Proteomic Analysis of Human Mesenchymal Stromal Cell Secretomes: a Systematic Comparison of the Angiogenic Potential

Overview

Journal NPJ Regen Med

Date 2019 Apr 25

PMID 31016031

Citations 94

Authors

Debora Kehl

Melanie Generali

Anna Mallone

Manfred Heller

Anne-Christine Uldry

Phil Cheng

Benjamin Gantenbein

Simon P Hoerstrup

Benedikt Weber

Affiliations

Soon will be listed here.

Abstract

Human mesenchymal stromal cell (hMSC) secretomes have shown to influence the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair. The angiogenic potential is of particular interest for the treatment of ischemic diseases. Interestingly, hMSC secretomes isolated from different tissue sources have shown dissimilarities with respect to their angiogenic profile. This study compares angiogenesis of hMSC secretomes from adipose tissue (hADSCs), bone marrow (hBMSCs), and umbilical cord Wharton's jelly (hWJSCs). hMSC secretomes were obtained under xenofree conditions and analyzed by liquid chromatography tandem mass spectrometry (LC/MS-MS). Biological processes related to angiogenesis were found to be enriched in the proteomic profile of hMSC secretomes. hWJSC secretomes revealed a more complete angiogenic network with higher concentrations of angiogenesis related proteins, followed by hBMSC secretomes. hADSC secretomes lacked central angiogenic proteins and expressed most detected proteins to a significantly lower level. In vivo all secretomes induced vascularization of subcutaneously implanted Matrigel plugs in mice. Differences in secretome composition were functionally analyzed with monocyte and endothelial cell (EC) in vitro co-culture experiments using vi-SNE based multidimensional flow cytometry data analysis. Functional responses between hBMSC and hWJSC secretomes were comparable, with significantly higher migration of CD14 CD16 monocytes and enhanced macrophage differentiation compared with hADSC secretomes. Both secretomes also induced a more profound pro-angiogenic phenotype of ECs. These results suggest hWJSCs secretome as the most potent hMSC source for inflammation-mediated angiogenesis induction, while the potency of hADSC secretomes was lowest. This systematic analysis may have implication on the selection of hMSCs for future clinical studies.

Citing Articles

Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing.

Hodgson-Garms M, Moore M, Martino M, Kelly K, Frith J NPJ Regen Med. 2025; 10(1):7.

PMID: 39905050 PMC: 11794695. DOI: 10.1038/s41536-024-00382-y.

Standardization to Characterize the Complexity of Vessel Network Using the Aortic Ring Model.

Wolint P, Hofmann S, von Atzigen J, Boni R, Miescher I, Giovanoli P Int J Mol Sci. 2025; 26(1.

PMID: 39796147 PMC: 11719671. DOI: 10.3390/ijms26010291.

Anti-necroptotic effects of human Wharton's jelly-derived mesenchymal stem cells in skeletal muscle cell death model via secretion of GRO-α.

Park S, Kwon S, Kim S, Jeong J, Kim M, Choi S PLoS One. 2024; 19(12):e0313693.

PMID: 39621655 PMC: 11611217. DOI: 10.1371/journal.pone.0313693.

Proteomic analysis of human Wharton's jelly mesenchymal stem/stromal cells and human amniotic epithelial stem cells: a comparison of therapeutic potential.

Ge Z, Qiu C, Zhou J, Yang Z, Jiang T, Yuan W Sci Rep. 2024; 14(1):28061.

PMID: 39543366 PMC: 11564572. DOI: 10.1038/s41598-024-79063-1.

Epicardial transplantation of antioxidant polyurethane scaffold based human amniotic epithelial stem cell patch for myocardial infarction treatment.

Li J, Yao Y, Zhou J, Yang Z, Qiu C, Lu Y Nat Commun. 2024; 15(1):9105.

PMID: 39438477 PMC: 11496666. DOI: 10.1038/s41467-024-53531-8.

References

Moldovan N . Role of monocytes and macrophages in adult angiogenesis: a light at the tunnel's end. J Hematother Stem Cell Res. 2002; 11(2):179-94. DOI: 10.1089/152581602753658394. View

Ranganath R . Harnessing the developmental potential of nucellar cells: barriers and opportunities. Trends Biotechnol. 2004; 22(10):504-10. DOI: 10.1016/j.tibtech.2004.08.010. View

Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D . Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006; 8(4):315-7. DOI: 10.1080/14653240600855905. View

Dominguez-Sola D, Ying C, Grandori C, Ruggiero L, Chen B, Li M . Non-transcriptional control of DNA replication by c-Myc. Nature. 2007; 448(7152):445-51. DOI: 10.1038/nature05953. View

dAdda di Fagagna F . Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer. 2008; 8(7):512-22. DOI: 10.1038/nrc2440. View

Gnecchi M, He H, Melo L, Noiseaux N, Morello F, de Boer R . Early beneficial effects of bone marrow-derived mesenchymal stem cells overexpressing Akt on cardiac metabolism after myocardial infarction. Stem Cells. 2009; 27(4):971-9. PMC: 2873075. DOI: 10.1002/stem.12. View

Bieback K, Hecker A, Kocaomer A, Lannert H, Schallmoser K, Strunk D . Human alternatives to fetal bovine serum for the expansion of mesenchymal stromal cells from bone marrow. Stem Cells. 2009; 27(9):2331-41. DOI: 10.1002/stem.139. View

Lee R, Pulin A, Seo M, Kota D, Ylostalo J, Larson B . Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009; 5(1):54-63. PMC: 4154377. DOI: 10.1016/j.stem.2009.05.003. View

Baraniak P, McDevitt T . Stem cell paracrine actions and tissue regeneration. Regen Med. 2009; 5(1):121-43. PMC: 2833273. DOI: 10.2217/rme.09.74. View

10.

Hsieh J, Fu Y, Chang S, Tsuang Y, Wang H . Functional module analysis reveals differential osteogenic and stemness potentials in human mesenchymal stem cells from bone marrow and Wharton's jelly of umbilical cord. Stem Cells Dev. 2010; 19(12):1895-910. DOI: 10.1089/scd.2009.0485. View

11.

Svatek R, Shah J, Xing J, Chang D, Lin J, McConkey D . A multiplexed, particle-based flow cytometric assay identified plasma matrix metalloproteinase-7 to be associated with cancer-related death among patients with bladder cancer. Cancer. 2010; 116(19):4513-9. DOI: 10.1002/cncr.25401. View

12.

Von Bahr L, Sundberg B, Lonnies L, Sander B, Karbach H, Hagglund H . Long-term complications, immunologic effects, and role of passage for outcome in mesenchymal stromal cell therapy. Biol Blood Marrow Transplant. 2011; 18(4):557-64. DOI: 10.1016/j.bbmt.2011.07.023. View

13.

Hsiao S, Asgari A, Lokmic Z, Sinclair R, Dusting G, Lim S . Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue. Stem Cells Dev. 2011; 21(12):2189-203. PMC: 3411362. DOI: 10.1089/scd.2011.0674. View

14.

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

15.

Lee T, Bhang S, Yang H, La W, Yoon H, Shin J . Enhancement of long-term angiogenic efficacy of adipose stem cells by delivery of FGF2. Microvasc Res. 2012; 84(1):1-8. DOI: 10.1016/j.mvr.2012.04.004. View

16.

Brown K, Formolo C, Seol H, Marathi R, Duguez S, An E . Advances in the proteomic investigation of the cell secretome. Expert Rev Proteomics. 2012; 9(3):337-45. PMC: 3500636. DOI: 10.1586/epr.12.21. View

17.

Amir E, Davis K, Tadmor M, Simonds E, Levine J, Bendall S . viSNE enables visualization of high dimensional single-cell data and reveals phenotypic heterogeneity of leukemia. Nat Biotechnol. 2013; 31(6):545-52. PMC: 4076922. DOI: 10.1038/nbt.2594. View

18.

Hsieh J, Wang H, Chang S, Liao K, Lee I, Lin W . Mesenchymal stem cells from human umbilical cord express preferentially secreted factors related to neuroprotection, neurogenesis, and angiogenesis. PLoS One. 2013; 8(8):e72604. PMC: 3749979. DOI: 10.1371/journal.pone.0072604. View

19.

Murphy M, Moncivais K, Caplan A . Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013; 45:e54. PMC: 3849579. DOI: 10.1038/emm.2013.94. View

20.

Zhou B, Xu Y, Guo S, Xu Y, Wang Y, Zhu F . The effect of conditioned media of adipose-derived stem cells on wound healing after ablative fractional carbon dioxide laser resurfacing. Biomed Res Int. 2014; 2013:519126. PMC: 3867954. DOI: 10.1155/2013/519126. View