Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells

Stephan Lachtermacher, Bruno L.B. Esporcatte, Fábio da Silva de Azevedo Fortes, Nazareth Novaes Rocha, Fabrício Montalvão, Patricia C. Costa, Luciano Belem, Arnaldo Rabischoffisky, Hugo C.C.Faria Neto, Rita Vasconcellos, Dumitru A. Iacobas, Sanda Iacobas, David C. Spray, Neil M. Thomas, Regina C.S. Goldenberg, Antonio C.Campos de Carvalho

Research output: Contribution to journalArticle

12 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalStem Cell Reviews and Reports
Volume8
Issue number1
DOIs
StatePublished - Mar 1 2012

Keywords

  • Cardiac function
  • Heart failure
  • Immune-inflammatory response
  • Microarray analysis

ASJC Scopus subject areas

  • Cell Biology
  • Cancer Research

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    Lachtermacher, S., Esporcatte, B. L. B., da Silva de Azevedo Fortes, F., Rocha, N. N., Montalvão, F., Costa, P. C., Belem, L., Rabischoffisky, A., Neto, H. C. C. F., Vasconcellos, R., Iacobas, D. A., Iacobas, S., Spray, D. C., Thomas, N. M., Goldenberg, R. C. S., & de Carvalho, A. C. C. (2012). Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells. Stem Cell Reviews and Reports, 8(1), 251-261. https://doi.org/10.1007/s12015-011-9282-2