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

Chang Gung University
Chang Gung Memorial Hospital
National Sun Yat-sen University
Kaohsiung Medical University
National Cheng Kung University
Asia University Taiwan
China Medical University Taichung

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

19 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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

Access to Document

10.1016/j.bj.2023.100613

Cite this

@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

UR - https://www.scopus.com/pages/publications/85187550671

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

Bibliographical note

UN SDGs

Keywords

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