RRC ID 63049
著者 Fujimoto T, Yamanaka S, Tajiri S, Takamura T, Saito Y, Matsumoto N, Matsumoto K, Tachibana T, Okano HJ, Yokoo T.
タイトル Generation of Human Renal Vesicles in Mouse Organ Niche Using Nephron Progenitor Cell Replacement System.
ジャーナル Cell Rep
Abstract Animal fetuses may be used for the regeneration of human organs. We have previously generated a transgenic mouse model that allows diphtheria toxin (DT)-induced ablation of Six2-positive nephron progenitor cells (NPCs). Elimination of existing native host NPCs enables their replacement with donor NPCs, which can generate neo-nephrons. However, this system cannot be applied to human NPCs, because DT induces apoptosis in human cells. Therefore, the present study presents a transgenic mouse model for the ablation of NPCs using tamoxifen, which does not affect human cells. Using this system, we successfully regenerate interspecies neo-nephrons, which exhibit urine-producing abilities, from transplanted rat NPCs in a mouse host. Transplantation of human induced pluripotent stem cell (iPSC)-derived NPCs results in differentiation into renal vesicles, which connect to the ureteric bud of the host. Thus, we demonstrate the possibility of the regeneration of human kidneys derived from human iPSC-derived NPCs via NPC replacement.
巻・号 32(11)
ページ 108130
公開日 2020-9-15
DOI 10.1016/j.celrep.2020.108130
PII S2211-1247(20)31119-0
PMID 32937125
MeSH Animals Homeodomain Proteins / metabolism Humans Induced Pluripotent Stem Cells / cytology Induced Pluripotent Stem Cells / drug effects Mice, Inbred C57BL Nephrons / cytology* Nephrons / drug effects Nephrons / ultrastructure Organ Specificity Rats, Sprague-Dawley Regeneration* / drug effects Species Specificity Stem Cells / cytology* Stem Cells / drug effects Stem Cells / metabolism Tamoxifen / pharmacology Transcription Factors / metabolism Urinary Bladder / embryology Urination / drug effects
IF 8.109
リソース情報
ヒト・動物細胞 201B7(HPS0063)