Transplantation of Human Amniotic Mesenchymal Stem Cells Up-Regulates Angiogenic Factor Expression to Attenuate Diabetic Kidney Disease in Rats

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2023 Feb 14

PMID 36785675

Authors

Yu Ni

Yuqin Chen

Xuheng Jiang

Tao Pu

Ling Zhang

Shaobin Li

Linhong Hu

Bing Bai

Tingting Hu

Limei Yu

Yibin Yang

Affiliations

Soon will be listed here.

Abstract

Background And Aims: Diabetic kidney disease (DKD) is a prevalent and intractable microvascular complication of diabetes mellitus (DM), the process of which is closely related to abnormal expression of angiogenesis-regulating factors (ARFs). Stem cell transplantation might be a novel strategy for treating DKD. This study aims to explore the effect of transplantation of human amniotic mesenchymal stem cells (hAMSCs) on renal microangiopathy in a type 1 DKD rat model (T1DRM).

Methods: Seventy-two rats were randomly divided into three groups, including normal control group, DKD group, and hAMSCs transplantation group. T1DRM was established using a rat tail vein injection of streptozotocin (STZ) (55 mg/kg). hAMSCs were obtained from placental amniotic membranes during cesarean delivery and transplanted at 3 and 4 weeks through penile veins. At 6, 8, and 12 weeks following transplantation, blood glucose levels, renal function, pathological kidney alterations, and the expressions of ARFs' mRNA and protein were analyzed.

Results: In T1DRM, transplanted hAMSCs that were homed at the injured site of kidneys increased ARFs' expression and decreased blood glucose levels. Compared to the DKD group, the levels of 24-h urinary protein, serum creatinine, urea, and kidney injury molecule-1 (KIM-1) were reduced in hAMSCs transplantation group. In terms of renal pathology such as the degree of basement membrane thickening, hAMSCs transplantation was also less severe than the DKD group, thereby alleviating kidney injury.

Conclusion: hAMSCs transplantation might ameliorate STZ-induced chronic kidney injury through increasing ARFs' expression in kidneys and lowering blood glucose levels.

Citing Articles

Mesenchymal Stem Cell Therapy: Therapeutic Opportunities and Challenges for Diabetic Kidney Disease.

Cheng J, Zhang C Int J Mol Sci. 2024; 25(19).

PMID: 39408867 PMC: 11477055. DOI: 10.3390/ijms251910540.

The therapeutic effect of mesenchymal stem cells in diabetic kidney disease.

Habiba U, Khan N, Greene D, Shamim S, Umer A J Mol Med (Berl). 2024; 102(4):537-570.

PMID: 38418620 PMC: 10963471. DOI: 10.1007/s00109-024-02432-w.

References

Gowd V, Kang Q, Wang Q, Wang Q, Chen F, Cheng K . Resveratrol: Evidence for Its Nephroprotective Effect in Diabetic Nephropathy. Adv Nutr. 2020; 11(6):1555-1568. PMC: 7666903. DOI: 10.1093/advances/nmaa075. View

Ebaid H, Bashandy S, Abdel-Mageed A, Al-Tamimi J, Hassan I, Alhazza I . Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress. Nutr Metab (Lond). 2020; 17:6. PMC: 6961249. DOI: 10.1186/s12986-019-0419-7. View

Nakagawa T, Kosugi T, Haneda M, Rivard C, Long D . Abnormal angiogenesis in diabetic nephropathy. Diabetes. 2009; 58(7):1471-8. PMC: 2699857. DOI: 10.2337/db09-0119. View

Bai Y, Wang J, He Z, Yang M, Li L, Jiang H . Mesenchymal Stem Cells Reverse Diabetic Nephropathy Disease via Lipoxin A4 by Targeting Transforming Growth Factor β (TGF-β)/smad Pathway and Pro-Inflammatory Cytokines. Med Sci Monit. 2019; 25:3069-3076. PMC: 6500104. DOI: 10.12659/MSM.914860. View

Liu Y, Tang S . Recent Progress in Stem Cell Therapy for Diabetic Nephropathy. Kidney Dis (Basel). 2016; 2(1):20-7. PMC: 4946257. DOI: 10.1159/000441913. View

Li S, Zou H, Gong M, Chen Y, Yan X, Yu L . Angiopoietin-1 Promotes the Integrity of Neovascularization in the Subcutaneous Matrigel of Type 1 Diabetic Rats. Biomed Res Int. 2019; 2019:2016972. PMC: 6343146. DOI: 10.1155/2019/2016972. View

Zang L, Hao H, Liu J, Li Y, Han W, Mu Y . Mesenchymal stem cell therapy in type 2 diabetes mellitus. Diabetol Metab Syndr. 2017; 9:36. PMC: 5433043. DOI: 10.1186/s13098-017-0233-1. View

Liu Q, Huang Q, Wu H, Zuo G, Gu H, Deng K . Characteristics and Therapeutic Potential of Human Amnion-Derived Stem Cells. Int J Mol Sci. 2021; 22(2). PMC: 7835733. DOI: 10.3390/ijms22020970. View

de Mayo T, Conget P, Becerra-Bayona S, Sossa C, Galvis V, Arango-Rodriguez M . The role of bone marrow mesenchymal stromal cell derivatives in skin wound healing in diabetic mice. PLoS One. 2017; 12(6):e0177533. PMC: 5464535. DOI: 10.1371/journal.pone.0177533. View

10.

Daios S, Kaiafa G, Pilalas D, Nakou I, Kanellos I, Kirdas K . Endothelial Dysfunction and Platelet Hyperaggregation in Type 2 Diabetes Mellitus: The Era of Novel Anti-diabetic Agents. Curr Med Chem. 2020; 28(20):3935-3963. DOI: 10.2174/0929867327666201009143816. View

11.

De Vriese A, Tilton R, Elger M, Stephan C, Kriz W, Lameire N . Antibodies against vascular endothelial growth factor improve early renal dysfunction in experimental diabetes. J Am Soc Nephrol. 2001; 12(5):993-1000. DOI: 10.1681/ASN.V125993. View

12.

Shukla R, Pandey N, Banerjee S, Tripathi Y . Effect of extract of Pueraria tuberosa on expression of hypoxia inducible factor-1α and vascular endothelial growth factor in kidney of diabetic rats. Biomed Pharmacother. 2017; 93:276-285. DOI: 10.1016/j.biopha.2017.06.045. View

13.

Xiang E, Han B, Zhang Q, Rao W, Wang Z, Chang C . Human umbilical cord-derived mesenchymal stem cells prevent the progression of early diabetic nephropathy through inhibiting inflammation and fibrosis. Stem Cell Res Ther. 2020; 11(1):336. PMC: 7397631. DOI: 10.1186/s13287-020-01852-y. View

14.

Zhang Y, Liu J, Zou T, Qi Y, Yi B, Dissanayaka W . DPSCs treated by TGF-β1 regulate angiogenic sprouting of three-dimensionally co-cultured HUVECs and DPSCs through VEGF-Ang-Tie2 signaling. Stem Cell Res Ther. 2021; 12(1):281. PMC: 8112067. DOI: 10.1186/s13287-021-02349-y. View

15.

Zhang Y, Hao Z, Wang P, Xia Y, Wu J, Xia D . Exosomes from human umbilical cord mesenchymal stem cells enhance fracture healing through HIF-1α-mediated promotion of angiogenesis in a rat model of stabilized fracture. Cell Prolif. 2019; 52(2):e12570. PMC: 6496165. DOI: 10.1111/cpr.12570. View

16.

An Y, Liu W, Xue P, Ma Y, Zhang L, Zhu B . Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion. Cell Death Dis. 2018; 9(2):58. PMC: 5833357. DOI: 10.1038/s41419-017-0082-8. View

17.

Hou N, Huang N, Han F, Zhao J, Liu X, Sun X . Protective effects of adiponectin on uncoupling of glomerular VEGF-NO axis in early streptozotocin-induced type 2 diabetic rats. Int Urol Nephrol. 2014; 46(10):2045-51. DOI: 10.1007/s11255-014-0807-x. View

18.

Zou X, Gu D, Xing X, Cheng Z, Gong D, Zhang G . Human mesenchymal stromal cell-derived extracellular vesicles alleviate renal ischemic reperfusion injury and enhance angiogenesis in rats. Am J Transl Res. 2016; 8(10):4289-4299. PMC: 5095321. View

19.

Yan Z, Luo Y, Liu N . Blockade of angiopoietin-2/Tie2 signaling pathway specifically promotes inflammation-induced angiogenesis in mouse cornea. Int J Ophthalmol. 2017; 10(8):1187-1194. PMC: 5554834. DOI: 10.18240/ijo.2017.08.01. View

20.

Nakagawa T, Sato W, Kosugi T, Johnson R . Uncoupling of VEGF with endothelial NO as a potential mechanism for abnormal angiogenesis in the diabetic nephropathy. J Diabetes Res. 2014; 2013:184539. PMC: 3872226. DOI: 10.1155/2013/184539. View