4.5 Article

Time-Dependent Migration of Systemically Delivered Bone Marrow Mesenchymal Stem Cells to the Infarcted Heart

Journal

CELL TRANSPLANTATION
Volume 19, Issue 2, Pages 219-230

Publisher

SAGE PUBLICATIONS INC
DOI: 10.3727/096368909X479677

Keywords

Myocardial infarction; Mesenchymal stem cells; Homing; Body distribution

Funding

  1. CNPq (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico)
  2. CAPES (Coordenacao de Aperfiecoamento de Pessoal de Nivel Superior)
  3. FAPEMIG (Fondacao de Amparo a Pesquisa do Estado de Minas Gerais)

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In this study the time course of homing and the body distribution of systemically delivered bone marrow mesenchymal stem cells (BM-MSCs) after myocardial infarction (MI) were evaluated BM-MSCs were isolated from Wistar rats, expanded in vitro, and their phenotypical characterization was performed by flow cytometer Rats were randomly divided into three groups control, sham MI, and MI BM-MSCs (5 x 106) were labeled with Tc-99m-HMPAO and injected through the tail vein 7 days after MI Gamma camera imaging was performed at 5, 15, 30, and 60 mm after cell inoculation Due to the Tc-99m short half-life, cell migration and location were also evaluated in heart sections using DAPI-labeled cells 7 days after transplantation Phenotypical characterization showed that BM-MSCs were CD90(+), CD73(+), CD54(+), and CD45(-) Five minutes after Tc-99m-HMPAO-labeled cell injection. they were detected in various tissues The cells migrated mainly to the lungs (approximately 70%) and. in small amounts, to the heart, kidneys, spleen, and bladder The number of cells in the heart and lungs decreased after 60 min MI markedly Increased the amount of cells in the heart. but not in the lungs. during the period of observation (4.55 +/- 0 32 vs 6 34 +/- 0 67% of uptake in infarcted hearts) No significant differences were observed between control and sham groups Additionally, 7 days after DAPI-labeled cells injection, they were still detected in the heart but only in infarcted areas. These results suggest that the migration of systemically delivered BM-MSCs to the heart is time dependent and MI specifically increases BM-MSCs homing to injured hearts However, the systemic delivery is limited by cell entrapment in the lungs

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