| Murine c‐kit+ cardiac cells were isolated and enriched by magnetic activated cell
sorting technique. c‐kit+ cells viability and colony‐forming activity were evaluated
by MTT and clonogenic assay. c‐kit+ cells were exposed to endothelial, pericyte, and
cardiomyocyte induction media containing 30mM glucose for 7 days. We monitored
the level of endothelial (VE‐cadherin, CD31, and vWF), pericyte (NG2, α‐SMA, and
PDGFR‐β), and cardiomyocyte markers (cTnT) using flow cytometry, real‐time
Polymerase Chain Reaction (PCR), and Enzyme‐Linked Immunosorbent Assay (ELISA)
analyses. Ultrastructural changes were studied by transmission electron microscopy
(TEM) in cells treated with 5‐Azacytidine and 30mM glucose. Matrigel plug assay
was performed to determine the angio/cardiogenic property of c‐kit+ cells in a diabetic
mouse model. Glucose of 30mM decreased c‐kit+ cells viability and
clonogenicity (P < 0.05). The transdifferentiation capacity of c‐kit+ cells into the
endothelial lineage, pericytes, and cardiomyocytes were reduced through the inhibition
of related genes (P < 0.05). TEM analysis revealed cardiomyocyte differentiation
rate in c‐kit+ cells coincided with an increased intracellular lipid accumulation and
reduced number of mitochondria. Similar to in vitro condition, the angiogenic capacity
of c‐kit+ cells was aborted in vivo indicated by reduced NG2, α‐SMA, CD31, and vWF
levels. High glucose condition reduces the angio/cardiogenic capacity of cardiac c‐kit+
cells in vitro and in vivo.
Significance of the study High glucose condition seen in diabetes mellitus could
affect the regenerative potential of cardiac tissue. The current experiment showed
that the exposure of murine cardiac progenitor cells (CD117+ cells) to condition containing
30mM glucose could decrease the differentiation properties into endothelial
cells, pericytes, and mature cardiomyocytes in vitro and in vivo. Our finding confirmed
that the angiogenic/cardiogenic potential cardiac progenitor cells decrease under
treatment with high glucose content as seen in the diabetic condition. |