Open AccessTransplantation of expanded bone marrow‐derived very small embryonic‐like stem cells (VSEL‐SCs) improves left ventricular function and remodelling after myocardial infarction
Author(s) -
ZubaSurma Ewa K.,
Guo Yiru,
Taher Hisham,
Sanganalmath Santosh K.,
Hunt Greg,
Vincent Robert J.,
Kucia Magda,
AbdelLatif Ahmed,
Tang XianLiang,
Ratajczak Mariusz Z.,
Dawn Buddhadeb,
Bolli Roberto
Publication year - 2011
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2010.01126.x
Subject(s) - transplantation , bone marrow , stem cell , medicine , cardiology , embryonic stem cell , ventricular remodeling , bone marrow stem cell , myocardial infarction , biology , microbiology and biotechnology , biochemistry , gene
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 × 10 6 ) 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 × 10 5 enhanced green fluorescent protein (EGFP)‐labelled expanded untreated VSEL‐SCs (group II, n = 7), or 1 × 10 5 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.