Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat

Chih‐Chao C. Yang; Yi Ling Chen; Pei Hsun Sung; John Y. Chiang; Chih Hung Chen; Yi Chen Li; Hon Kan Yip

doi:10.1016/j.bj.2023.100613

Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat

Chih‐Chao C. Yang, Yi Ling Chen, Pei Hsun Sung, John Y. Chiang, Chih Hung Chen, Yi Chen Li^*, Hon Kan Yip^*

^*Corresponding author for this work

School of Medicine

Research output: Contribution to journal › Journal Article › peer-review

3 Scopus citations

Abstract

BACKGROUND: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats.

METHODS: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 10 5/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 10 6/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction.

RESULTS: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p < 0.0001). The protein levels of inflammation (NF-κB/FNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized protein/p22-phox)/apoptosis (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax)/fibrosis (TGF-β/Smad 3)/mitochondrial/DNA-damaged (p-DRP1/γ-H2AX) biomarkers revealed a similar manner of creatinine level among the groups (all p < 0.0001). Kidney injury score/fibrotic area/oxidative-stress score (8-OHdG) and cellular levels of kidney-damaged biomarkers (KIM-1/γ-H2AX) showed a unanimous manner. In contrast, the cellular expressions of podocyte components (ZO-1/synaptopodin) revealed an antithetical manner of creatinine among the groups (all p < 0.0001).

CONCLUSION: Combined ADMSCs-EMPA was superior to just one therapy for protecting kidney function and ultra-structural integrity in DKD rodents.

Original language	English
Article number	100613
Pages (from-to)	100613
Journal	Biomedical Journal
Volume	47
Issue number	2
DOIs	https://doi.org/10.1016/j.bj.2023.100613
State	Published - 04 2024

Bibliographical note

Keywords

Diabetic kidney disease
Inflammation
Oxidative stress
Renal function
Rats
Glucosides/pharmacology
Male
Rats, Sprague-Dawley
Mesenchymal Stem Cell Transplantation/methods
Oxidative Stress/drug effects
Kidney/drug effects
Animals
Mesenchymal Stem Cells/drug effects
Diabetic Nephropathies/drug therapy
Adipose Tissue/drug effects
Benzhydryl Compounds/pharmacology

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10.1016/j.bj.2023.100613

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@article{d223e42edd434a2d97e7347a77fcf1a9,

title = "Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat",

abstract = "BACKGROUND: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats.METHODS: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 10 5/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 10 6/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. RESULTS: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p < 0.0001). The protein levels of inflammation (NF-κB/FNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized protein/p22-phox)/apoptosis (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax)/fibrosis (TGF-β/Smad 3)/mitochondrial/DNA-damaged (p-DRP1/γ-H2AX) biomarkers revealed a similar manner of creatinine level among the groups (all p < 0.0001). Kidney injury score/fibrotic area/oxidative-stress score (8-OHdG) and cellular levels of kidney-damaged biomarkers (KIM-1/γ-H2AX) showed a unanimous manner. In contrast, the cellular expressions of podocyte components (ZO-1/synaptopodin) revealed an antithetical manner of creatinine among the groups (all p < 0.0001).CONCLUSION: Combined ADMSCs-EMPA was superior to just one therapy for protecting kidney function and ultra-structural integrity in DKD rodents.",

keywords = "Diabetic kidney disease, Inflammation, Oxidative stress, Renal function, Rats, Glucosides/pharmacology, Male, Rats, Sprague-Dawley, Mesenchymal Stem Cell Transplantation/methods, Oxidative Stress/drug effects, Kidney/drug effects, Animals, Mesenchymal Stem Cells/drug effects, Diabetic Nephropathies/drug therapy, Adipose Tissue/drug effects, Benzhydryl Compounds/pharmacology",

author = "Yang, {Chih‐Chao C.} and Chen, {Yi Ling} and Sung, {Pei Hsun} and Chiang, {John Y.} and Chen, {Chih Hung} and Li, {Yi Chen} and Yip, {Hon Kan}",

note = "{\textcopyright} 2023 The Authors. Published by Elsevier B.V. on behalf of Chang Gung University. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).",

year = "2024",

month = apr,

doi = "10.1016/j.bj.2023.100613",

language = "英语",

volume = "47",

pages = "100613",

journal = "Biomedical Journal",

issn = "2319-4170",

publisher = "Elsevier B.V.",

number = "2",

}

Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat. / Yang, Chih‐Chao C.; Chen, Yi Ling; Sung, Pei Hsun et al.
In: Biomedical Journal, Vol. 47, No. 2, 100613, 04.2024, p. 100613.

Research output: Contribution to journal › Journal Article › peer-review

TY - JOUR

T1 - Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat

AU - Yang, Chih‐Chao C.

AU - Chen, Yi Ling

AU - Sung, Pei Hsun

AU - Chiang, John Y.

AU - Chen, Chih Hung

AU - Li, Yi Chen

AU - Yip, Hon Kan

PY - 2024/4

Y1 - 2024/4

N2 - BACKGROUND: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats.METHODS: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 10 5/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 10 6/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. RESULTS: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p < 0.0001). The protein levels of inflammation (NF-κB/FNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized protein/p22-phox)/apoptosis (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax)/fibrosis (TGF-β/Smad 3)/mitochondrial/DNA-damaged (p-DRP1/γ-H2AX) biomarkers revealed a similar manner of creatinine level among the groups (all p < 0.0001). Kidney injury score/fibrotic area/oxidative-stress score (8-OHdG) and cellular levels of kidney-damaged biomarkers (KIM-1/γ-H2AX) showed a unanimous manner. In contrast, the cellular expressions of podocyte components (ZO-1/synaptopodin) revealed an antithetical manner of creatinine among the groups (all p < 0.0001).CONCLUSION: Combined ADMSCs-EMPA was superior to just one therapy for protecting kidney function and ultra-structural integrity in DKD rodents.

AB - BACKGROUND: Diabetic kidney disease (DKD) is one of the most significant public health burdens worldwide. This study explored the renal protections of combined adipose-derived mesenchymal stem cells (ADMSCs) and empagliflozin (EMPA) in DKD rats.METHODS: Adult-male-SD rats were equally allocated into group 1 (sham-operated-control), group 2 (DKD), group 3 (DKD + EMPA/20 mg/kg/day since day-14 after CKD-induction), group 4 [DKD + ADMSCs (6.0 × 10 5/intrarenal-arterial-injection/post-day-28, followed by 1.2 × 10 6/intravenous injection post-days 35 and 42 after CKD-induction, i.e., defined as repeated administration)] and group 5 (DKD + ADMSCs + EMPA) and kidney was harvested post-day-60 CKD-induction. RESULTS: The result showed that the blood sugar and circulatory levels of BUN/creatinine and the ratio of urine protein/creatinine at day 60 were greatly increased in group 2 as compared the SC (i.e., group 1), significantly increased in groups 3 and 4 than in groups 5, but these parameters showed the similar manner in groups 3 and 4, except for blood sugar that was significantly lower in group 3 than in group 4 (all p < 0.0001). The protein levels of inflammation (NF-κB/FNF-α/MMP-9)/oxidative-stress (NOX-1/NOX-2/oxidized protein/p22-phox)/apoptosis (cleaved-caspase-3/cleaved-PARP/mitochondrial-Bax)/fibrosis (TGF-β/Smad 3)/mitochondrial/DNA-damaged (p-DRP1/γ-H2AX) biomarkers revealed a similar manner of creatinine level among the groups (all p < 0.0001). Kidney injury score/fibrotic area/oxidative-stress score (8-OHdG) and cellular levels of kidney-damaged biomarkers (KIM-1/γ-H2AX) showed a unanimous manner. In contrast, the cellular expressions of podocyte components (ZO-1/synaptopodin) revealed an antithetical manner of creatinine among the groups (all p < 0.0001).CONCLUSION: Combined ADMSCs-EMPA was superior to just one therapy for protecting kidney function and ultra-structural integrity in DKD rodents.

KW - Diabetic kidney disease

KW - Inflammation

KW - Oxidative stress

KW - Renal function

KW - Rats

KW - Glucosides/pharmacology

KW - Male

KW - Rats, Sprague-Dawley

KW - Mesenchymal Stem Cell Transplantation/methods

KW - Oxidative Stress/drug effects

KW - Kidney/drug effects

KW - Animals

KW - Mesenchymal Stem Cells/drug effects

KW - Diabetic Nephropathies/drug therapy

KW - Adipose Tissue/drug effects

KW - Benzhydryl Compounds/pharmacology

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U2 - 10.1016/j.bj.2023.100613

DO - 10.1016/j.bj.2023.100613

M3 - 文章

C2 - 37355087

AN - SCOPUS:85187550671

SN - 2319-4170

VL - 47

SP - 100613

JO - Biomedical Journal

JF - Biomedical Journal

IS - 2

M1 - 100613

ER -

Repeated administration of adipose-derived mesenchymal stem cells added on beneficial effects of empagliflozin on protecting renal function in diabetic kidney disease rat

Abstract

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Keywords

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