{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T14:02:13Z","timestamp":1775656933372,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100006034","name":"University of Southern California","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006034","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biomedical Materials Res"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Autosomal recessive polycystic kidney disease (ARPKD) is a severe inherited disorder caused primarily by mutations in\n                    <jats:italic>PKHD1<\/jats:italic>\n                    and in a minority of cases,\n                    <jats:italic>CYS1<\/jats:italic>\n                    . These genes encode fibrocystin and cystin, respectively. ARPKD typically manifests in infancy with enlarged kidneys, progressive cyst formation, and an estimated peri\u2010natal high mortality rate of 20%. Given the lack of efficient therapies and the genetic complexity of many rare diseases such as ARPKD, strategies that restore functional proteins defective in the disease may offer a disease\u2010modifying approach. Urinary extracellular vesicles (uEVs) are naturally secreted by renal and urinary tract cells and contain functional kidney proteins, including fibrocystin and cystin. As such, uEVs may be capable of supplementing these missing proteins and delivering them directly to diseased cells in ARPKD. To investigate the therapeutic potential of uEVs for ARPKD, we first isolated and characterized uEVs from healthy mouse urine by nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting for EV markers. PCR confirmed the presence of\n                    <jats:italic>Cys1<\/jats:italic>\n                    and\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    mRNAs in uEVs, while cellular uptake was verified by fluorescence microscopy and flow cytometry in collecting duct epithelial cells (mpkCCDc14). In\u00a0vitro, uEV treatment enhanced\n                    <jats:italic>Cys1<\/jats:italic>\n                    and\n                    <jats:italic>Pkhd1<\/jats:italic>\n                    levels in healthy cells, and rescued\n                    <jats:italic>Cys1<\/jats:italic>\n                    levels in\n                    <jats:italic>Cys1<\/jats:italic>\n                    \u2010deficient cells, derived from\n                    <jats:italic>Cys1<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>cpk\/cpk<\/jats:italic>\n                    <\/jats:sup>\n                    (\n                    <jats:italic>cpk<\/jats:italic>\n                    ) mice. Upon administration in the\n                    <jats:italic>cpk<\/jats:italic>\n                    mouse model of ARPKD, uEV improved the survival rate in\n                    <jats:italic>cpk<\/jats:italic>\n                    mice. Furthermore, in utero administration of uEVs demonstrated accumulation in the fetal kidney and enhanced\n                    <jats:italic>Cys1<\/jats:italic>\n                    level following intra\u2010amniotic (IA) administration, highlighting the feasibility of prenatal therapy for the most severe cases of ARPKD that are lethal in utero or within the first 24\u201348\u2009h after birth. Taken together, our findings reveal that uEVs represent a promising therapeutic modality for ARPKD, capable of restoring deficient CYS1 protein levels\u00a0and mitigating disease progression.\n                  <\/jats:p>","DOI":"10.1002\/jbma.70047","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T04:57:28Z","timestamp":1770613048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation of Urinary Extracellular Vesicles as Novel and Safe Therapeutics for Autosomal Recessive Polycystic Kidney Disease (\n                    <scp>ARPKD<\/scp>\n                    )"],"prefix":"10.1002","volume":"114","author":[{"given":"Yi","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huihua","family":"Xing","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ali","family":"Osouli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Guay\u2010Woodford","sequence":"additional","affiliation":[{"name":"Divisions of Nephrology and Genetics Research Institute and Department of Pediatrics, Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7726-5555","authenticated-orcid":false,"given":"Eun Ji","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of Southern California  Los Angeles California USA"},{"name":"Department of Medicine, Division of Nephrology and Hypertension Keck School of Medicine, University of Southern California  Los Angeles California USA"},{"name":"Department of Chemical Engineering and Materials Science University of Southern California  Los Angeles California USA"},{"name":"Department of Surgery, Division of Vascular Surgery and Endovascular Therapy Keck School of Medicine, University of Southern California  Los Angeles California USA"},{"name":"Department of Stem Cell Biology and Regenerative Medicine University of Southern California  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,2,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2017.00080"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2706-2"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/tri.12098"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2023.1270980"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-013-2634-1"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.md.0000200165.90373.9a"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.2147\/PHMT.S271209"},{"issue":"6","key":"e_1_2_11_9_1","first-page":"e4842","article-title":"Tolvaptan\u2010Induced Liver Injury: Who Is at Risk? 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