Extracellular vesicles from human urine-derived stem cells prevent osteoporosis by transferring CTHRC1 and OPG

Abstract

Osteoporosis is a debilitating bone disease affecting millions of people. Here, we used human urine-derived stem cells (USCs), which were noninvasively harvested from unlimited and easily available urine, as a “factory” to obtain extracellular vesicles (USC-EVs) and demonstrated that the systemic injection of USC-EVs effectively alleviates bone loss and maintains bone strength in osteoporotic mice by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. More importantly, the anti-osteoporotic properties of USC-EVs are not notably disrupted by the age, gender, or health condition (with or without osteoporosis) of the USC donor. Mechanistic studies determined that collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) proteins are enriched in USC-EVs and required for USC-EV-induced pro-osteogenic and anti-osteoclastic effects. Our results suggest that autologous USC-EVs represent a promising novel therapeutic agent for osteoporosis by promoting osteogenesis and inhibiting osteoclastogenesis by transferring CTHRC1 and OPG.

Urine-Derived Stem Cells: Applications in Regenerative and Predictive Medicine

“…Chen et al demonstrated that systemic injection of extracellular vesicles from human-harvested UDSC prevented osteoporosis in ovariectomized mice by transferring collagen triple-helix repeat containing 1 (CTHRC1) and osteoprotegerin (OPG) [71]. The same strategy was done to improve erectile dysfunction in a diabetic rat model-this time, by means of transferring pro-angiogenic miRNA [72]-and to decrease kidney injury in a diabetic rat model by transferring pro-vascular regeneration and cell protection factors, including growth factor, transforming growth factor-β1, angiogenin and bone morphogenetic protein-7 [73]. In the same disease context, Jin et al demonstrated that exosomes from UDSC attenuated podocyte apoptosis in a mouse model of diabetes, besides decreasing apoptosis and increasing autophagy fluxes when added to MPC5 cells exposed to hyperglycemia.…”

Urine-derived stem/progenitor cells: A focus on their characterization and potential

“…Regarding tissue repair, exosomes from USCs have been tested in different clinical contexts. For bone regeneration, Chen et al[ 92 ] showed that 100 μg of human USC-extracellular vesicles (EVs) (obtained from USC-conditioned medium) effectively alleviated bone loss and maintained bone strength in osteoporotic mice (ovariectomized mice) by enhancing osteoblastic bone formation and suppressing osteoclastic bone resorption. Interestingly, the authors demonstrated that the antiosteoporotic properties of USC-EVs were not noticeably disturbed by the age, gender or health condition (with or without osteoporosis) of the USC donor, as USC-EVs from a healthy boy, healthy adult man and woman and postmenopausal osteoporotic woman could induce notable antiosteoporotic effects.…”

Pharmacotherapy to gene editing: potential therapeutic approaches for Hutchinson–Gilford progeria syndrome

“…There are several reports on the treatment of agingrelated bone and cardiovascular disorders with EVs in in vitro and in vivo conditions (Alibhai et al 2018;Chen et al 2019;Yuan et al 2018). EVs derived from a variety of stem cell and even nonstem cell sources have shown potential for preventing post-myocardial infarction (MI) remodeling in animal models.…”

“…In a recent study, stem cells obtained from human urine (USCs) were used for the production of EVs (USC-EVs) that could prevent bone loss and promote osteogenesis in a mouse model of osteoporosis (Chen et al 2019). USC-EVs have also demonstrated woundhealing ability in diabetic mice (Chen et al 2018).…”