Abstract
Constructing biological substitutes that mimic the structure, architecture, and function of different tissues and organs is the ultimate goal of regenerative medicine. Adult mesenchymal stem/progenitor cells (MSCs) are considered the most widely researched cells in regenerative applications, yet several obstacles that challenge the safe and effective clinical translation of MSC-based therapies still exist. MSCs could partially exert their reparative and regenerative impact through a paracrine effect, mediated by the release of bioactive and trophic factors known as secretome, rather than the actual presence of the engrafted cells in the target site. In addition, MSCs have shown the ability to secrete these various bioactive molecules in their surrounding media (the conditioned media (CM)). MSC-secretome/CM is a set of proteins, lipids, nucleic acids, and trophic factors such as cytokines, chemokines, hormones, growth factors, and extracellular vesicles (EVs). Compared to nondental MSC secretome, dental MSC secretome/CM revealed a higher expression of proliferation-related, metabolic, transcriptional proteins and chemokines, as well as neurotrophins. Dental MSC secretome/CM exhibited experimentally tremendous biological effects, including immunomodulatory, anti-inflammatory, neuroprotective, osteogenic, angiogenic, and antiapoptotic effects, as well as the modulation of oxidative stresses. These aforementioned biological effects greatly explain the increasing interest in dental MSC secretome/CM as an acellular regenerative strategy for the treatment of various clinical diseases/injuries while alleviating the limitations and safety concerns associated with MSC-based therapies.
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Abbreviations
- 3D:
-
Three-dimensional
- ABMSCs:
-
Alveolar bone proper-derived stem/progenitor cells
- AD:
-
Alzheimer’s disease
- ALS:
-
Amyotrophic lateral sclerosis
- ASCs:
-
Adipose stem/progenitor cells
- bFGF:
-
Basic fibroblast growth factor
- BMMSCs:
-
Bone-marrow-derived mesenchymal stem/progenitor cells
- BMP:
-
Bone morphogenetic protein
- BNDF:
-
Brain-derived neurotrophic factor
- BSP:
-
Bone sialoprotein
- CCK-8:
-
Cell count kit-8
- c-JUN/JNK:
-
c-JUN/N-terminal kinase
- CM:
-
Conditioned medium
- CSF:
-
Colony-stimulating factor
- CXCL:
-
CXC motif ligand
- DFSCs:
-
Dental follicle stem/progenitor cells
- DMSCs:
-
Dental mesenchymal stem/progenitor cells
- DPSCs:
-
Dental pulp stem/progenitor cells
- DSPP:
-
Dentin sialophosphoprotein
- EAE:
-
Encephalomyelitis
- ECM:
-
Extracellular matrix
- EGF:
-
Epidermal growth factor
- EMVs:
-
Exosomes/Matrix vesicles
- EVs:
-
Extracellular vesicles
- EXs:
-
Exosomes
- FGF:
-
Fibroblast growth factor
- FGF-R:
-
Fibroblast growth factor-receptor
- FLT-3:
-
Fms-like tyrosine kinase receptor-3
- GCSF:
-
Granulocyte-colony-stimulating factor
- GDNF:
-
Glial-cell-line-derived neurotrophic factor
- GFAP:
-
Glial fibrillary acidic protein
- GM-CSF:
-
Granulocyte-macrophage colony stimulating factor
- GMSCs:
-
Gingival mesenchymal stem cells
- HEGF:
-
Heparin-binding epidermal growth factor
- HFSCs:
-
Hair follicle stem cells-CM
- HGF:
-
Hepatocyte growth factor
- HLA-DR:
-
Human leukocyte antigen-DR isotype
- HUVECs:
-
Human umbilical vein endothelial cell culture
- IFNγ:
-
Interferon gamma
- IGF:
-
Insulin-like growth factor
- IL:
-
Interleukins
- iNOS:
-
Inducible nitric-oxide synthase
- KGF:
-
Keratinocyte growth factor
- LF:
-
Liver failure
- MAPK:
-
Mitogen-activated protein kinase
- MCP-1:
-
Monocyte chemoattractant protein-1
- MS:
-
Multiple sclerosis
- MSCs:
-
Mesenchymal stem/progenitor cells
- MVs:
-
Microvesicles
- NF-Κb:
-
Nuclear factor-kappa B
- NGF:
-
Neural growth factor
- NT-3:
-
Neurotrophin-3
- OCN:
-
Osteocalcin
- Oct:
-
Octamer-binding transcription factor
- OSM:
-
Oncostatin M
- PCNA:
-
Proliferating cell nuclear antigen
- PDEGF:
-
Platelet-derived endothelial cell growth factor
- PDGF:
-
Platelet-derived growth factor
- PDL:
-
Periodontal ligament
- PDLSCs:
-
Periodontal ligament stem/progenitor cells
- PEI:
-
Polyethyleneimine
- PGE2:
-
Prostaglandin E2
- PLA:
-
Poly-(lactide)
- RUNX2:
-
Runt-related transcription factor 2
- SCAP:
-
Stem/progenitor cells from apical dental papilla
- SCF:
-
Stem cell factor
- SDF:
-
Stromal-cell-derived factor
- SHED:
-
Human shed deciduous teeth
- SOD:
-
Superoxide dismutase
- SOX-2:
-
Sex-determining region Y (SRY)-box 2
- sSiglec-9:
-
Soluble sialic-acid-binding Ig-like lectin-9
- TFIP11:
-
Tuftelin-interacting protein
- TGF-β:
-
Transforming growth factor β
- TIMP:
-
Tissue inhibitor of metalloproteinase
- TLR:
-
Toll-like receptor
- TNF-α:
-
Tumor necrosis factor-α
- TRAP:
-
Tartrate-resistant acid phosphatase
- TUFT1:
-
Tuftelin 1
- VEGF:
-
Vascular endothelial growth factor
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Radwan, I.A. et al. (2022). Current Trends and Future Outlooks of Dental Stem-Cell-Derived Secretome/Conditioned Medium in Regenerative Medicine. In: Haider, K.H. (eds) Handbook of Stem Cell Therapy. Springer, Singapore. https://doi.org/10.1007/978-981-16-6016-0_47-1
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