{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T04:09:17Z","timestamp":1773288557220,"version":"3.50.1"},"reference-count":27,"publisher":"Proceedings of the National Academy of Sciences","issue":"19","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2006,5,9]]},"abstract":"<jats:p>\n                    Type IV collagen is a predominant component of basement membranes, and glomeruli of a kidney filter \u224870\u201390 liters of plasma every day through a specialized glomerular basement membrane (GBM). In Alport syndrome, a progressive disease primarily affecting kidneys, mutations in GBM-associated type IV collagen genes (COL4A3, COL4A4, or COL4A5) lead to basement membrane structural defects, proteinuria, renal failure, and an absence of all three GBM collagen triple helical chains because of obligatory posttranslational assembly requirements. Here, we demonstrate that transplantation of wild-type bone marrow (BM) into irradiated COL4A3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice results in a possible recruitment of BM-derived progenitor cells as epithelial cells (podocytes) and mesangial cells within the damaged glomerulus, leading to a partial restoration of expression of the type IV collagen \u03b13 chain with concomitant emergence of \u03b14 and \u03b15 chain expression, improved glomerular architecture associated with a significant reduction in proteinuria, and improvement in overall kidney histology compared with untreated COL4A3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice or irradiated COL4A3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice with BM from adult COL4A3\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. The \u03b13(IV) collagen produced by BM-derived podocytes integrates into the GBM and associates with other \u03b1-chains to form type IV collagen triple helical networks. This study demonstrates that BM-derived stem cells can offer a viable strategy for repairing basement membrane defects and conferring therapeutic benefit for patients with Alport syndrome.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0601436103","type":"journal-article","created":{"date-parts":[[2006,4,28]],"date-time":"2006-04-28T20:39:51Z","timestamp":1146256791000},"page":"7321-7326","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":186,"title":["Bone-marrow-derived stem cells repair basement membrane collagen defects and reverse genetic kidney disease"],"prefix":"10.1073","volume":"103","author":[{"given":"Hikaru","family":"Sugimoto","sequence":"first","affiliation":[{"name":"*Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}]},{"given":"Thomas M.","family":"Mundel","sequence":"additional","affiliation":[{"name":"*Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}]},{"given":"Malin","family":"Sund","sequence":"additional","affiliation":[{"name":"*Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}]},{"given":"Liang","family":"Xie","sequence":"additional","affiliation":[{"name":"*Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"}]},{"given":"Dominic","family":"Cosgrove","sequence":"additional","affiliation":[{"name":"Boys Town National Research Hospital, Omaha, NE 68131;"}]},{"given":"Raghu","family":"Kalluri","sequence":"additional","affiliation":[{"name":"*Division of Matrix Biology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215;"},{"name":"Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215;"},{"name":"Harvard\u2013Massachusetts Institute of Technology Division of Health Sciences and Technology, Boston, MA 02215;"},{"name":"Division of Nephrology, Children's Hospital Boston, Boston, MA 02215; and"},{"name":"**Harvard Stem Cell Institute, Cambridge, MA 02138"}]}],"member":"341","published-online":{"date-parts":[[2006,5,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119431"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra022296"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.10.23.2981"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.2349482"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1981.tb05690.x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1094"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.135.5.1403"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.17.12719"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/00005792-199909000-00005"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65063-8"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204806200"},{"key":"e_1_3_3_12_2","first-page":"1065","volume":"437","year":"2005","unstructured":"Nature 437, 1065 (2005).","journal-title":"Nature"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-05-1684"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00328-2"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/35070587"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/81326"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/43919"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2942005pe37"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2701"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.2001.0285"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1634\/stemcells.22-1-86"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C300012200"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V103435"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s001250051088"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64802-X"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.1999.00744.x"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98618-7"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0601436103","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T15:16:01Z","timestamp":1649776561000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0601436103"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,9]]},"references-count":27,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2006,5,9]]}},"alternative-id":["10.1073\/pnas.0601436103"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0601436103","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.14697.472214","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5,9]]},"assertion":[{"value":"2006-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2006-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}