scholarly journals Parity induces differentiation and reduces Wnt/Notch signaling ratio and proliferation potential of basal stem/progenitor cells isolated from mouse mammary epithelium

2013 ◽  
Vol 15 (2) ◽  
Author(s):  
Fabienne Meier-Abt ◽  
Emanuela Milani ◽  
Tim Roloff ◽  
Heike Brinkhaus ◽  
Stephan Duss ◽  
...  
2004 ◽  
Vol 165 (2) ◽  
pp. 695-705 ◽  
Author(s):  
Hippokratis Kiaris ◽  
Katerina Politi ◽  
Lisa M. Grimm ◽  
Matthias Szabolcs ◽  
Peter Fisher ◽  
...  

Blood ◽  
2011 ◽  
Vol 117 (23) ◽  
pp. 6083-6090 ◽  
Author(s):  
Ann Dahlberg ◽  
Colleen Delaney ◽  
Irwin D. Bernstein

AbstractDespite progress in our understanding of the growth factors that support the progressive maturation of the various cell lineages of the hematopoietic system, less is known about factors that govern the self-renewal of hematopoietic stem and progenitor cells (HSPCs), and our ability to expand human HSPC numbers ex vivo remains limited. Interest in stem cell expansion has been heightened by the increasing importance of HSCs in the treatment of both malignant and nonmalignant diseases, as well as their use in gene therapy. To date, most attempts to ex vivo expand HSPCs have used hematopoietic growth factors but have not achieved clinically relevant effects. More recent approaches, including our studies in which activation of the Notch signaling pathway has enabled a clinically relevant ex vivo expansion of HSPCs, have led to renewed interest in this arena. Here we briefly review early attempts at ex vivo expansion by cytokine stimulation followed by an examination of our studies investigating the role of Notch signaling in HSPC self-renewal. We will also review other recently developed approaches for ex vivo expansion, primarily focused on the more extensively studied cord blood–derived stem cell. Finally, we discuss some of the challenges still facing this field.


2011 ◽  
pp. P1-132-P1-132
Author(s):  
Lauren Rota ◽  
Deborah A Lazzarino ◽  
Sain Shushanov ◽  
Derek LeRoith ◽  
Teresa L Wood

2006 ◽  
Vol 120 (3) ◽  
pp. 493-499 ◽  
Author(s):  
Brian W. Booth ◽  
Chamelli Jhappan ◽  
Glenn Merlino ◽  
Gilbert H. Smith

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
David Q Trac ◽  
Chunhui Xu ◽  
Michael E. Davis

Congenital heart disease is rarely cured by surgery and can lead to life-threatening, intractable right ventricular heart failure (HF). In particular, children with hypoplastic left heart syndrome have a 10 year transplant-free survival rate of 50-75% despite palliative surgical repair. Currently, no effective stem-cell based treatments are available for pediatric HF. Recent stem-cell based clinical trials have been limited by poor differentiation rates and low cell retention. Additionally, we have shown that human cardiac progenitor cells (hCPCs) have reduced regenerative potential as they age, starting as early as 1 year old. We propose the aggregation of CPCs into scaffold-free spheres to improve the differentiation of child CPCs into mature cardiac phenotypes by enhancing intercellular Notch signaling. Notch signaling activity has been implicated in the regulation of CPC fate decisions and prior research in our lab has shown that intramyocardial delivery of Notch-ligand containing hydrogels improves cardiac function. Child CPC spheres were produced at a size of 1500 cells per sphere using a microwell array and cultured in suspension. Using immunohistochemistry, we showed that aggregation of CPCs increased Notch1 expression compared to parallel monolayer cultures. This effect is not limited to CPCs and was recapitulated in spheres of Chinese hamster ovarian cells transfected with Notch1-YFP. Additionally, Notch signaling pathway gene array data showed increased expression of the Notch-cleaving metalloprotease ADAM10 (3.6-fold) and Notch ligand DLL1 (25.0-fold) in CPC spheres by 3 days in culture compared to monolayer cultures. By 14 days in culture, we showed that aggregation of CPCs robustly increases the expression of the GATA4, a cardiac transcription factor associated with angiogenesis, and VEGFR1, an early marker of endothelial lineage commitment. Based on our results, we hypothesize that aggregation of CPCs into spheroids increases endothelial differentiation via a Notch-dependent mechanism. Transplantation of CPC spheres may improve cardiac function in vivo compared to transplantation of single CPCs. The results from our project will facilitate the development of autologous stem-cell based therapies for pediatric HF.


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