Abstract
Mesenchymal stem cells (MSCs) are, due to their capacity for immunosuppression, used in experimental and clinical trials as new therapeutic agents for the treatment of autoimmune and inflammatory diseases. However, there are serious safety concerns related to the unwanted differentiation and malignant transformation of engrafted MSCs. Since MSC-based immunosuppression was mainly attributed to the effects of MSC-derived factors, herewith we emphasized molecular and cellular mechanisms that were responsible for the beneficial effects of MSC-sourced secretome in the therapy of autoimmune and inflammatory diseases. MSC-derived extracellular vesicles (MSC-EVs) and MSC-conditioned medium (MSC-CM) are enriched with immunomodulatory factors that regulate phenotype and function of immune cells in injured tissues. Suppressed generation of inflammatory M1 macrophages, due to their conversion in M2 immunosuppressive phenotype, reduced capacity for antigen presentation of dendritic cells (DCs), and attenuated activation of T lymphocytes and natural killer T (NKT) cells were observed in MSC-EVs and MSC-CM-treated experimental animals. Therapeutic use of MSC-sourced secretome favored the development of tolerogenic DCs and induced expansion of immunosuppressive cells. Both local and systemic administration of MSC-derived factors resulted in an increased expansion of immunosuppressive M2 macrophages, FoxP3-expressing T, and NKT cells in inflamed tissues that led to the enhanced tissue repair and regeneration. Results obtained in a large number of animal studies and several clinical trials confirmed the beneficial effects of MSC-sourced bioactive products in the suppression of ongoing inflammation. In summing up, MSC-derived secretome could be considered as a new remedy for the treatment of autoimmune and inflammatory diseases.
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Abbreviations
- AF:
-
Amniotic fluid
- Ang-1:
-
Angiopoietin-1
- AT:
-
Adipose tissue
- CTLs:
-
Cytotoxic T-lymphocytes
- bFGF:
-
Basic fibroblast growth factor
- BNDF:
-
Brain derived neurotrophic factor
- DCs:
-
Dendritic cells
- DP:
-
Dental pulp
- ESCs:
-
Embryonic stem cells
- EVs:
-
Extracellular vesicles
- Exos:
-
Exosomes
- Exo-d-MAPPS:
-
Exosome-derived Multiple Allogeneic Protein Paracrine Signaling
- FasL:
-
First apoptosis signal ligand
- HGF:
-
Hepatic growth factor
- HO-1:
-
Hemeoxygenase-1 (HO-1)
- IDO:
-
Indolamine 2,3-dioxygenase
- IL:
-
Interleukin
- IL-R:
-
IL-1 receptor
- IL-Ra:
-
IL-1 receptor antagonist
- LECs:
-
Lung epithelial cells
- LPS:
-
Lipopolysaccharides
- MHC:
-
Major histocompatibility complex
- MicroRNAs:
-
miRNAs
- MIF:
-
Migration inhibitory factor
- M-CSF:
-
Monocyte colony-stimulating factor
- MSCs:
-
Mesenchymal stem cells
- MSC-CM:
-
MSC-derived conditioned medium
- MSC-Exos:
-
MSC-derived exosomes
- MSC-EVs:
-
MSC-derived extracellular vesicles
- NK:
-
Natural killer
- NKT:
-
Natural killer T-cells
- NO:
-
Nitric oxide
- OPN:
-
Osteopontin
- PAX5:
-
Paired box 5
- PGF:
-
Placental growth factor
- ST:
-
Synovial tissue
- TGF-β:
-
Transforming growth factor-β
- UC:
-
Umbilical cord
- PEDF:
-
Pigment epithelium-derived factor
- PGE2:
-
Prostaglandin E2
- PTECs:
-
Proximal tubular epithelial cells
- TSG-6:
-
TNF-α stimulated gene/protein 6
- VEFG:
-
Vascular endothelial growth factor
- TIMP1:
-
Tissue inhibitor of metalloproteinase-1
- TRAIL:
-
TNF-related apoptosis-inducing ligand
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Harrell, C.R., Volarevic, V. (2021). Mesenchymal Stem Cell-Derived Secretome: A New Remedy for the Treatment of Autoimmune and Inflammatory Diseases. In: Haider, K.H. (eds) Stem Cells. Springer, Cham. https://doi.org/10.1007/978-3-030-77052-5_4
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