Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction

Buddhadeb Dawn, Sumit Tiwari, Magdalena J. Kucia, Ewa K. Zuba-Surma, Yiru Guo, Santosh K. Sanganalmath, Ahmed Abdel-Latif, Greg Hunt, Robert J. Vincent, Hisham Taher, Nathan J. Reed, Mariusz Z. Ratajczak, Roberto Bolli

Research output: Contribution to journalArticlepeer-review

Abstract

Adult bone marrow (BM) contains Sca-1+/Lin-/CD45-very small embryonic-like stem cells (VSELs) that express markers of several lineages, including cardiac markers, and differentiate into cardiomyocytes in vitro. We examined whether BM-derived VSELs promote myocardial repair after a reperfused myocardial infarction (MI). Mice underwent a 30-minute coronary occlusion followed by reperfusion and received intramyocardial injection of vehicle (n = 11), 1 × 105 Sca-1+/Lin-/CD45+ enhanced green fluorescent protein (EGFP)-labeled hematopoietic stem cells (n = 13 [cell control group]), or 1 × 104 Sca-1+/Lin-/CD45- EGFP-labeled cells (n = 14 [VSEL-treated group]) at 48 hours after MI. At 35 days after MI, VSEL-treated mice exhibited improved global and regional left ventricular (LV) systolic function (echocardiography) and attenuated myocyte hypertrophy in surviving tissue (histology and echocardiography) compared with vehicle-treated controls. In contrast, transplantation of Sca-1+/Lin-/CD45+ cells failed to confer any functional or structural benefits. Scattered EGFP+ myocytes and capillaries were present in the infarct region in VSEL-treated mice, but their numbers were very small. These results indicate that transplantation of a relatively small number of CD45+ VSELs is sufficient to improve LV function and alleviate myocyte hypertrophy after MI, supporting the potential therapeutic utility of these cells for cardiac repair.

Original languageEnglish (US)
Pages (from-to)1646-1655
Number of pages10
JournalStem Cells
Volume26
Issue number6
DOIs
StatePublished - Jun 2008
Externally publishedYes

Keywords

  • Bone marrow
  • Left ventricular function
  • Myocardial infarction
  • Myocardial regeneration
  • Stem cell
  • Very small embryonic-like stem cell

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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