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 Citations (Scopus)

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 2012

Fingerprint

Bone Marrow Cells
Myocardium
Bone Marrow
Cell- and Tissue-Based Therapy
Cell Transplantation
Transcriptome
Oligonucleotide Array Sequence Analysis
Infarction
Genes
Cicatrix
Echocardiography
Heart Diseases
Suspensions
Electrocardiography
Therapeutics
Heart Failure
Myocardial Infarction
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology

Cite this

Lachtermacher, S., Esporcatte, B. L. B., da Silva de Azevedo Fortes, F., Rocha, N. N., Montalvão, F., Costa, P. C., ... 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

Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells. / Lachtermacher, Stephan; Esporcatte, Bruno L B; da Silva de Azevedo Fortes, Fábio; Rocha, Nazareth Novaes; Montalvão, Fabrício; Costa, Patricia C.; Belem, Luciano; Rabischoffisky, Arnaldo; Neto, Hugo C C Faria; Vasconcellos, Rita; Iacobas, Dumitru A.; Iacobas, Sanda; Spray, David C.; Thomas, Neil M.; Goldenberg, Regina C S; de Carvalho, Antonio C Campos.

In: Stem Cell Reviews and Reports, Vol. 8, No. 1, 03.2012, p. 251-261.

Research output: Contribution to journalArticle

Lachtermacher, S, Esporcatte, BLB, da Silva de Azevedo Fortes, F, Rocha, NN, Montalvão, F, Costa, PC, Belem, L, Rabischoffisky, A, Neto, HCCF, Vasconcellos, R, Iacobas, DA, Iacobas, S, Spray, DC, Thomas, NM, Goldenberg, RCS & de Carvalho, ACC 2012, 'Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells', Stem Cell Reviews and Reports, vol. 8, no. 1, pp. 251-261. https://doi.org/10.1007/s12015-011-9282-2
Lachtermacher S, Esporcatte BLB, da Silva de Azevedo Fortes F, Rocha NN, Montalvão F, Costa PC et al. Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells. Stem Cell Reviews and Reports. 2012 Mar;8(1):251-261. https://doi.org/10.1007/s12015-011-9282-2
Lachtermacher, Stephan ; Esporcatte, Bruno L B ; da Silva de Azevedo Fortes, Fábio ; Rocha, Nazareth Novaes ; Montalvão, Fabrício ; Costa, Patricia C. ; Belem, Luciano ; Rabischoffisky, Arnaldo ; Neto, Hugo C C Faria ; Vasconcellos, Rita ; Iacobas, Dumitru A. ; Iacobas, Sanda ; Spray, David C. ; Thomas, Neil M. ; Goldenberg, Regina C S ; de Carvalho, Antonio C Campos. / Functional and Transcriptomic Recovery of Infarcted Mouse Myocardium Treated with Bone Marrow Mononuclear Cells. In: Stem Cell Reviews and Reports. 2012 ; Vol. 8, No. 1. pp. 251-261.
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