Type 2 Diabetes Alters Mesenchymal Stem Cell Secretome Composition and Angiogenic Properties

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2016 Sep 20

PMID 27641937

Citations 23

Authors

Jonathan Ribot

Guavri Caliaperoumal

Joseph Paquet

Catherine Boisson-Vidal

Herve Petite

Fani Anagnostou

Affiliations

Soon will be listed here.

Abstract

This study aimed at characterizing the impact of type 2 diabetes mellitus (T2DM) on the bone marrow mesenchymal stem cell (BMMSC) secretome and angiogenic properties. BMMSCs from Zucker diabetic fatty rats (ZDF) (a T2DM model) and Zucker LEAN littermates (control) were cultured. The supernatant conditioned media (CM) from BMMSCs of diabetic and control rats were collected and analysed. Compared to results obtained using CM from LEAN-BMMSCs, the bioactive content of ZDF-BMMSC CM (i) differently affects endothelial cell (HUVEC) functions in vitro by inducing increased (3.5-fold; P < 0.01) formation of tubule-like structures and migration of these cells (3-fold; P < 0.001), as well as promotes improved vascular formation in vivo, and (ii) contains different levels of angiogenic factors (e.g. IGF1) and mediators, such as OSTP, CATD, FMOD LTBP1 and LTBP2, which are involved in angiogenesis and/or extracellular matrix composition. Addition of neutralizing antibodies against IGF-1, LTBP1 or LTBP2 in the CM of BMMSCs from diabetic rats decreased its stimulatory effect on HUVEC migration by approximately 60%, 40% or 40%, respectively. These results demonstrate that BMMSCs from T2DM rats have a unique secretome with distinct angiogenic properties and provide new insights into the role of BMMSCs in aberrant angiogenesis in the diabetic milieu.

Citing Articles

Improving the Wound Healing Process: Pivotal role of Mesenchymal stromal/stem Cells and Immune Cells.

Sadeghi M, Moghaddam A, Amiri A, Charoghdoozi K, Mohammadi M, Dehnavi S Stem Cell Rev Rep. 2025; .

PMID: 39921839 DOI: 10.1007/s12015-025-10849-0.

Mesenchymal-Stem-Cell-Based Strategies for Retinal Diseases.

Chen X, Jiang Y, Duan Y, Zhang X, Li X Genes (Basel). 2022; 13(10).

PMID: 36292786 PMC: 9602395. DOI: 10.3390/genes13101901.

Innovative Cell and Platelet Rich Plasma Therapies for Diabetic Foot Ulcer Treatment: The Allogeneic Approach.

Mastrogiacomo M, Nardini M, Collina M, Di Campli C, Filaci G, Cancedda R Front Bioeng Biotechnol. 2022; 10:869408.

PMID: 35586557 PMC: 9108368. DOI: 10.3389/fbioe.2022.869408.

The Fate Status of Stem Cells in Diabetes and its Role in the Occurrence of Diabetic Complications.

Xu J, Zuo C Front Mol Biosci. 2021; 8:745035.

PMID: 34796200 PMC: 8592901. DOI: 10.3389/fmolb.2021.745035.

Diabetes complications and extracellular vesicle therapy.

Soltani S, Mansouri K, Parvaneh S, Thakor A, Pociot F, Yarani R Rev Endocr Metab Disord. 2021; 23(3):357-385.

PMID: 34647239 DOI: 10.1007/s11154-021-09680-y.

References

Ranganath S, Levy O, Inamdar M, Karp J . Harnessing the mesenchymal stem cell secretome for the treatment of cardiovascular disease. Cell Stem Cell. 2012; 10(3):244-58. PMC: 3294273. DOI: 10.1016/j.stem.2012.02.005. View

Park L, Maione A, Smith A, Gerami-Naini B, Iyer L, Mooney D . Genome-wide DNA methylation analysis identifies a metabolic memory profile in patient-derived diabetic foot ulcer fibroblasts. Epigenetics. 2014; 9(10):1339-49. PMC: 4622843. DOI: 10.4161/15592294.2014.967584. View

Abu El-Asrar A, Struyf S, Kangave D, Geboes K, Van Damme J . Chemokines in proliferative diabetic retinopathy and proliferative vitreoretinopathy. Eur Cytokine Netw. 2006; 17(3):155-65. View

Gao Y, Wu F, Zhou J, Yan L, Jurczak M, Lee H . The H19/let-7 double-negative feedback loop contributes to glucose metabolism in muscle cells. Nucleic Acids Res. 2014; 42(22):13799-811. PMC: 4267628. DOI: 10.1093/nar/gku1160. View

Yan J, Tie G, Wang S, Messina K, Didato S, Guo S . Type 2 diabetes restricts multipotency of mesenchymal stem cells and impairs their capacity to augment postischemic neovascularization in db/db mice. J Am Heart Assoc. 2013; 1(6):e002238. PMC: 3540677. DOI: 10.1161/JAHA.112.002238. View

Page P, DeJong J, Bandstra A, Boomsma R . Effect of serum and oxygen concentration on gene expression and secretion of paracrine factors by mesenchymal stem cells. Int J Cell Biol. 2015; 2014:601063. PMC: 4295344. DOI: 10.1155/2014/601063. View

Gruber R, Kandler B, Holzmann P, Vogele-Kadletz M, Losert U, Fischer M . Bone marrow stromal cells can provide a local environment that favors migration and formation of tubular structures of endothelial cells. Tissue Eng. 2005; 11(5-6):896-903. DOI: 10.1089/ten.2005.11.896. View

Kinnaird T, Stabile E, Burnett M, Lee C, Barr S, Fuchs S . Marrow-derived stromal cells express genes encoding a broad spectrum of arteriogenic cytokines and promote in vitro and in vivo arteriogenesis through paracrine mechanisms. Circ Res. 2004; 94(5):678-85. DOI: 10.1161/01.RES.0000118601.37875.AC. View

Reddy M, Zhang E, Natarajan R . Epigenetic mechanisms in diabetic complications and metabolic memory. Diabetologia. 2014; 58(3):443-55. PMC: 4324095. DOI: 10.1007/s00125-014-3462-y. View

10.

Shigematsu S, Yamauchi K, Nakajima K, Iijima S, Aizawa T, Hashizume K . IGF-1 regulates migration and angiogenesis of human endothelial cells. Endocr J. 2002; 46 Suppl:S59-62. DOI: 10.1507/endocrj.46.suppl_s59. View

11.

Tahergorabi Z, Khazaei M . Imbalance of angiogenesis in diabetic complications: the mechanisms. Int J Prev Med. 2012; 3(12):827-38. PMC: 3530300. DOI: 10.4103/2008-7802.104853. View

12.

Salcedo R, Ponce M, Young H, Wasserman K, Ward J, Kleinman H . Human endothelial cells express CCR2 and respond to MCP-1: direct role of MCP-1 in angiogenesis and tumor progression. Blood. 2000; 96(1):34-40. View

13.

Jian J, Zheng Z, Zhang K, Rackohn T, Hsu C, Levin A . Fibromodulin promoted in vitro and in vivo angiogenesis. Biochem Biophys Res Commun. 2013; 436(3):530-535. PMC: 4007216. DOI: 10.1016/j.bbrc.2013.06.005. View

14.

Romaniuk D, Kimsa M, Strzalka-Mrozik B, Kimsa M, Kabiesz A, Romaniuk W . Gene expression of IGF1, IGF1R, and IGFBP3 in epiretinal membranes of patients with proliferative diabetic retinopathy: preliminary study. Mediators Inflamm. 2014; 2013:986217. PMC: 3863537. DOI: 10.1155/2013/986217. View

15.

Rahbarghazi R, Nassiri S, Khazraiinia P, Kajbafzadeh A, Ahmadi S, Mohammadi E . Juxtacrine and paracrine interactions of rat marrow-derived mesenchymal stem cells, muscle-derived satellite cells, and neonatal cardiomyocytes with endothelial cells in angiogenesis dynamics. Stem Cells Dev. 2012; 22(6):855-65. PMC: 3585743. DOI: 10.1089/scd.2012.0377. View

16.

Costa P, Soares R . Neovascularization in diabetes and its complications. Unraveling the angiogenic paradox. Life Sci. 2013; 92(22):1037-45. DOI: 10.1016/j.lfs.2013.04.001. View

17.

Roberts A, Porter K . Cellular and molecular mechanisms of endothelial dysfunction in diabetes. Diab Vasc Dis Res. 2013; 10(6):472-82. DOI: 10.1177/1479164113500680. View

18.

Bach L . Endothelial cells and the IGF system. J Mol Endocrinol. 2014; 54(1):R1-13. DOI: 10.1530/JME-14-0215. View

19.

Gealekman O, Brodsky S, Zhang F, Chander P, Friedli C, Nasjletti A . Endothelial dysfunction as a modifier of angiogenic response in Zucker diabetic fat rat: amelioration with Ebselen. Kidney Int. 2004; 66(6):2337-47. DOI: 10.1111/j.1523-1755.2004.66035.x. View

20.

Bronckaers A, Hilkens P, Martens W, Gervois P, Ratajczak J, Struys T . Mesenchymal stem/stromal cells as a pharmacological and therapeutic approach to accelerate angiogenesis. Pharmacol Ther. 2014; 143(2):181-96. DOI: 10.1016/j.pharmthera.2014.02.013. View