Functional and transcriptomic recovery of infarcted mouse myocardium treated with bone marrow mononuclear cells.

Although bone marrow-derived mononuclear cells (BMNC) have been extensively used in cell therapy for cardiac diseases, little mechanistic information is available to support reports of their efficacy. To address this shortcoming, we compared structural and functional recovery and associated global gene expression profiles in post-ischaemic myocardium treated with BMNC transplantation. BMNC suspensions were injected into cardiac scar tissue 10 days after experimental myocardial infarction. Six weeks later, mice undergoing BMNC therapy were found to have normalized antibody repertoire and improved cardiac performance measured by ECG, treadmill exercise time and echocardiography. After functional testing, gene expression profiles in cardiac tissue were evaluated using high-density oligonucleotide arrays. Expression of more than 18% of the 11981 quantified unigenes was significantly altered in the infarcted hearts. BMNC therapy restored expression of 2099 (96.2%) of the genes that were altered by infarction but led to altered expression of 286 other genes, considered to be a side effect of the treatment. Transcriptional therapeutic efficacy, a metric calculated using a formula that incorporates both recovery and side effect of treatment, was 73%. In conclusion, our results confirm a beneficial role for bone marrow-derived cell therapy and provide new information on molecular mechanisms operating after BMNC transplantation on post ischemic heart failure in mice.

Autologous bone-marrow mononuclear cell transplantation after acute myocardial infarction: comparison of two delivery techniques.

The objective of this study was to investigate safety and feasibility of autologous bone marrow mononuclear cells (BMMNC) transplantation in ST elevation myocardial infarction (STEMI), comparing anterograde intracoronary artery (ICA) delivery with retrograde intracoronary vein (ICV) approach. An open labeled, randomized controlled trial of 30 patients admitted with STEMI was used. Patients were enrolled if they 1) were successfully reperfused within 24 h from symptoms onset and 2) had infarct size larger than 10% of the left ventricle (LV). One hundred million BMMNC were injected in the infarct-related artery (intra-arterial group) or vein (intravenous group), 1% of which was labeled with Tc(99m)-hexamethylpropylenamineoxime. Cell distribution was evaluated 4 and 24 h after injection. Baseline MRI was performed in order to evaluate microbstruction pattern. Baseline radionuclide ventriculography was performed before cell transfer and after 3 and 6 months. All the treated patients were submitted to repeat coronary angiography after 3 months. Thirty patients (57 +/- 11 years, 70% males) were randomly assigned to ICA (n = 14), ICV (n = 10), or control (n = 6) groups. No serious adverse events related to the procedure were observed. Early and late retention of radiolabeled cells was higher in the ICA than in the ICV group, independently of microcirculation obstruction. An increase of EF was observed in the ICA group (p = 0.02) compared to baseline. Injection procedures through anterograde and retrograde approaches seem to be feasible and safe. BMMNC retention by damaged heart tissue was apparently higher when the anterograde approach was used. Further studies are required to confirm these initial data.

Avaliação da função diastólica após o transplante autólogo, intracoronário, de células mononucleares da medula óssea em pacientes submetidos à angioplastia primária / Left ventricle diastolic function after intracoronary autologous bone marrow mononuclear cells transplantation in patients treated primary angioplasty

Objetivo:Avaliar o impacto do transplante autólogo de células mononucleares da medula óssea(TACMMO) sobre a função diastólica(FD) do ventrículo esquerdo, através do ecocardiograma(ECO) COM Doppler Tecidual(DT). Métodos: Estudo randomizado e aberto. Foram incluídos 9 pacientes(7 homens), admitidos no Hospital Pró-Cardíaco com IAM com supradesnivelamento do segmento ST e submetidos a angioplastia primária coronariana com sucesso. Estavam entre o 3° e 5° dias pós-infarto, com disfunção segmentar no ECO e defeito fixo de perfusão maior que 10 por cento na área relacionada ao infarto na cintigrafia de repouso. Foram acompanhados por 3 meses e distribuídos aleatoriamente em 2 grupos: grupo tratado com TACMMO (GT; n igual 6) e grupo controle(GC, n igual 3). O ECO foi arquivado digitalmente e analisado de forma "cega". Foi estudado o fluxo diastólico mitral(FDM), incluindo-se os picosE, A e relação E/A. Ao DT avaliaram-se os picos E' e A' do anel mitral(AM) lateral(E'lat e A'lat) e septal(E's e A's), além das relações E'lat/A'lat, E's/A's entre os picos E e E'lat(E/E'). Resultados: No GT, normalizou-se o FDM em 2 pacientes. No GC piorou o FDM em 1 paciente, sem melhora nos outros 2. Ao DT, ocorreu normalização da FD em 3 pacientes no AM septal, sem melhora no GC. O E'lat diminuiu no GC e aumentou no GT. A E'lat não mudou no GC e aumentou no GT. A E/E' aumentou no GC e diminuiu no GT. Conclusões: Nos pacientes estudados, a FD analisada pelo FDM e pelo DT apresentou melhor evolução no grupo com TACMMO