Abstract 13831: Atrial and Ventricular Cardiac Stem Cells From the Same Heart Exhibit Differential Functional Characteristics for Cardiac Regeneration but Are Superior to the Endothelial Progenitor Cells From the Same Patient
Introduction: Deciding the best cell type for cardiac regeneration remains a challenge, however, no studies have directly compared the functional efficacy of cardiac stem cells (CSCs) with extra- cardiac SCs isolated from the same patient.
Objective: To compare the functional characteristics of endothelial progenitor cells (EPCs), right atrial (RAA) CSCs and left ventricular (LV) CSCs isolated from the same patients.
Methods and Results: Flow-cytometry analysis of CSCs (n=12 patients) revealed higher expression of CD90 (involved in cell adhesion and migration) in RAA CSCs (CD90 & CD105 ++ve cells: 71±15% in RAA vs. 47±27% in LV, P<0.05). However, scratch assay showed superior wound closure in LV CSCs (80±10% in LV vs. 60±5% in RAA, P<0.05) suggesting that LV CSCs have a better migration potential. Moreover, the expansion properties of RAA CSCs were better than LV CSCs in terms of higher cumulative population doublings in culture. To simulate in vivo ischemic environment, cells were subjected to hypoxia (1% O2) and serum starvation for 3 days. RAA and LV CSCs exhibited similar pattern of resistance to apoptotic cell death (evaluated as percentage of annexin +ve cells, n=5) and proliferation under hypoxia. Interestingly, EPCs exhibited highest resistance to apoptotic cell death, but they also showed the lowest proliferation under hypoxia (P<0.05). Secretion of paracrine and pro-angiogenic factors have been thought to be most important mechanisms behind cardiac regeneration. Therefore, to compare the paracrine angiogenic and wound healing potential, HUVECs were cultured in culture supernatant (CS) from all the 3 cell types. RAA-CS showed the highest increase in tube formation capacity (P<0.05, n=6), while the scratch assay showed comparable wound closure with both LV and RAA CS (67.56 ± 7.36% and 70.02 ± 5.70%, n=5), but was lowest in EPC CS (54±7%). The secretion of the angiogenic growth factor VEGF-A (n=5) was lowest in EPCs (0.36± 0.20 ng/mL) and comparable between RAA (3.44±1.94 ng/mL) and LV CSCs (4.33± 1.57 ng/mL).
Conclusion: Stem cells from different regions exhibit differential functional characteristics within the same patient. The selection of the best cell type should therefore be influenced by the nature of the injury and the type of effect desired.
Author Disclosures: P. Dixit: None. H. Donnelly: None. M. Edamatsu: None. I. Galvin: None. R. Bunton: None. R. Katare: None.
- © 2015 by American Heart Association, Inc.