30Ϯ13 to 12Ϯ7%, Pϭ0.005) and was also significantly smaller compared with the standard therapy group (Pϭ0.04). Likewise, infarction wall movement velocity increased significantly only in the cell therapy group (from 2.0Ϯ1.1 to 4.0Ϯ2.6 cm/s, Pϭ0.028). Further cardiac examinations (dobutamine stress echocardiography, radionuclide ventriculography, and catheterization of the right heart) were performed for the cell therapy group and showed significant improvement in stroke volume index, left ventricular end-systolic volume and contractility (ratio of systolic pressure and end-systolic volume), and myocardial perfusion of the infarct region. Conclusions-These results demonstrate for the first time that selective intracoronary transplantation of autologous, mononuclear BMCs is safe and seems to be effective under clinical conditions. The marked therapeutic effect may be attributed to BMC-associated myocardial regeneration and neovascularization.
Multifunctional 3D nanocomposite scaffolds with the ability for loading and sustained delivery of an antimicrobial agent, to eliminate and prevent bone infection and at the same time to contribute to bone regeneration process without cytotoxic effects on the surrounding tissue has been proposed. These 3D scaffolds exhibit a sustained levofloxacin delivery at physiological pH (pH 7.4), which increasing notably when pH decreases to characteristic values of bone infection process (pH 6.7 and pH 5.5). In vitro competitive assays between preosteoblastic and bacteria onto the 3D scaffold surface demonstrated an adequate osteoblast colonization in entire scaffold surface together with the ability to eliminate bacteria contamination.
These results for the first time demonstrate that selective intracoronary transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after transmural infarction. The therapeutic effects may be ascribed to stem cell-associated myocardial regeneration and neovascularisation.
Hintergrund: Das regenerative Potential humaner autologer adulter Stammzellen auf die Kardiomyogenese und Angiogenese nach Herzinfarkt könnte zur Infarktheilung beitragen, ist allerdings klinisch nicht untersucht. Vorgeschichte und Befund: Ein 46-jähriger Patient wurde 14 Stunden nach Einsetzen von linksthorakalen Schmerzen zur invasiven Diagnostik und Therapie zugewiesen. Die Herzkatheteruntersuchung zeigte einen Verschluss des Ramus interventricularis anterior der linken Kranzarterie, der durch Ballondilataion und Stentimplantation behandelt wurde. Wir haben erstmals die Indikation zur intrakoronaren Transplantation humaner autologer Stammzellen gestellt. Therapie und Ergebnis: Mononukleäre Knochenmarkzellen des Patienten wurden präpariert und 6 Tage nach transmuralem Vorderwandinfarkt selektiv über die rekanalisierte Infarktarterie in das Infarktgebiet während Niedrig-Druck-Ballondilatation (PTCA) transplantiert (1,2×10 7 Zellen, 10 ml). Vorher sowie 10 Wochen danach wurden die Auswirkungen der Stammzelltransplantation auf Ventrikelfunktion, Infarktgröße, Ventrikelgeometrie und Myokardperfusion unter Ruhe-und Belastungsbedingungen untersucht. Angewendet wurden: 201 Thallium-SPECT, mit »Bull's-eye«-Analyse, Dobutamin-Stressechokardiographie, Rechtsherzkatheter und Radionuklidventrikulographie 10 Wochen nach Stammzelltransplantation kam es zu einer deutlichen Verkleinerung der transmuralen Infarktnarbe mit Abnahme der Infarktgröße von 24,6% auf 15,7% der linksventrikulären Zirkumferenz, zu einer Zunahme von Auswurffraktion, Herzindex und Schlagindex zwischen 20-30%, zu einer Abnahme des enddiastolischen Volumens unter Belastung um 30% und zu einer quantitativ vergleichbaren Abnahme des linksventrikulären Füllungsdruckes (mittlerer Pulmonalkapillardruck, PC). Folgerung: Die Ergebnisse zeigen erstmals, dass die humane autologe, adulte Stammzelltransplantation mittels selektiver Herzkathetertechniken klinisch möglich und nutzbar ist und zur Regeneration der Narbe nach transmuralem Herzinfarkt führt. Ursächlich sind eine Stammzellen-assoziierte Kardiomyo-und Angioneogenese anzunehmen.Myocardial regeneration after intracoronary transplantation of human autologous stem cells following acute myocardial infarction Objektive: The regenerative potential of human autologous adult stem cells on myocardial regeneration and neovascularisation after myocardial infarction may contribute to healing of the infarction area. But no clinical application has previously been reported. We here describe for the first time the results of this method applied in a patient who had sustained an acute myocardial infarction. History and clinical findings: 14 hours after the onset of left precordial pain a 46-year-old man was admitted to our hospital for interventional diagnosis and treatment. Coronary angiography demonstrated occlusion of the anterior descending branch of the left coronary artery with transmural infarction. This was treated by percutaneous transluminal catheter angioplasty and stent placement. Therapy and results: Mononuclear ...
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