TY - JOUR
T1 - Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells
AU - Lachtermacher, Stephan
AU - Esporcatte, Bruno L.B.
AU - da Silva de Azevedo Fortes, Fábio
AU - Rocha, Nazareth Novaes
AU - Montalvão, Fabrício
AU - Costa, Patricia C.
AU - Belem, Luciano
AU - Rabischoffisky, Arnaldo
AU - Neto, Hugo C.C.Faria
AU - Vasconcellos, Rita
AU - Iacobas, Dumitru A.
AU - Iacobas, Sanda
AU - Spray, David C.
AU - Thomas, Neil M.
AU - Goldenberg, Regina C.S.
AU - de Carvalho, Antonio C.Campos
N1 - Funding Information:
Male and female C57BL/6 mice, aged from 8–10 weeks (20.5–25.5 g) were obtained from the Animal Facility of the Federal University of Rio de Janeiro. Mice were housed at controlled temperature (23°C) with a 12:12 h light–dark cycle and received standard mouse chow and water ad libitum. This investigation conformed to the Guide for the Care and Use of Laboratory Animals (Institute of Laboratory Animal Research, Commission on Life Science, National Research Council, USA) and was approved by the Institutional Animal Committee at the Federal University of Rio de Janeiro.
PY - 2012/3
Y1 - 2012/3
N2 - 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.
AB - 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.
KW - Cardiac function
KW - Heart failure
KW - Immune-inflammatory response
KW - Microarray analysis
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U2 - 10.1007/s12015-011-9282-2
DO - 10.1007/s12015-011-9282-2
M3 - Article
C2 - 21671060
AN - SCOPUS:84857649068
SN - 1550-8943
VL - 8
SP - 251
EP - 261
JO - Stem Cell Reviews and Reports
JF - Stem Cell Reviews and Reports
IS - 1
ER -