title: Kidney regeneration by non-platelet RNA-containing particle-derived cells.
abstract: We found a group of non-platelet RNA-containing particles (NPRCPs) in human umbilical cord blood. These particles can aggregate, fuse and become non-nucleated cells when cocultured with nucleated cells in vitro. The non-nucleated cells further differentiate into nucleated cells expressing octamer binding transcription factor 4 (OCT4). The NPRCPs are approximately 1-5 μm in diameter, have a thin bilayer membrane, contain short RNAs and microRNAs and express OCT4, sex-determining region Y 2 (SOX2) and DEAD box polypeptide 4 (DDX4). To confirm the function of NPRCPs in vivo, we examined the effects of tail vein-injected green fluorescent protein (GFP)-labelled NPRCPs on mouse kidneys damaged by prior ischaemia and reperfusion from Day 1 to Week 6. Within 1 day of injection of NPRCPs, immunofluorescence and immunohistochemistry revealed a large number of extravasated NPRCPs in the renal calyces, damaged glomeruli and duct tubules. During the course of regeneration, NPRCPs fused into large, non-nucleated cellular structures that further became large nucleated cells to regenerate multicellular kidney tubules. In addition, many NPRCPs became tiny nucleated cellular structures that further differentiated into interstitial cells in connective tissue. The extravasated NPRCPs also arranged themselves into non-cell glomerular structures before further regenerating into nucleated cells of the glomerulus. In conclusion, the results demonstrate that, via different patterns of differentiation, NPRCP-derived cells can regenerate mouse kidney tissue damaged by ischaemia.
authors.affiliation: Beijing Khasar Medical Technology, Beijing, China.
authors.forename: Wuyi
authors.initials: W
authors.lastname: Kong
authors.forename: Mu
authors.initials: M
authors.lastname: Nuo
authors.forename: Xiao Ping
authors.initials: XP
authors.lastname: Zhu
authors.forename: Xiu Juan
authors.initials: XJ
authors.lastname: Han
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
mesh_terms: D053687:Adult Stem Cells / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D000818:Animals; D002454:Cell Differentiation; D054338:Cell Transdifferentiation; D055252:Cell-Derived Microparticles / Q000378:metabolism / Q000637:transplantation* / Q000648:ultrastructure; D002478:Cells, Cultured; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000503:physiopathology; D007668:Kidney / Q000473:pathology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D012313:RNA / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012038:Regeneration; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D055748:SOXB1 Transcription Factors / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011994:Recombinant Proteins; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D049452:Green Fluorescent Proteins; D012313:RNA; C498288:DDX4 protein, human; D053487:DEAD-box RNA Helicases
keywords: DEAD box polypeptide 4; acute ischaemia; glomerulus; kidney tubules; non-platelet RNA-containing particles; octamer binding transcription factor 4; sex-determining region Y 2; stem cells