Secreted Factors and EV-miRNAs Orchestrate the Healing Capacity of Adipose Mesenchymal Stem Cells for the Treatment of Knee Osteoarthritis.
Adipose Tissue
/ metabolism
Chemokines
/ metabolism
Cytokines
/ metabolism
Homeostasis
Humans
Intercellular Signaling Peptides and Proteins
/ metabolism
Macrophages
/ metabolism
Mesenchymal Stem Cell Transplantation
Mesenchymal Stem Cells
/ metabolism
MicroRNAs
/ genetics
Osteoarthritis, Knee
/ therapy
Synovial Fluid
/ metabolism
Tissue Inhibitor of Metalloproteinase-1
/ metabolism
Tissue Inhibitor of Metalloproteinase-2
/ metabolism
Wound Healing
/ genetics
MSCs
cytokines
extracellular vesicles
fat tissue
joint
miRNAs
osteoarthritis
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
26 Feb 2020
26 Feb 2020
Historique:
received:
17
01
2020
revised:
21
02
2020
accepted:
24
02
2020
entrez:
1
3
2020
pubmed:
1
3
2020
medline:
15
12
2020
Statut:
epublish
Résumé
Mesenchymal stem cells (MSCs) derived from adipose tissue and used either as expanded cells or minimally manipulated cell preparations showed positive clinical outcomes in regenerative medicine approaches based on tissue restoration and inflammation control, like in osteoarthritis (OA). Recently, MSCs' healing capacity has been ascribed to the large array of soluble factors, including soluble cytokines/chemokines and miRNAs conveyed within extracellular vesicles (EVs). Therefore, in this study, 200 secreted cytokines, chemokines and growth factors via ELISA, together with EV-embedded miRNAs via high-throughput techniques, were scored in adipose-derived MSCs (ASCs) cultivated under inflammatory conditions, mimicking OA synovial fluid. Both factors (through most abundantly expressed TIMP1, TIMP2, PLG and CTSS) and miRNAs (miR-24-3p, miR-222-3p and miR-193b-3p) suggested a strong capacity for ASCs to reduce matrix degradation activities, as those activated in OA cartilage, and switch synovial macrophages, often characterized by an M1 inflammatory polarization, towards an M2 phenotype. Moreover, the crucial importance of selecting the target tissue is discussed, showing how a focused search may greatly improve potency prediction and explain clinical outcomes. In conclusion, herein presented data shed light about the way ASCs regulate cell homeostasis and regenerative pathways in an OA-resembling environment, therefore suggesting a rationale for the use of MSC-enriched clinical products, such as stromal vascular fraction and microfragmented adipose tissue, in joint pathologies.
Identifiants
pubmed: 32111031
pii: ijms21051582
doi: 10.3390/ijms21051582
pmc: PMC7084308
pii:
doi:
Substances chimiques
Chemokines
0
Cytokines
0
Intercellular Signaling Peptides and Proteins
0
MicroRNAs
0
TIMP1 protein, human
0
TIMP2 protein, human
0
Tissue Inhibitor of Metalloproteinase-1
0
Tissue Inhibitor of Metalloproteinase-2
127497-59-0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero della Salute
ID : Ricerca Corrente
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
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