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 decapsulated 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 postsurgery showed that cBMSC sheets engrafted well onto intact renal
capsule. Interestingly, some grafted cBMSCs migrated into the renal parenchyma. At 1-3 days postsurgery (acute stage), grafted cBMSC sheets prevented tubular epithelial cell injury. At 28 days postsurgery (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. Impact statement
Chronic kidney disease (CKD) produces irreversible loss of nephron function, leading to
toxemia, prolonged
inflammation, and ultimately kidney
fibrosis. Currently, no
therapies exist to effectively treat CKD due to its complex pathophysiology. Mesenchymal stem/stromal cells (MSCs) are widely known to secret therapeutic paracrine factors, which is expected to provide a new effective
therapy for unmet medical needs. However, unsatisfied MSC quality and administration methods to patients limit their
therapeutic effects. In this study, we engineered clonal bone marrow-derived MSC sheets and established clinically relevant cell sheet
transplantation strategy to treat renal
fibrosis, which would improve MSC treatment for
kidney disease.