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OKANO Teruo
Department Research Institutes and Facilities, Research Institutes and Facilities Position |
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| Article types | Original article |
| Language | English |
| Peer review | Peer reviewed |
| Title | Clinically relevant mesenchymal stem/stromal cell sheet transplantation method for kidney disease. |
| Journal | Formal name：Tissue engineering. Part C, Methods Abbreviation：Tissue Eng Part C Methods ISSN code：19373392/19373384 |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 29(2),pp.54-62 |
| Author and coauthor | OKA Masatoshi†, KAMEISHI Sumako*, Cho Yun-Kyoung, Song Sun U, Grainger David W, OKANO Teruo* |
| Authorship | Last author,Corresponding author |
| Publication date | 2023/01 |
| Summary | 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 |