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Exosomes as Part of the Human Adipose-Derived Stem Cells Secretome- Opening New Perspectives for Cell-Free Regenerative Applications

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Part of the book series: Advances in Experimental Medicine and Biology ((CBTMED,volume 1312))

Abstract

Human adipose-derived stem cells (hASCs) represent a great resource for regenerative medicine based on their accessibility, self-renewal potential, low immunogenicity, high proliferative rate and potential to differentiate on multiple lineages. Their secretome is rich in chemokines, cytokines and protein growth factors that are actively involved in regeneration processes. In addition, part of this secretome are also the exosomes (hASC-exos), which display high content in proteins, messenger RNAs (mRNAs) and non-coding RNAs (ncRNAs). Due to their content, exosomes promote tissue regeneration by different mechanisms, either by activating or inhibiting several signaling pathways involved in wound healing, extracellular matrix remodeling, immunomodulation, angiogenesis, anti-apoptotic activity and cell migration, proliferation and differentiation. The use of hASC-exos may provide an improved alternative to standard therapies used in regenerative medicine, as a cell-free new approach with multiple possibilities to be modulated according to the patient needs. This review offers an updated overview on the functions and applications of hASC-exos in all areas of tissue regeneration, aiming to highlight to the reader the benefits of using hASCs in modern tissue engineering and regenerative medicine applications.

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Abbreviations

AFM:

atomic force microscopy

AK2:

adenylate kinase 2

AKI:

acute kidney injury

AKT:

Protein kinase B

Alix:

ALG2-interacting protein X

Arg-1:

arginase-1

AT:

adipose tissue

Bad:

Bcl associated agonist of cell death

Bax:

Bcl-2-associated X protein

Bcl-2:

B-cell lymphoma 2

BDNF:

brain-derived neurotrophic factor

bFGF:

basic fibroblast growth factor

Bim:

Bcl-2-like protein 11

BM-ASCs:

bone-marrow derived stem cells

BMEC:

brain microvascular endothelial cells

BMP:

bone morphogenetic proteins

CD:

cluster of differentiation

CM:

conditioned medium

Col2A1:

type II collagen alpha 1

COX:

cyclooxygenase

CSCs:

cancer stem cells

CSF-1R:

colony-stimulating factor 1 receptor

DDL4:

angiogenic inhibitor delta-like 4

Dvl:

Disheveled

ECM:

extracellular matrix

EGF:

epidermal growth factor

EPCs:

endothelial progenitor cells

ERK:

extracellular signal-regulated kinases

ESCRT:

endosomal sorting complex required for transport

EVs:

Extracellular vesicles

MVBs:

multivesicular bodies

FBS:

fetal bovine serum

FGF-1:

fibroblast growth factor 1

FIZZ:

found in inflammatory zone

G-CSF:

granulocyte colony stimulating factor

GDNF:

glial cell-derived neurotrophic factor

hASCs:

human adipose derived stem cells

HDFs:

Human dermal fibroblasts

HIPK2:

homeodomain interacting protein kinase 2

HR:

hypoxia/reoxygenation

HSP:

heat shock protein

IDO:

3-dioxygenase

IFN-γ:

interferon γ

IGF:

insulin-like growth factor

IL:

interleukin

IL-4Rα:

IL-4 receptor α

ILVs:

intraluminal vesicles

iNOS:

inducible nitric oxide synthase

IR:

Ischemia/reperfusion

IRAK1:

interleukin-1 receptor-associated kinase 1

IWR-1:

Wnt-β-catenin signaling inhibitor

JNK:

c-Jun N-terminal kinases

LASS2:

longevity assurance homologue 2

LECs:

lymphatic endothelial cells

lncRNA:

long non-coding RNA

MALAT1:

metastasis-associated lung adenocarcinoma transcript 1

MAPKs:

mitogen-activated protein kinases

MARK1:

microtubule affinity regulating kinase 1

Mcl-1:

myeloid leukemia cell differentiation protein 1

MCP:

monocyte chemoattractant protein

M-CSF:

macrophage colony stimulating factor

MHC:

major histocompatibility complex

miR:

microRNA

MMP:

matrix metalloproteinases

mRNAs:

messenger RNAs

ncRNAs:

non-coding RNAs

NF-kB:

nuclear factor-kB

NGF:

nerve growth factor

NK:

natural killer

NPCs:

neural precursor cells

Nrf2:

nuclear factor-E2-related factor 2

OA:

osteoarthritis

PCNA:

proliferating cell nuclear antigen

PDGF:

platelet-derived growth factor

PDGFA:

platelet-derived growth factor subunit A

PDGFR:

platelet-derived growth factor receptor

PDK1:

3-phosphoi-nositide-dependent protein kinase 1

PI3K:

Phosphoinositide 3-kinase

/PIP3:

phosphatidyl inositol 3, 4, 5-triphosphat

PKB:

Protein Kinase B

PLGA:

poly lactic-co-glycolic acid

PPARγ:

peroxisome proliferator-activated receptor γ

PREF-1:

preadipocyte factor 1

PTEN:

phosphatase and tensin homolog

S1P:

sphingosine 1 phosphate

S1PR1:

sphingosine 1 phosphate receptor 1

SDF-1:

stromal cell derived factor

SEM:

scanning electron microscopy

Sema:

semaphorin

SIRT1:

sirtuin 1

SK1:

sphingosine kinase 1

STAT3:

signal transducer and activator of transcription 3

TCF/LEF:

T-cell factor/lymphoid enhancer factor

TEM:

transmission electron microscopy

TGF-β:

transforming growth factor-β

TIMP:

tissue inhibitors of metalloproteinases

TLR4:

Toll-like receptor 4

TNF-α:

tumor necrosis factor-α

TRAF6:

NF receptor associated factor 6

TRPM7:

Transient receptor potential cation channel subfamily M member 7

TSG101:

Tumor susceptibility gene

VEGF:

vascular endothelial growth factor

VEGF-R:

VEGF receptors

Vsp4:

vacuolar sorting protein 4

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Correspondence to Sorina Dinescu .

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Dinescu, S. et al. (2020). Exosomes as Part of the Human Adipose-Derived Stem Cells Secretome- Opening New Perspectives for Cell-Free Regenerative Applications. In: Turksen, K. (eds) Cell Biology and Translational Medicine, Volume 11. Advances in Experimental Medicine and Biology(), vol 1312. Springer, Cham. https://doi.org/10.1007/5584_2020_588

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