Endometrial stem cell differentiation into smooth muscle cell: a novel approach for bladder tissue engineering in women

2013 ◽  
Vol 112 (6) ◽  
pp. 854-863 ◽  
Author(s):  
Alireza Shoae-Hassani ◽  
Shiva Sharif ◽  
Alexander M. Seifalian ◽  
Seyed Abdolreza Mortazavi-Tabatabaei ◽  
Sassan Rezaie ◽  
...  
2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Adam J Schuldt ◽  
Rommel C Morales ◽  
Zheng Wang ◽  
Vera P Shively ◽  
Melina R Kibbe

Introduction: Treatment outcomes for severe atherosclerosis are limited by neointimal hyperplasia and restenosis. Nitric oxide (NO) is a potent inhibitor of neointimal hyperplasia, but its effects on vascular progenitor cells (VPC) in this process are unknown. Stem cell antigen-1-positive (Sca-1 + ) VPC can differentiate into both vascular smooth muscle cells (VSMC) and endothelial cells, which potentially contribute to or prevent the development of neointimal hyperplasia and restenosis, respectively. We hypothesize that NO favors differentiation of Sca-1 + VPC into endothelial cells rather than VSMC, thereby limiting the development of neointimal hyperplasia. Methods: Aortas from WT C57BL/6 male mice were digested and analyzed by FACS for Sca-1 and hematopoietic lineage (Lin) markers CD3e, CD11b, CD45, Ly-76, and Ly-6C/G. Aortic Sca-1 + cells were enriched by magnetic activated cell sorting and cultured at passage 2-3 for 72 hours in stem cell media or smooth muscle cell differentiation media containing PDGF-BB, with the NO donor DETA/NO (0-100 μM). CD31 + cells were assessed by FACS. Results: Sca-1 + /Lin - cells comprised 9.0±1.6% of total aortic cells (n=4 replicates, 8 mice each). Aortic Sca-1 + cells in stem cell media showed an increase in CD31 + cells from 5.0±1.9% in controls to 6.8±2.3% and 11.2±1.7% with 50 and 100 μM DETA/NO, respectively (p<0.05). Aortic Sca-1 + cells in smooth muscle cell differentiation media showed an increase in CD31 + cells from 4.3±1.2% in controls to 5.0±1.3% and 7.2 ±1.9% with 50 and 100 μM DETA/NO, respectively (p<0.05). Conclusion: The arterial wall contains Sca-1 + VPC with the ability to differentiate into multiple lineages. In support of our hypothesis, exposure to NO in vitro increased differentiation of Sca-1 + VPC to endothelial-like cells, even when the VSMC differentiation stimulus of PDGF-BB is present. This shift toward endothelial differentiation with NO may act to decrease neointimal hyperplasia in vivo .


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