Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction

Ewa K. Zuba-Surma, Yiru Guo, Hisham Taher, Santosh K. Sanganalmath, Greg Hunt, Robert J. Vincent, Magda Kucia, Ahmed Abdel-Latif, Xian Liang Tang, Mariusz Z. Ratajczak, Buddhadeb Dawn, Roberto Bolli

Research output: Contribution to journalArticle

Abstract

Adult bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) exhibit a Sca-1+/Lin-/CD45- phenotype and can differentiate into various cell types, including cardiomyocytes and endothelial cells. We have previously reported that transplantation of a small number (1 × 106) of freshly isolated, non-expanded VSEL-SCs into infarcted mouse hearts resulted in improved left ventricular (LV) function and anatomy. Clinical translation, however, will require large numbers of cells. Because the frequency of VSEL-SCs in the marrow is very low, we examined whether VSEL-SCs can be expanded in culture without loss of therapeutic efficacy. Mice underwent a 30 min. coronary occlusion followed by reperfusion and, 48 hrs later, received an intramyocardial injection of vehicle (group I, n= 11), 1 × 105 enhanced green fluorescent protein (EGFP)-labelled expanded untreated VSEL-SCs (group II, n= 7), or 1 × 105 EGFP-labelled expanded VSEL-SCs pre-incubated in a cardiogenic medium (group III, n= 8). At 35 days after myocardial infarction (MI), mice treated with pre-incubated VSEL-SCs exhibited better global and regional LV systolic function and less LV hypertrophy compared with vehicle-treated controls. In contrast, transplantation of expanded but untreated VSEL-SCs did not produce appreciable reparative benefits. Scattered EGFP+ cells expressing α-sarcomeric actin, platelet endothelial cell adhesion molecule (PECAM)-1, or von Willebrand factor were present in VSEL-SC-treated mice, but their numbers were very small. No tumour formation was observed. We conclude that VSEL-SCs expanded in culture retain the ability to alleviate LV dysfunction and remodelling after a reperfused MI provided that they are exposed to a combination of cardiomyogenic growth factors and cytokines prior to transplantation. Counter intuitively, the mechanism whereby such pre-incubation confers therapeutic efficacy does not involve differentiation into new cardiac cells. These results support the potential therapeutic utility of VSEL-SCs for cardiac repair.

Original languageEnglish (US)
Pages (from-to)1319-1328
Number of pages10
JournalJournal of Cellular and Molecular Medicine
Volume15
Issue number6
DOIs
StatePublished - Jun 2011
Externally publishedYes

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Ventricular Remodeling
Embryonic Stem Cells
Bone Marrow Transplantation
Left Ventricular Function
Myocardial Infarction
Transplantation
Bone Marrow
CD31 Antigens
Coronary Occlusion
von Willebrand Factor
Left Ventricular Dysfunction
Left Ventricular Hypertrophy
Cardiac Myocytes
Reperfusion
Actins
Anatomy
Intercellular Signaling Peptides and Proteins
Therapeutics
Endothelial Cells
Cell Count

Keywords

  • Bone marrow
  • Left ventricular function
  • Myocardial infarction
  • Myocardial repair
  • Remodelling
  • Stem cell
  • VSEL-SCs

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction. / Zuba-Surma, Ewa K.; Guo, Yiru; Taher, Hisham; Sanganalmath, Santosh K.; Hunt, Greg; Vincent, Robert J.; Kucia, Magda; Abdel-Latif, Ahmed; Tang, Xian Liang; Ratajczak, Mariusz Z.; Dawn, Buddhadeb; Bolli, Roberto.

In: Journal of Cellular and Molecular Medicine, Vol. 15, No. 6, 06.2011, p. 1319-1328.

Research output: Contribution to journalArticle

Zuba-Surma, EK, Guo, Y, Taher, H, Sanganalmath, SK, Hunt, G, Vincent, RJ, Kucia, M, Abdel-Latif, A, Tang, XL, Ratajczak, MZ, Dawn, B & Bolli, R 2011, 'Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction', Journal of Cellular and Molecular Medicine, vol. 15, no. 6, pp. 1319-1328. https://doi.org/10.1111/j.1582-4934.2010.01126.x
Zuba-Surma, Ewa K. ; Guo, Yiru ; Taher, Hisham ; Sanganalmath, Santosh K. ; Hunt, Greg ; Vincent, Robert J. ; Kucia, Magda ; Abdel-Latif, Ahmed ; Tang, Xian Liang ; Ratajczak, Mariusz Z. ; Dawn, Buddhadeb ; Bolli, Roberto. / Transplantation of expanded bone marrow-derived very small embryonic-like stem cells (VSEL-SCs) improves left ventricular function and remodelling after myocardial infarction. In: Journal of Cellular and Molecular Medicine. 2011 ; Vol. 15, No. 6. pp. 1319-1328.
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AU - Taher, Hisham

AU - Sanganalmath, Santosh K.

AU - Hunt, Greg

AU - Vincent, Robert J.

AU - Kucia, Magda

AU - Abdel-Latif, Ahmed

AU - Tang, Xian Liang

AU - Ratajczak, Mariusz Z.

AU - Dawn, Buddhadeb

AU - Bolli, Roberto

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