Bone marrow-derived mesenchymal stem cells transplantation ameliorates renal injury through anti-fibrotic and anti-inflammatory effects in chronic experimental renovascular disease
Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved..
BACKGROUND: Progressive renal fibrosis is an underlying pathological process of chronic kidney disease (CKD) evolution. This study aimed to evaluate the roles of bone-marrow-derived mesenchymal stem cells (MSC) in the remodeling of fibrotic kidney parenchyma in the two kidneys-one clip (2K1C) CKD animal model.
METHODS: Wistar rats were allocated into three groups: Sham, 2K1C, and 2K1C þ MSC. MSCs (106) were transplanted into the renal subcapsular region two weeks after clipping the left renal artery. Six weeks after clipping, left kidney samples were analyzed using histological and western blotting techniques. ANOVA tests were performed and differences between groups were considered statistically significant if p < 0.05.
RESULTS: Clipped kidneys of 2K1C rats displayed renal fibrosis, with excessive collagen deposition, glomerulosclerosis and renal basement membrane disruption. Clipped kidneys of 2K1C þ MSC rats showed preserved Bowman's capsule and tubular basement membranes, medullary tubules morphological reconstitution and reduced collagen deposits. Expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were elevated, whereas tissue inhibitor of MMPs (TIMP)-1 and TIMP-2 levels were decreased in clipped kidneys of 2K1C rats. MSCs transplantation restored these expression levels. Moreover, MSCs suppressed macrophages and myofibroblasts accumulation, as well as TNF-a expression in clipped kidneys of 2K1C animals. MSCs transplantation significantly increased IL-10 expression.
CONCLUSIONS: Transplanted MSCs orchestrate anti-fibrotic and anti-inflammatory events, which reverse renal fibrosis and promote renal morphological restoration. This study supports the notion that only one MSCs delivery into the renal subcapsular region represents a possible therapeutic strategy against renal fibrosis for CKD treatment.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:45 |
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| Enthalten in: |
Biomedical journal - 45(2022), 4 vom: 15. Aug., Seite 629-641 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Almeida, Aline [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 20.09.2022 Date Revised 07.10.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bj.2021.07.009 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM32877684X |
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| 100 | 1 | |a Almeida, Aline |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Bone marrow-derived mesenchymal stem cells transplantation ameliorates renal injury through anti-fibrotic and anti-inflammatory effects in chronic experimental renovascular disease |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a Copyright © 2021 Chang Gung University. Published by Elsevier B.V. All rights reserved. | ||
| 520 | |a BACKGROUND: Progressive renal fibrosis is an underlying pathological process of chronic kidney disease (CKD) evolution. This study aimed to evaluate the roles of bone-marrow-derived mesenchymal stem cells (MSC) in the remodeling of fibrotic kidney parenchyma in the two kidneys-one clip (2K1C) CKD animal model | ||
| 520 | |a METHODS: Wistar rats were allocated into three groups: Sham, 2K1C, and 2K1C þ MSC. MSCs (106) were transplanted into the renal subcapsular region two weeks after clipping the left renal artery. Six weeks after clipping, left kidney samples were analyzed using histological and western blotting techniques. ANOVA tests were performed and differences between groups were considered statistically significant if p < 0.05 | ||
| 520 | |a RESULTS: Clipped kidneys of 2K1C rats displayed renal fibrosis, with excessive collagen deposition, glomerulosclerosis and renal basement membrane disruption. Clipped kidneys of 2K1C þ MSC rats showed preserved Bowman's capsule and tubular basement membranes, medullary tubules morphological reconstitution and reduced collagen deposits. Expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 were elevated, whereas tissue inhibitor of MMPs (TIMP)-1 and TIMP-2 levels were decreased in clipped kidneys of 2K1C rats. MSCs transplantation restored these expression levels. Moreover, MSCs suppressed macrophages and myofibroblasts accumulation, as well as TNF-a expression in clipped kidneys of 2K1C animals. MSCs transplantation significantly increased IL-10 expression | ||
| 520 | |a CONCLUSIONS: Transplanted MSCs orchestrate anti-fibrotic and anti-inflammatory events, which reverse renal fibrosis and promote renal morphological restoration. This study supports the notion that only one MSCs delivery into the renal subcapsular region represents a possible therapeutic strategy against renal fibrosis for CKD treatment | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Chronic kidney disease | |
| 650 | 4 | |a Matrix metalloproteinase | |
| 650 | 4 | |a Mesenchymal stem cells | |
| 650 | 4 | |a Renal fibrosis | |
| 650 | 4 | |a Renovascular hypertension | |
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| 700 | 1 | |a Lira, Rafaelle |e verfasserin |4 aut | |
| 700 | 1 | |a Oliveira, Mariana |e verfasserin |4 aut | |
| 700 | 1 | |a Martins, Marcela |e verfasserin |4 aut | |
| 700 | 1 | |a Azevedo, Yanca |e verfasserin |4 aut | |
| 700 | 1 | |a Silva, Karina R |e verfasserin |4 aut | |
| 700 | 1 | |a Carvalho, Simone |e verfasserin |4 aut | |
| 700 | 1 | |a Cortez, Erika |e verfasserin |4 aut | |
| 700 | 1 | |a Stumbo, Ana Carolina |e verfasserin |4 aut | |
| 700 | 1 | |a Carvalho, Lais |e verfasserin |4 aut | |
| 700 | 1 | |a Thole, Alessandra |e verfasserin |4 aut | |
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