Urine-derived Stem Cells: An Exciting New Source of Autologous Endothelial Cells?

Review of “Human Urine-Derived Stem Cell Differentiation to Endothelial Cells with Barrier Function and Nitric Oxide Production” from STEM CELLS Translational Medicine by Stuart P. Atkinson

The application of tissue-engineered vascular grafts constructed with autologous ECs in combination with suitable scaffolds may avoid many of the problems associated with revascularization approaches employing autologous vessels or allogenic/synthetic vascular grafts. As a means to generate sufficient autologous ECs, researchers from the laboratory of Yuanyuan Zhang (Wake Forest School of Medicine, Winston-Salem, NC, USA) recently assessed the possible differentiation of ECs from urine-derived stem cells (USCs), cells originating from the parietal cells in kidney glomeruli that possess robust proliferative abilities, multipotent differentiation capacity, and robust paracrine-acting effects [1-4].

Reporting in STEM CELLS Translational Medicine, Liu et al. now reveal that differentiation of USCs generates ECs with robust endothelial function in vitro and endothelial potential in vivo, thereby suggesting this approach as a non-invasive, simple, and low-cost method [5] to produce sufficient autologous ECs for applications in tissue-engineered vascular regeneration or the repair of endothelial dysfunction [6].

Differentiation of USCs in endothelial medium generated EC-like cells by day 14 that displayed endothelial characteristics at the morphological, ultrastructural (tight junction formation), and functional marker expression levels (e.g., CD31, vWF, and eNOS). In vitro, USC-ECs displayed many endothelial cell-capabilities, including the creation of intricate tubular networks in MatrigelTM, the uptake of acetylated-low-density lipoprotein, the ability to migrate and invade, the induction of permeability barrier function (related to tight junction formation), and the production of nitric oxide (NO). Importantly, USCs subcutaneously injected into nude mice expressed high levels of EC markers when induced to undergo endothelial differentiation by co-grafted VEGF alginate microbeads (See Figure), suggesting a robust in vivo endothelial potential.

Overall, the authors provide substantial evidence that non-invasively collected USCs represent an exciting new source of autologous ECs for applications in tissue-engineered vascular regeneration or repair of endothelial dysfunction.

For more on the massive potential of urine-derived stem cells and their regenerative applications, stay tuned to the Stem Cells Portal!

Discussion Points

• How can we further improve EC differentiation efficiency?
• Can USCs be efficiently differentiated into other therapeutically relevant cell types?
• What barriers exist to the clinical application of USC-derived cells?

References

1. Bharadwaj S, Liu G, Shi Y, et al., Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology. Stem Cells 2013;31:1840-56.
2. Zhang D, Wei G, Li P, et al., Urine-derived stem cells: A novel and versatile progenitor source for cell-based therapy and regenerative medicine. Genes Dis 2014;1:8-17.
3. Qin D, Long T, Deng J, et al., Urine-derived stem cells for potential use in bladder repair. Stem Cell Res Ther 2014;5:69.
4. Liu G, Pareta RA, Wu R, et al., Skeletal myogenic differentiation of urine-derived stem cells and angiogenesis using microbeads loaded with growth factors. Biomaterials 2013;34:1311-26.
5. Zhang Y, McNeill E, Tian H, et al., Urine derived cells are a potential source for urological tissue reconstruction. J Urol 2008;180:2226-33.
6. Liu G, Wu R, Yang B, et al., Human Urine-Derived Stem Cell Differentiation to Endothelial Cells with Barrier Function and Nitric Oxide Production. STEM CELLS Translational Medicine 2018;7:686-698.