Senescent mesenchymal stem/stromal cells and restoring their cellular functions

Table 2 Summary of secretome alteration analysis studies of senescent mesenchymal stem cells

Ref.	Species	Tissue sources	Classification	Cells	Groups	Differentially expressed proteins	Identification of targets
Kizilay et al[56], 2017	Human	Subcutaneous and pericardial adipose tissue	R&D Systems Human Cytokine Array; multispot electrochemiluminescence immunoassay V-Plex Pro inflammatory Panel	CD44, CD73, CD105, and CD90 expression was more than 95%; CD45, CD34, CD19, CD14, and HLA-DR expression was less than 5%; differentiation capacity toward three lineages was assessed	E-MSCs: MSCs from elderly ATH patients (> 65 yr old); A-MSCs: MSCs from adult ATH patients (< 65 yr old)	The expression of IL-6, IL-8/CXCL8, MCP-1/CCL2, MIF, IFN-g, IL12p70, IL-13, IL-2, and IL-4 was elevated in E-MSCs relative to A-MSCs	Neutralization of IL-6, IL-8/CXCL8, and MCP-1/CCL2 significantly improved the E-MSCs’ immunomodulatory function
Infante et al[57], 2018	Human	Bone marrow	Semi-quantitative antibody arrays; liquid chromatography-mass spectrometry (LC-MS): Version 4.0.4265.42984, Nonlinear Dynamics	Obtained from Lonza commercially; passages 3-4	Ctrl-hMSCs: Incubated with dimethyl sulfoxide alone; PreA-hMSCs: Treated with the HIV protease inhibitor (tipranavir) every other day until passage 11	A dysregulation in the secretion levels of 42 proteins was detected by antibody arrays; 44 were detected by LS-MS in preA-hMSCs; most of them were overexpressed in preA-hMSCs, in comparison with ctrl-hMSCs	IGFBP7 is essential for hMSCs viability during early osteogenic diferentiation
Madonna et al[58], 2019	Mouse	Peri-epididymal visceral adipose tissue from 1-yr-old male C57BL/6 mice	Two-dimensional gel electrophoresis (2DE); matrix-assisted laser desorption/ionization time-of-fight mass spectrometry	The expression of CD45, CD34, CD133, ASMA, Desmin, CD105, CD73, CD90, CD79, and CD160 was analyzed by flow cytometry	Mock AT-MSCs: Mock-transduced AT-MSCs; rTMAT-MSCs: Rejuvenated by TERT and the anti-apoptotic transcription factor myocardin overexpression	113 protein spots were picked up and identified from the whole CM and exosome-enriched fraction in rTMAT-MSCs	Two novel candidates supporting angiogenesis in the whole CM of rTMAT-MSCs: MMP2 and its inhibitor TIMP2

hMSC: Human mesenchymal stem cells; MSC: Mesenchymal stem cells; TERT: Telomerase reverse transcriptase; MMP2: Matrix metalloproteinase-2; CM: Conditioned medium; LC-MS: Liquid chromatography-mass spectrometry.