Bone Marrow Mesenchymal Stem Cell-derived Exosomal MicroRNA-99b-5p Promotes Cell Growth of High Glucose-treated Human Umbilical Vein Endothelial Cells by Modulating THAP Domain Containing 2 Expression

Overview

Journal Curr Stem Cell Res Ther

Publisher Bentham Science Publishers

Specialties Cell Biology
Pharmacology

Date 2024 Feb 15

PMID 38357906

Authors

Hongru Ruan

Hui Shi

Wenkang Luan

Sida Pan

Affiliations

Soon will be listed here.

Abstract

Introduction: Bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) may function as novel candidates for treating diabetic wounds due to their ability to promote angiogenesis.

Materials And Methods: This study investigated the effects of BMSC-exos on the growth and metastasis of human umbilical vein endothelial cells (HUVECs) treated with high glucose (HG). The exosomes were separated from BMSCs and identified. The cell phenotype was detected by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and 5-ethynyl-2'-deoxyuridine, wound healing, and transwell assays, while the number of tubes was measured tube formation assay.

Result: The RNA and protein expression levels were studied using reverse transcription-quantitative polymerase chain reaction and western blotting, whereas integration of microRNA-99b-5p (miR-99b-5p) with THAP domain containing 2 (THAP2) was confirmed dual-luciferase reporter and RNA pull-down assays. Results of transmission electron microscopy, nanoparticle tracking analysis, and laser scanning confocal microscopy revealed that exosomes were successfully separated from BMSCs and endocytosed into the cytoplasm by HUVECs. Similarly, BMSC-exos were found to promote the growth of HG-treated HUVECs, while their growth was inhibited by suppressing miR-99b-5p. THAP2 was found to bind to miR-99b-5p, where THAP2 inhibition reversed the miR-99b-5p-induced effects on cell growth, migration, and tube numbers.

Conclusion: In conclusion, miR-99b-5p in BMSC-exo protects HUVECs by negatively regulating THAP2 expression.

References

Bommer C, Sagalova V, Heesemann E, Manne-Goehler J, Atun R, Barnighausen T . Global Economic Burden of Diabetes in Adults: Projections From 2015 to 2030. Diabetes Care. 2018; 41(5):963-970. DOI: 10.2337/dc17-1962. View

Vaz de Castro P, Bitencourt L, Campos J, Fischer B, Brito S, Santana Soares B . Nephrogenic diabetes insipidus: a comprehensive overview. J Pediatr Endocrinol Metab. 2022; 35(4):421-434. DOI: 10.1515/jpem-2021-0566. View

Morris A . New test for diabetes insipidus. Nat Rev Endocrinol. 2019; 15(10):564-565. DOI: 10.1038/s41574-019-0247-x. View

Maranda E, Rodriguez-Menocal L, Badiavas E . Role of Mesenchymal Stem Cells in Dermal Repair in Burns and Diabetic Wounds. Curr Stem Cell Res Ther. 2016; 12(1):61-70. DOI: 10.2174/1574888x11666160714115926. View

Cho H, Blatchley M, Duh E, Gerecht S . Acellular and cellular approaches to improve diabetic wound healing. Adv Drug Deliv Rev. 2018; 146:267-288. DOI: 10.1016/j.addr.2018.07.019. View

Holl J, Kowalewski C, Zimek Z, Fiedor P, Kaminski A, Oldak T . Chronic Diabetic Wounds and Their Treatment with Skin Substitutes. Cells. 2021; 10(3). PMC: 8001234. DOI: 10.3390/cells10030655. View

Sen C . Human Wound and Its Burden: Updated 2020 Compendium of Estimates. Adv Wound Care (New Rochelle). 2021; 10(5):281-292. PMC: 8024242. DOI: 10.1089/wound.2021.0026. View

Ko K, Sculean A, Graves D . Diabetic wound healing in soft and hard oral tissues. Transl Res. 2021; 236:72-86. PMC: 8554709. DOI: 10.1016/j.trsl.2021.05.001. View

Han G, Ceilley R . Chronic Wound Healing: A Review of Current Management and Treatments. Adv Ther. 2017; 34(3):599-610. PMC: 5350204. DOI: 10.1007/s12325-017-0478-y. View

10.

Yan C, Chen J, Wang C, Yuan M, Kang Y, Wu Z . Milk exosomes-mediated miR-31-5p delivery accelerates diabetic wound healing through promoting angiogenesis. Drug Deliv. 2022; 29(1):214-228. PMC: 8741248. DOI: 10.1080/10717544.2021.2023699. View

11.

Chen X, Jiang W, Liu Y, Ma Z, Dai J . Anti-inflammatory action of geniposide promotes wound healing in diabetic rats. Pharm Biol. 2022; 60(1):294-299. PMC: 8823683. DOI: 10.1080/13880209.2022.2030760. View

12.

Kunkemoeller B, Kyriakides T . Redox Signaling in Diabetic Wound Healing Regulates Extracellular Matrix Deposition. Antioxid Redox Signal. 2017; 27(12):823-838. PMC: 5647483. DOI: 10.1089/ars.2017.7263. View

13.

Li Y, Lin S, Xiong S, Xie Q . Recombinant Expression of Human IL-33 Protein and Its Effect on Skin Wound Healing in Diabetic Mice. Bioengineering (Basel). 2022; 9(12). PMC: 9774120. DOI: 10.3390/bioengineering9120734. View

14.

Shu X, Shu S, Tang S, Yang L, Liu D, Li K . Efficiency of stem cell based therapy in the treatment of diabetic foot ulcer: a meta-analysis. Endocr J. 2018; 65(4):403-413. DOI: 10.1507/endocrj.EJ17-0424. View

15.

Lopes L, Setia O, Aurshina A, Liu S, Hu H, Isaji T . Stem cell therapy for diabetic foot ulcers: a review of preclinical and clinical research. Stem Cell Res Ther. 2018; 9(1):188. PMC: 6042254. DOI: 10.1186/s13287-018-0938-6. View

16.

FRIEDENSTEIN A, PETRAKOVA K, Kurolesova A, Frolova G . Heterotopic of bone marrow. Analysis of precursor cells for osteogenic and hematopoietic tissues. Transplantation. 1968; 6(2):230-47. View

17.

Pixley J . Mesenchymal stem cells to treat type 1 diabetes. Biochim Biophys Acta Mol Basis Dis. 2018; 1866(4):165315. DOI: 10.1016/j.bbadis.2018.10.033. View

18.

Li H, Fu X . Mechanisms of action of mesenchymal stem cells in cutaneous wound repair and regeneration. Cell Tissue Res. 2012; 348(3):371-7. DOI: 10.1007/s00441-012-1393-9. View

19.

Gnecchi M, Zhang Z, Ni A, Dzau V . Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 2008; 103(11):1204-19. PMC: 2667788. DOI: 10.1161/CIRCRESAHA.108.176826. View

20.

Poltavtseva R, Poltavtsev A, Lutsenko G, Svirshchevskaya E . Myths, reality and future of mesenchymal stem cell therapy. Cell Tissue Res. 2018; 375(3):563-574. DOI: 10.1007/s00441-018-2961-4. View