title: Functional and transcriptomic recovery of infarcted mouse myocardium treated with bone marrow mononuclear cells.
abstract: 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.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Bloco G, Ilha do Fundão 21949-900, Rio de Janeiro, RJ, Brazil.
authors.forename: Stephan
authors.initials: S
authors.lastname: Lachtermacher
authors.forename: Bruno L B
authors.initials: BL
authors.lastname: Esporcatte
authors.forename: Fábio da Silva de Azevedo
authors.initials: Fda S
authors.lastname: Fortes
authors.forename: Nazareth Novaes
authors.initials: NN
authors.lastname: Rocha
authors.forename: Fabrício
authors.initials: F
authors.lastname: Montalvão
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Costa
authors.forename: Luciano
authors.initials: L
authors.lastname: Belem
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Rabischoffisky
authors.forename: Hugo C C
authors.initials: HC
authors.lastname: Faria Neto
authors.forename: Rita
authors.initials: R
authors.lastname: Vasconcellos
authors.forename: Dumitru A
authors.initials: DA
authors.lastname: Iacobas
authors.forename: Sanda
authors.initials: S
authors.lastname: Iacobas
authors.forename: David C
authors.initials: DC
authors.lastname: Spray
authors.forename: Neil M
authors.initials: NM
authors.lastname: Thomas
authors.forename: Regina C S
authors.initials: RC
authors.lastname: Goldenberg
authors.forename: Antonio C Campos
authors.initials: AC
authors.lastname: de Carvalho
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D018836:Inflammation Mediators / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption; D005082:Physical Exertion; D059467:Transcriptome; D020257:Ventricular Remodeling
chemical_list: D018836:Inflammation Mediators