Cargando…

Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model

AIMS/INTRODUCTION: Adipose‐derived mesenchymal stem cell (ASC) transplantation is a promising therapy for diabetic nephropathy (DN). However, intravascular administration of ASCs is associated with low engraftment in target organs. Therefore, we considered applying the cell sheet technology to ASCs....

Descripción completa

Detalles Bibliográficos
Autores principales: Takemura, Shunsuke, Shimizu, Tatsuya, Oka, Masatoshi, Sekiya, Sachiko, Babazono, Tetsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232293/
https://www.ncbi.nlm.nih.gov/pubmed/31622047
http://dx.doi.org/10.1111/jdi.13164
_version_ 1783535354399162368
author Takemura, Shunsuke
Shimizu, Tatsuya
Oka, Masatoshi
Sekiya, Sachiko
Babazono, Tetsuya
author_facet Takemura, Shunsuke
Shimizu, Tatsuya
Oka, Masatoshi
Sekiya, Sachiko
Babazono, Tetsuya
author_sort Takemura, Shunsuke
collection PubMed
description AIMS/INTRODUCTION: Adipose‐derived mesenchymal stem cell (ASC) transplantation is a promising therapy for diabetic nephropathy (DN). However, intravascular administration of ASCs is associated with low engraftment in target organs. Therefore, we considered applying the cell sheet technology to ASCs. In this study, ASC sheets were directly transplanted into the kidneys of a DN rat model, and therapeutic consequences were analyzed. MATERIALS AND METHODS: Adipose‐derived mesenchymal stem cells were isolated from adipose tissues of 7‐week‐old enhanced green fluorescent protein rats, and ASC sheets were prepared using a temperature‐responsive culture dish. A DN rat model was established from 5‐week‐old Spontaneously Diabetic Torii fatty rats. Seven‐week‐old DN rats (n = 21) were assigned to one of the following groups: sham‐operated (n = 6); ASC suspension (6.0 × 10(6) cells/mL) administered intravenously (n = 7); six ASC sheets transplanted directly into the kidney (n = 8). The therapeutic effect of the cell sheets was determined based on urinary biomarker expression and histological analyses. RESULTS: The ASC sheets survived under the kidney capsule of the DN rat model for 14 days after transplantation. Furthermore, albuminuria and urinary tumor necrosis factor‐α levels were significantly lower in the ASC sheets transplanted directly into the kidney group than in the sham‐operated and ASC suspension administered intravenously groups (P < 0.05). Histologically, the ASC sheets transplanted directly into the kidney group presented mild atrophy of the proximal tubule and maintained the renal tubular structure. CONCLUSIONS: Transplantation of ASC sheets directly into the kidney improved transplantation efficiency and suppressed renal injury progression. Therefore, the ASC sheet technology might be a promising novel treatment for DN.
format Online
Article
Text
id pubmed-7232293
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-72322932020-05-19 Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model Takemura, Shunsuke Shimizu, Tatsuya Oka, Masatoshi Sekiya, Sachiko Babazono, Tetsuya J Diabetes Investig Articles AIMS/INTRODUCTION: Adipose‐derived mesenchymal stem cell (ASC) transplantation is a promising therapy for diabetic nephropathy (DN). However, intravascular administration of ASCs is associated with low engraftment in target organs. Therefore, we considered applying the cell sheet technology to ASCs. In this study, ASC sheets were directly transplanted into the kidneys of a DN rat model, and therapeutic consequences were analyzed. MATERIALS AND METHODS: Adipose‐derived mesenchymal stem cells were isolated from adipose tissues of 7‐week‐old enhanced green fluorescent protein rats, and ASC sheets were prepared using a temperature‐responsive culture dish. A DN rat model was established from 5‐week‐old Spontaneously Diabetic Torii fatty rats. Seven‐week‐old DN rats (n = 21) were assigned to one of the following groups: sham‐operated (n = 6); ASC suspension (6.0 × 10(6) cells/mL) administered intravenously (n = 7); six ASC sheets transplanted directly into the kidney (n = 8). The therapeutic effect of the cell sheets was determined based on urinary biomarker expression and histological analyses. RESULTS: The ASC sheets survived under the kidney capsule of the DN rat model for 14 days after transplantation. Furthermore, albuminuria and urinary tumor necrosis factor‐α levels were significantly lower in the ASC sheets transplanted directly into the kidney group than in the sham‐operated and ASC suspension administered intravenously groups (P < 0.05). Histologically, the ASC sheets transplanted directly into the kidney group presented mild atrophy of the proximal tubule and maintained the renal tubular structure. CONCLUSIONS: Transplantation of ASC sheets directly into the kidney improved transplantation efficiency and suppressed renal injury progression. Therefore, the ASC sheet technology might be a promising novel treatment for DN. John Wiley and Sons Inc. 2019-11-06 2020-05 /pmc/articles/PMC7232293/ /pubmed/31622047 http://dx.doi.org/10.1111/jdi.13164 Text en © 2019 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Articles
Takemura, Shunsuke
Shimizu, Tatsuya
Oka, Masatoshi
Sekiya, Sachiko
Babazono, Tetsuya
Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
title Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
title_full Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
title_fullStr Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
title_full_unstemmed Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
title_short Transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
title_sort transplantation of adipose‐derived mesenchymal stem cell sheets directly into the kidney suppresses the progression of renal injury in a diabetic nephropathy rat model
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7232293/
https://www.ncbi.nlm.nih.gov/pubmed/31622047
http://dx.doi.org/10.1111/jdi.13164
work_keys_str_mv AT takemurashunsuke transplantationofadiposederivedmesenchymalstemcellsheetsdirectlyintothekidneysuppressestheprogressionofrenalinjuryinadiabeticnephropathyratmodel
AT shimizutatsuya transplantationofadiposederivedmesenchymalstemcellsheetsdirectlyintothekidneysuppressestheprogressionofrenalinjuryinadiabeticnephropathyratmodel
AT okamasatoshi transplantationofadiposederivedmesenchymalstemcellsheetsdirectlyintothekidneysuppressestheprogressionofrenalinjuryinadiabeticnephropathyratmodel
AT sekiyasachiko transplantationofadiposederivedmesenchymalstemcellsheetsdirectlyintothekidneysuppressestheprogressionofrenalinjuryinadiabeticnephropathyratmodel
AT babazonotetsuya transplantationofadiposederivedmesenchymalstemcellsheetsdirectlyintothekidneysuppressestheprogressionofrenalinjuryinadiabeticnephropathyratmodel