Homing of peripherally injected bone marrow cells in the rat after experimental myocardial injury

Michele M. Ciulla, Lorenza Lazzari, Raffaella Pacchiana, Arturo Esposito, Silvano Bosari, Stefano Ferrero, Umberto Gianelli, Roberta Paliotti, Giuseppe Busca, Alessandra Giorgetti, Fabio Magrini, Paolo Rebulla

Research output: Contribution to journalArticle

Abstract

Background and Objectives. Significant progress has been achieved during the past 10 years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair are performed by direct intramyocardial injection of cells of different origin. Since this approach requires a surgical intervention, in this study we investigated the feasibility of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by assessing the fate of peripherally injected, purified, labeled cells in cryodamaged hearts. Design and Methods. Ten donor and ten recipient inbred isogenic adult (4 weeks old) Fisher rats were used as models to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by placing a frozen metal probe on the anterior left ventricular wall for 15 seconds (freeze-thaw injury technique). BMMNCs were purified and labeled with a red fluorescent cell dye. Seven days after the injury about 15-25×106 cells were infused through the femoral vein of recipient rats. Seven days after the infusion, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells. Results. Labeled cells were found only in the injured area of the heart and not in the normal tissue; a limited number of cells were also identified in the spleen of all the animals. Most of the labeled cells in the infarcted area were Thy-1+ and some were CD34+. Interpretation and Conclusions. Our data suggest that peripherally injected BMMNCs can traffic through the circulation to the site of damage; we hypothesize that tissue injury leads to the priming of a cytokine cascade acting as chemoattractant for the infused cells.

Original languageEnglish
Pages (from-to)614-621
Number of pages8
JournalHaematologica
Volume88
Issue number6
Publication statusPublished - Jun 1 2003

Fingerprint

Bone Marrow Cells
Wounds and Injuries
Spleen
Femoral Vein
Ventricular Function
Autologous Transplantation
Chemotactic Factors
Cell Transplantation
Feasibility Studies
Fluorescent Dyes
Thymus Gland
Cell Count
Metals
Myocardial Infarction
Cytokines
Kidney
Lung
Injections
Liver
Research

Keywords

  • Bone marrow
  • Cryoinduced myocardial damage
  • Systemic injection

ASJC Scopus subject areas

  • Hematology

Cite this

Homing of peripherally injected bone marrow cells in the rat after experimental myocardial injury. / Ciulla, Michele M.; Lazzari, Lorenza; Pacchiana, Raffaella; Esposito, Arturo; Bosari, Silvano; Ferrero, Stefano; Gianelli, Umberto; Paliotti, Roberta; Busca, Giuseppe; Giorgetti, Alessandra; Magrini, Fabio; Rebulla, Paolo.

In: Haematologica, Vol. 88, No. 6, 01.06.2003, p. 614-621.

Research output: Contribution to journalArticle

Ciulla, MM, Lazzari, L, Pacchiana, R, Esposito, A, Bosari, S, Ferrero, S, Gianelli, U, Paliotti, R, Busca, G, Giorgetti, A, Magrini, F & Rebulla, P 2003, 'Homing of peripherally injected bone marrow cells in the rat after experimental myocardial injury', Haematologica, vol. 88, no. 6, pp. 614-621.
Ciulla, Michele M. ; Lazzari, Lorenza ; Pacchiana, Raffaella ; Esposito, Arturo ; Bosari, Silvano ; Ferrero, Stefano ; Gianelli, Umberto ; Paliotti, Roberta ; Busca, Giuseppe ; Giorgetti, Alessandra ; Magrini, Fabio ; Rebulla, Paolo. / Homing of peripherally injected bone marrow cells in the rat after experimental myocardial injury. In: Haematologica. 2003 ; Vol. 88, No. 6. pp. 614-621.
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AU - Lazzari, Lorenza

AU - Pacchiana, Raffaella

AU - Esposito, Arturo

AU - Bosari, Silvano

AU - Ferrero, Stefano

AU - Gianelli, Umberto

AU - Paliotti, Roberta

AU - Busca, Giuseppe

AU - Giorgetti, Alessandra

AU - Magrini, Fabio

AU - Rebulla, Paolo

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N2 - Background and Objectives. Significant progress has been achieved during the past 10 years in cell transplantation and recent research has focused on the possibility of improving ventricular function after myocardial infarction. Most studies in the field of cardiac tissue repair are performed by direct intramyocardial injection of cells of different origin. Since this approach requires a surgical intervention, in this study we investigated the feasibility of non-invasive administration of bone marrow mononuclear cells (BMMNCs) by assessing the fate of peripherally injected, purified, labeled cells in cryodamaged hearts. Design and Methods. Ten donor and ten recipient inbred isogenic adult (4 weeks old) Fisher rats were used as models to mimic autologous transplantation. Myocardial damage was obtained in recipient rats by placing a frozen metal probe on the anterior left ventricular wall for 15 seconds (freeze-thaw injury technique). BMMNCs were purified and labeled with a red fluorescent cell dye. Seven days after the injury about 15-25×106 cells were infused through the femoral vein of recipient rats. Seven days after the infusion, the heart, lungs, liver, kidneys, spleen and thymus were harvested to track transplanted cells. Results. Labeled cells were found only in the injured area of the heart and not in the normal tissue; a limited number of cells were also identified in the spleen of all the animals. Most of the labeled cells in the infarcted area were Thy-1+ and some were CD34+. Interpretation and Conclusions. Our data suggest that peripherally injected BMMNCs can traffic through the circulation to the site of damage; we hypothesize that tissue injury leads to the priming of a cytokine cascade acting as chemoattractant for the infused cells.

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KW - Cryoinduced myocardial damage

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