Sox2 transduction enhances cardiovascular repair capacity of blood-derived mesoangioblasts.
Circ Res
; 106(7): 1290-302, 2010 Apr 16.
Article
in En
| MEDLINE
| ID: mdl-20185800
ABSTRACT
RATIONALE Complementation of pluripotency genes may improve adult stem cell functions. OBJECTIVES:
Here we show that clonally expandable, telomerase expressing progenitor cells can be isolated from peripheral blood of children. The surface marker profile of the clonally expanded cells is distinct from hematopoietic or mesenchymal stromal cells, and resembles that of embryonic multipotent mesoangioblasts. Cell numbers and proliferative capacity correlated with donor age. Isolated circulating mesoangioblasts (cMABs) express the pluripotency markers Klf4, c-Myc, as well as low levels of Oct3/4, but lack Sox2. Therefore, we tested whether overexpression of Sox2 enhances pluripotency and facilitates differentiation of cMABs in cardiovascular lineages. METHODS ANDRESULTS:
Lentiviral transduction of Sox2 (Sox-MABs) enhanced the capacity of cMABs to differentiate into endothelial cells and cardiomyocytes in vitro. Furthermore, the number of smooth muscle actin positive cells was higher in Sox-MABs. In addition, pluripotency of Sox-MABs was shown by demonstrating the generation of endodermal and ectodermal progenies. To test whether Sox-MABs may exhibit improved therapeutic potential, we injected Sox-MABs into nude mice after acute myocardial infarction. Four weeks after cell therapy with Sox-MABs, cardiac function was significantly improved compared to mice treated with control cMABs. Furthermore, cell therapy with Sox-MABs resulted in increased number of differentiated cardiomyocytes, endothelial cells, and smooth muscle cells in vivo.CONCLUSIONS:
The complementation of Sox2 in Oct3/4-, Klf4-, and c-Myc-expressing cMABs enhanced the differentiation into all 3 cardiovascular lineages and improved the functional recovery after acute myocardial infarction.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Regeneration
/
Leukocytes, Mononuclear
/
Muscle, Skeletal
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Pluripotent Stem Cells
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Peripheral Blood Stem Cell Transplantation
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SOXB1 Transcription Factors
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Ischemia
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Myocardial Infarction
Type of study:
Prognostic_studies
Limits:
Aged80
Language:
En
Journal:
Circ Res
Year:
2010
Document type:
Article
Affiliation country:
Germany