Open AccessHuman Urine‐Derived Stem Cell Differentiation to Endothelial Cells with Barrier Function and Nitric Oxide Production
Author(s) -
Liu Guihua,
Wu Rongpei,
Yang Bin,
Deng Chunhua,
Lu Xiongbing,
Walker Stephen J.,
Ma Peter X.,
Mou Steve,
Atala Anthony,
Zhang Yuanyuan
Publication year - 2018
Publication title -
stem cells translational medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.781
H-Index - 71
eISSN - 2157-6580
pISSN - 2157-6564
DOI - 10.1002/sctm.18-0040
Subject(s) - stem cell , microbiology and biotechnology , endothelial stem cell , cellular differentiation , induced pluripotent stem cell , embryonic stem cell , biology , adult stem cell , tissue engineering , bone marrow , immunology , in vitro , biochemistry , genetics , gene
Endothelial cells (ECs) play a key role in revascularization within regenerating tissue. Stem cells are often used as an alternative cell source when ECs are not available. Several cell types have been used to give rise to ECs, such as umbilical cord vessels, or differentiated from somatic stem cells, embryonic, or induced pluripotent stem cells. However, the latter carry the potential risk of chronic immune rejection and oncogenesis. Autologous endothelial precursors are an ideal resource, but currently require an invasive procedure to obtain them from the patient's own blood vessels or bone marrow. Thus, the goal of this study was to determine whether urine‐derived stem cells (USCs) could differentiate into functional ECs in vitro. Urine‐derived cells were then differentiated into cells of the endothelial lineage using endothelial differentiation medium for 14 days. Changes in morphology and ultrastructure, and functional endothelial marker expression were assessed in the induced USCs in vitro. Grafts of the differentiated USCs were then subcutaneously injected into nude mice. Induced USCs expressed significantly higher levels of specific markers of ECs (CD31, vWF, eNOS) in vitro and in vivo, compared to nondifferentiated USCs. In addition, the differentiated USC formed intricate tubular networks and presented similar tight junctions, and migration and invasion ability, as well as ability to produce nitric oxide (NO) compared to controls. Using USCs as autologous EC sources for vessel, tissue engineering strategies can yield a sufficient number of cells via a noninvasive, simple, and low‐cost method suitable for rapid clinical translation. Stem Cells Translational Medicine 2018 S tem C ells T ranslational M edicine 2018;7:686–698