TY - JOUR
T1 - The Role of Mesenchymal Stem Cells in Treating Diabetic Kidney Disease
T2 - Immunomodulatory Effects and Kidney Regeneration
AU - Hsiao, Po Jen
AU - Kao, Wen Yi
AU - Sung, Li Chin
AU - Lin, Chia Yi
AU - Tsou, Liam Li An
AU - Kao, Yung Hsi
AU - Chou, Chu Lin
AU - Lee, Kung Ta
N1 - Publisher Copyright:
© The author(s).
PY - 2025
Y1 - 2025
N2 - Background: Diabetic kidney disease (DKD), also known as diabetic nephropathy (DN), is characterized by progressive glomerulosclerosis and chronic inflammation. The potential of mesenchymal stem cells (MSCs) in treating DKD could be explored. Methods: In this study, a streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) DKD mouse model was utilized to investigate the renoprotective potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) through immunohistochemical, histopathological, and biochemical analyses. Two separate experiments were conducted to assess the therapeutic efficacy of hUC-MSCs in a DN mouse model. The first experiment determined the optimal dose by assigning the body weight and food intake alterations, serum cytokines and kidney function changes post hUC-MSCs treatment. STZ-induced DKD mice were divided to four groups: DKD control and other three hUC-MSCs treatment groups (low-dose: 3x106, intermediate (middle)-dose: 1x107, and high-dose: 3x107 cells/kg), with intravenous administration at weeks 8, 10, and 12 over 14 weeks. The second experiment evaluated treatment frequency, with mice assigned to hUC-MSCs x1, x2, and x3 groups (3x107 cells/kg) administered at weeks 5, 6, and 7 across 12 weeks, assessing the kidney histology and morphometry changes. Results: In the first experiment, the body weight and food intake showed no significant alterations among the DN and other 3 hUC-MSCs treatment groups. Compared to the DKD control group, only high-dose hUC-MSCs (3x107 cells/kg) treatment group significantly reduced the levels of inflammatory cytokines (IL-1β, and TNF-α) (p <0.05). Additionally, the urine albumin-to-creatinine ratio (UACR) levels in the high-dose hUC-MSCs (3×10⁷ cells/kg) treatment group showed a decreasing trend compared to those in the DN control group (p = 0.06). In the second experiment, the hUC-MSCs x3 treatment group (3×10⁷ cells/kg) significantly alleviated kidney histopathology compared to the DKD group (p <0.05). Conclusion: hUC-MSCs treatment may present a potential avenue for reversing glomerulosclerosis and mitigating inflammation in DKD mice. The long-term therapeutic benefits of MSCs-based treatments in patients with DKD and other kidney diseases could be further investigated.
AB - Background: Diabetic kidney disease (DKD), also known as diabetic nephropathy (DN), is characterized by progressive glomerulosclerosis and chronic inflammation. The potential of mesenchymal stem cells (MSCs) in treating DKD could be explored. Methods: In this study, a streptozotocin (STZ)-induced type 1 diabetes mellitus (T1DM) DKD mouse model was utilized to investigate the renoprotective potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) through immunohistochemical, histopathological, and biochemical analyses. Two separate experiments were conducted to assess the therapeutic efficacy of hUC-MSCs in a DN mouse model. The first experiment determined the optimal dose by assigning the body weight and food intake alterations, serum cytokines and kidney function changes post hUC-MSCs treatment. STZ-induced DKD mice were divided to four groups: DKD control and other three hUC-MSCs treatment groups (low-dose: 3x106, intermediate (middle)-dose: 1x107, and high-dose: 3x107 cells/kg), with intravenous administration at weeks 8, 10, and 12 over 14 weeks. The second experiment evaluated treatment frequency, with mice assigned to hUC-MSCs x1, x2, and x3 groups (3x107 cells/kg) administered at weeks 5, 6, and 7 across 12 weeks, assessing the kidney histology and morphometry changes. Results: In the first experiment, the body weight and food intake showed no significant alterations among the DN and other 3 hUC-MSCs treatment groups. Compared to the DKD control group, only high-dose hUC-MSCs (3x107 cells/kg) treatment group significantly reduced the levels of inflammatory cytokines (IL-1β, and TNF-α) (p <0.05). Additionally, the urine albumin-to-creatinine ratio (UACR) levels in the high-dose hUC-MSCs (3×10⁷ cells/kg) treatment group showed a decreasing trend compared to those in the DN control group (p = 0.06). In the second experiment, the hUC-MSCs x3 treatment group (3×10⁷ cells/kg) significantly alleviated kidney histopathology compared to the DKD group (p <0.05). Conclusion: hUC-MSCs treatment may present a potential avenue for reversing glomerulosclerosis and mitigating inflammation in DKD mice. The long-term therapeutic benefits of MSCs-based treatments in patients with DKD and other kidney diseases could be further investigated.
KW - diabetic kidney disease
KW - diabetic nephropathy
KW - immunomodulation
KW - immunomodulatory effects
KW - kidney regeneration
KW - mesenchymal stem cells
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UR - http://www.scopus.com/inward/citedby.url?scp=86000779757&partnerID=8YFLogxK
U2 - 10.7150/ijms.103806
DO - 10.7150/ijms.103806
M3 - Article
C2 - 40093796
AN - SCOPUS:86000779757
SN - 1449-1907
VL - 22
SP - 1720
EP - 1735
JO - International Journal of Medical Sciences
JF - International Journal of Medical Sciences
IS - 7
ER -
