scholarly journals Efficient Differentiation of Human Pluripotent Stem Cells to Endothelial Cells

2018 ◽  
Vol 98 (1) ◽  
pp. e64 ◽  
Author(s):  
Mingxia Gu
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Pluripotent Stem Cells ◽  
Human Pluripotent Stem Cells

scholarly journals Human pluripotent stem cell-derived brain pericyte-like cells induce blood-brain barrier properties

2018 ◽  
Author(s):  
Matthew J. Stebbins ◽  
Benjamin D. Gastfriend ◽  
Scott G. Canfield ◽  
Ming-Song Lee ◽  
Drew Richards ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Blood Brain Barrier ◽  
Pluripotent Stem Cells ◽  
Neurovascular Unit ◽  
Human Pluripotent Stem Cells ◽  
Brain Barrier ◽  
Blood Brain ◽  
Brain Pericytes ◽  
The Brain

ABSTRACTBrain pericytes play an important role in the formation and maintenance of the neurovascular unit (NVU), and their dysfunction has been implicated in central nervous system (CNS) disorders. While human pluripotent stem cells (hPSCs) have been used to model other components of the NVU including brain microvascular endothelial cells (BMECs), astrocytes, and neurons, cells having brain pericyte-like phenotypes have not been described. In this study, we generated neural crest stem cells (NCSCs), the embryonic precursor to forebrain pericytes, from human pluripotent stem cells (hPSCs) and subsequently differentiated NCSCs to brain pericyte-like cells. The brain pericyte-like cells expressed marker profiles that closely resembled primary human brain pericytes, and they self-assembled with endothelial cells to support vascular tube formation. Importantly, the brain pericyte-like cells induced blood-brain barrier (BBB) properties in BMECs, including barrier enhancement and reduction of transcytosis. Finally, brain pericyte-like cells were incorporated with iPSC-derived BMECs, astrocytes, and neurons to form an isogenic human NVU model that should prove useful for the study of the BBB in CNS health, disease, and therapy.

The Balance of Positive and Negative Effects of TGF-Beta Signaling Regulates the Hemangioblast Development in Human Pluripotent Stem Cells

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1220-1220
Author(s):  
Hao Bai ◽  
Yin-Liang Xie ◽  
Yong-Xing Gao ◽  
Tao Cheng ◽  
Zack Z Wang
Keyword(s):  
Stem Cells ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Pluripotent Stem Cells ◽  
Hematopoietic Cells ◽  
Human Pluripotent Stem Cells ◽  
Embryoid Bodies ◽  
Mesoderm Induction ◽  
Tgf Beta ◽  
Free System

Abstract Abstract 1220 Derived from mesoderm precursors, hemangioblasts are bipotential common progenitors of hematopoietic cells and endothelial cells. The regulatory events controlling human hemangioblast development are largely unknown. Our previous study demonstrated that CD34 progenitors from human embryonic stem cells (hESCs) contain a population of cells that give rise to hematopoietic cells and endothelial cells. In this study, we established a serum-free and feeder-free system to investigate the signals that direct differentiation of human pluripotent stem cells (hPSCs), including hESCs and induced-pluripotent stem cells (hiPSCs). The hemangioblast development in hPSCs was established in three major steps: i) the formation of uniformed embryoid bodies (EBs) in hanging-drops, ii) the development of multipotential mesoderm precursors in cultivation of EBs, and iii) the generation of CD34+CD31+VE-cadherin+ progenitors, which have hemangioblast potential to give rise to both hematopoietic and endothelial cells (via hemogenic endothelium). The hESC-derived hematopoietic cells expressed CD41, CD61, CD117, CD71, and CD235a. The endothelial cells were CD31+ and VE-cadherin+ cells. We found that inhibition of Rho-associated coiled-coil forming protein serine/threonine kinase (ROCK) by Y27632 was critical for hanging-drop EB formation. Transforming growth factor beta (TGF-beta) is a key regulator of hematopoiesis with potent inhibitory effects on progenitor and stem cell proliferation. The expression of TGF-beta was increased during hPSC differentiation. Inhibition of TGF-beta signaling by the TGF-beta inhibitor, SB431542, significantly decreased the efficiency of CD34+ progenitors, suggesting a crucial role of TGF-beta signaling in hPSC differentiation. To further investigate when TGF-beta signaling affects hPSC differentiation to CD34+ progenitors, we added TGF-beta inhibitor at different stages of hPSC differentiation. We found that TGF-beta signaling is required for the early mesoderm induction. Inhibition of TGFb signaling before hemangioblast commitment during PSC differentiation significantly decreases the frequency of hemangioblasts (CD34+/CD31+/VE-cadherin+ cells) and the expression of mesoderm markers, such as Brachyury, Tie1, EOMES, and MIXL1. On the other hand, inhibition of TGF-beta signaling after mesoderm induction increases the number of CD34+/CD31+/VE-cadherin+ cells. EdU cell proliferation assays indicated that the proliferation of CD34+ progenitors were not affected by SB431542, suggesting that TGF-beta signaling suppresses hemangioblast generation. Our study demonstrated that TGF-beta signaling has the double-edged effect on hPSC differentiation to hemangioblasts. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document