オカノ テルオ   Okano Teruo
  岡野 光夫
   所属   医学研究科 医学研究科 (医学部医学科をご参照ください)
   職種   評議員
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 Clinically relevant mesenchymal stem/stromal cell sheet transplantation method for kidney disease.
掲載誌名 正式名:Tissue engineering. Part C, Methods
略  称:Tissue Eng Part C Methods
ISSNコード:19373392/19373384
掲載区分国外
巻・号・頁 29(2),pp.54-62
著者・共著者 OKA Masatoshi†, KAMEISHI Sumako*, Cho Yun-Kyoung, Song Sun U, Grainger David W, OKANO Teruo*
担当区分 最終著者,責任著者
発行年月 2023/01
概要 Chronic Kidney Disease (CKD) is the irreversible loss of nephron function, leading to a build-up of toxins, prolonged inflammation, and ultimately fibrosis. Currently, no effective therapies exist to treat CKD due to its complex pathophysiology. Mesenchymal stem/stromal cell (MSC) transplantation is a promising strategy to treat kidney diseases, and multiple clinical trials are currently ongoing. We previously demonstrated that rat bone marrow-derived MSC (BMSC) sheets transplanted onto surgically de-capsulated kidney exert therapeutic effects that suppressed renal fibrosis progression based on enhanced vascularization. However, there are clinical concerns about kidney decapsulation such as impaired glomerular filtration rate and Na+ ion and H2O excretion, leading to kidney dysfunction. Therefore, for transitioning from basic research to translational research using cell sheet therapy for kidney disease, it is essential to develop a new cell sheet transplantation strategy without kidney decapsulation. Significantly, we employed cell sheets engineered from clinical-grade human clonal BMSC (cBMSC) and transplanted these onto intact renal capsule to evaluate their therapeutic ability in the rat ischemia reperfusion injury (IRI) model. Histological analysis 1-day post-surgery showed that cBMSC sheets engrafted well onto intact renal capsule. Interestingly, some grafted cBMSCs migrated into the renal parenchyma. At 1- to 3-days post-surgery (acute stage), grafted cBMSC sheets prevented tubular epithelial cell injury. At 28-days post-surgery (chronic phase), we observed that grafted cBMSC sheets suppressed renal fibrosis in the rat IRI model. Taken together, engineered cBMSC sheet transplantation onto intact renal capsule suppresses tubular epithelial cell injury and renal fibrosis, supporting further development as a possible clinically relevant strategy.
DOI 10.1089/ten.TEC.2022.0200
PMID 36719774