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.

journal_name

Stem Cell Rev Rep

authors

Lachtermacher S,Esporcatte BL,Fortes Fda S,Rocha NN,Montalvão F,Costa PC,Belem L,Rabischoffisky A,Faria Neto HC,Vasconcellos R,Iacobas DA,Iacobas S,Spray DC,Thomas NM,Goldenberg RC,de Carvalho AC

doi

10.1007/s12015-011-9282-2

subject

Has Abstract

pub_date

2012-03-01 00:00:00

pages

251-61

issue

1

eissn

2629-3269

issn

2629-3277

journal_volume

8

pub_type

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