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Keywords: drug discovery, extracellular matrix, regenerative medicine, secretome, target discovery, therapeutic potential Abbreviations SMA alphasmooth muscle actin GT GammaGlutamyl Transferase 3D three dimensional A549 adenocarcinomic human alveolar basal epithelial cells ADMSC adipose tissuederived mesenchymal stem cell ADSC adiposederived stem cell AGF angiogenic growth factors ALI acute lung injury ALP alkaline phosphatase ALT alanine aminotransferase AMI acute myocardial infarction ANG angiopoietin AQP5 aquaporin5 ArCr cartilaginous area ArOs osseous area ASC adipose stromal cell ASCST adipose MSCderived secretome ASMC amniotic stromal mesenchymal stem cells AST aspartate transaminase ATG5 autophagyrelated protein 5 ATMPs advanced therapy medicinal products AuBK aurora B kinase BBB Basso, Beattie, Bresnahan ratings Bcl2 Bcell lymphoma 2 BDNF brainderived neurotrophic factor Beclin 1 coiledcoil myosinlike BCL2interacting protein bFGF Basic fibroblast growth factor Bleo bleomycin BLM bleomycin BMP bone morphogenetic proteins BMSCs bone marrow mesenchymal stromal cells BrdU bromodeoxyuridine BST UCMSCs exposed to healthy brain extract CAT catalase CD control diet CD31 cluster of differentiation 31 CD44+/CD24 breast cancer cell phenotype associated with stem/progenitor cell properties CD68 cluster of differentiation 68 Cfl2 Cofilin2 CH human articular chondrocytes (CH) CHS cordycepininduced HaCaT secretome CLL2 chemokine (CCmotif) ligand 2 CM conditioned medium CNS Central Nervous System Col1A2 human collagen alpha2 type I Col3A1 collagen alpha1(III) chain Cox2 cyclooxygenase2 CXN43 connexin 43 DCF dichlorofluorescein DCX doublecortin dECM decellularised extracellular matrix DMEM Dulbecco's Modified Eagle Medium DNA deoxyribonucleic acid DPSCs dental pulp stem cells ECM extracellular matrix ECS extracellular space ECV304 immortal endothelial cell line ELISA enzymelinked immunosorbent assay EMT epithelialmesenchymal transition EPCs endothelial progenitor cells ER endoplasmic reticulum ESCMSC human embryonic stem cellinduced mesenchymal stem cell EV extracellular vesicles F4/80 marker for macrophages and dendritic cells FBS foetal bovine serum FGF fibroblast growth factor FR Dermal Fibroblasts G1 growth phase of cell cycle GDNF glial cell linederived neurotrophic factor GMP Good Manufacturing Practices GPX1 glutathione peroxidase 1 GSHPX glutathione peroxidase HA hyaluronic acid HaCaT immortalized, human keratinocyte line hAFs human amniotic fluidderived stem cells hBMMSC human bone marrowmesenchymal stem cell hBMSCs human bone marrow stromal cells HCEC human cardiac microvascular endothelial cells HDF Human Dermal Fibroblasts HDMECs human dermal microvascular endothelial cells hDPSC human dental pulpderived stem cell Hepatic I/R hepatic ischemia/reperfusion hESCMSC human embryonic mesenchymal stem cells hESCMSCIMRC human embryonic stem cellderived MSClike immune and matrix regulatory cells HFD highfat diet HFFs foreskin fibroblasts hFSSC human foetal skinderived stem cells hGFs human gingival fibroblasts Hif1 hypoxiainducible factor1 HiPSCs human induced pluripotent stem cells HIRI hepatic ischaemiareperfusion injury hMSC undifferentiated human mesenchymal stem cells hMSCEC human endothelial celldifferentiated mesenchymal stem cells HNF4 hepatocyte nuclear factor 4 HO1 heme oxygenase1 HSCs hepatic stellate cells HSP highscale production HUCMC human umbilical cord matrix cells hUCMSCs umbilical cord mesenchymal stem cells HUVEC human umbilical vein endothelial cells IBST UCMSCs exposed to injured brain extract IL interleukin IMRCs immune and matrix regulatory cells IPA Ingenuity Pathway Analysis IPF idiopathic pulmonary fibrosis IRI ischaemiareperfusion injury IV rTPA recombinanttissue plasminogen activator IV Intravenous Ki67 Antigen Kiel 67 LC3I cytosolic form of LC3 LC3ll LC3phosphatidylethanolamine conjugate LSC lung spheroid cell LSP lowscale production LV left ventricle LVEF left ventricular ejection fraction LX2 human hepatic stellate cell line M Phase mitotic phase of cell cycle MCP1 monocyte chemoattractant protein1 MDA malondialdehyde MDR1+ human Pglycoprotein encoded by the multidrug resistance 1 (MDR1) gene MI myocardial infarction MKI67 antigen Kiel 67 MMP matrix metalloproteinase MMSC placental multipotent mesenchymal stromal cell mNVCM neonatal mouse ventricular cardiomyocytes mRNA messenger RNA MSCCM secretome from human bone marrowderived mesenchymal stem cells MSCs mesenchymal stem cells NAC Nacetyl cysteine NaCl sodium chloride NGF nerve growth factor NOX4 nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 NRF2 nuclear factor erythroid 2related factor 2 NT3 neurotrophin3 OA osteoarthritis OC osteocalcin OPN osteopontin P53 tumor protein P53 p62 sequestosome1 (SQSTM1) PBMC peripheral blood mononuclear cell PBS phosphate buffered saline PCNA proliferating cell nuclear antigen PD pharmacodynamic PDGF plateletderived growth factor PDL1+ presence of programmed death1 ligand 1 (PDL1) protein in a tumor PIGF placental growth factor PK pharmacokinetic pNFb phosphorylated form of the nuclear factorB (NFB) transcription factor PPD phenotypic drug discovery ProSPC+positive AT2 cells proliferation of surfactant protein Cpositive AT2 cells pSTAT3 phosphorylated signal transducer and activator of transcription 3 PTX3 Pentraxin 3 rMSCs rat MSCs RNA ribonucleic acid ROS reactive oxygen species SCI spinal cord injury SD Sprague Dawley SDMSCs skinderived MSCs SERCA2 sarco/endoplasmic reticulum calcium ATPase 2 SGZ subgranular zone SMAD3 mothers against decapentaplegic homolog 3 SOCS3 suppressor of cytokine signaling 3 SOD superoxide dismutase SOD1 Superoxide dismutase 1 SPC surfactant protein C Sr90 Strontium90 ST USMSCs secretome without brain extract TAA thioacetamide TBI traumatic brain injury Tbil total bilirubin TGF transforming growth factor TIMPs tissue inhibitors of metalloproteinases TLRs tolllike receptors TNBC triple negative breast cancer TNF tumour necrosis factor TSP1 thrombospondin1 UCMSCs umbilical cord mesenchymal stem cells uPAR urokinasetype plasminogen activator receptor UPS unconventional protein secretion VEGF vascular endothelial cell growth factor VEGFA vascular endothelial cell growth factor A VEGFC vascular endothelial cell growth factor C vWF+ von Willebrand factor WHI wound healing index XFS xenofree medium Ym1 rodentspecific chitinaselike protein (CLP) lacking catalytic activity 1

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