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From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine

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Abstract

In the fields of tissue engineering and regenerative medicine, extracellular vesicles (EVs) have become viable therapeutic tools. EVs produced from stem cells promote tissue healing by regulating the immune system, enhancing cell proliferation and aiding remodeling processes. Recently, EV has gained significant attention from researchers due to its ability to treat various diseases. Unlike stem cells, stem cell-derived EVs show lower immunogenicity, are less able to overcome biological barriers, and have a higher safety profile. This makes the use of EVs derived from cell-free stem cells a promising alternative to whole-cell therapy. This review focuses on the biogenesis, isolation, and characterization of EVs and highlights their therapeutic potential for bone fracture healing, wound healing, and neuronal tissue repair and treatment of kidney and intestinal diseases. Additionally, this review discusses the potential of EVs for the treatment of cancer, COVID-19, and HIV. In summary, the use of EVs derived from stem cells offers a new horizon for applications in tissue engineering and regenerative medicine.

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Abbreviations

EVs:

Extracellular vesicles

COVID-19:

Coronavirus disease 2019

HIV:

Human immunodeficiency virus

ISEV:

International Society for Extracellular Vesicles

MSCs:

Mesenchymal stem cells

MSC-EVs:

MSCs-derived EVs

ILVs:

Intraluminal vesicles

MVBs:

Multivesicular bodies

ESCRT:

Endosomal sorting complex required for transport

ALIX:

ALG-2-interacting protein X

TSG101:

Tumor susceptibility gene 101

SNAREs:

Soluble N-ethylmaleimide-sensitive factor attachment protein receptor

VAMP7:

Vesicle-associated membrane protein 7

PLD2:

Phospholipase D2

ARF6:

ADP ribosylation factor 6

PA:

Phosphatidic acid

DGKα :

Diacylglycerol kinase α

MT1-MMP:

Membrane type 1 matrix metalloprotease

PS:

Phosphatidylserine

PIP2:

Phosphatidylinositol 4,5-bisphosphate

ARRDC1:

Arrestin domain-containing protein-1

UC:

Ultra-centrifuge

SEC:

Size-exclusion chromatography

AF4:

Asymmetric flow field-flow fractionation

PBS:

Phosphate buffered saline

PES:

Polyethersulfone

TFF:

Tangential flow filtration

SEC:

Size exclusion chromatography

AFM:

Atomic force microscopy

TEM:

Transmission electron microscopy

FCM:

Fluorescence correlation microscopy

DLS:

Dynamic light scattering

RPS:

Resistive pulse sensing

RS:

Raman spectroscopy

FLOWER:

Frequency-locked optical whispering evanescent resonance

SP-IRI:

Single-particle interferometric reflectance imaging

NTA:

Nanoparticle tracking analysis

HSP:

Heat-shock proteins

EpCAM:

Epithelial cell adhesion molecule

EGFRs:

Epidermal growth factor receptors

LFA-1:

Lymphocyte function-associated antigen 1

ICAM-1:

Intercellular adhesion molecule-1

L1CAM:

L1 cell adhesion molecule

TGF- β:

Transforming growth factor β

MISEV2018:

Minimal information for studies of extracellular vesicles 2018

lncRNAs:

Long noncoding RNAs,

tRNA:

Transfer RNA

ECM:

Extracellular matrix

GPRC5B:

G-protein coupled receptor 5B

HGF:

Hepatic growth factor

SK2:

Sphingosine kinase 2

S1P:

Sphigosine-1-phosphate

SDF1:

Stromal-derived factor 1

MIF:

Macrophage inhibitory factor

ROS:

Reactive oxygen species

VEGF:

Vascular endothelial growth factor

EMMPRIN:

Extracellular matrix metalloproteinase inducer

MMP-9:

Matrix metalloproteinase-9

VEGFR2:

VEGF receptor 2

DMBT1:

Deleted in malignant brain tumors 1

NO:

Nitric oxide

Shh:

Sonic hedgehog

BMP-2:

Bone morphogenetic protein 2

ASCs:

Adipose derived stem cells

hBMSCs:

Human bone marrow mesenchymal stem cells

HIF-1α:

Hypoxia inducible factor

hUCMSCs:

Human umbilical cord mesenchymal stem cells

α-SMA:

α-Smooth muscle actin

HUVECs:

Human umbilical vein endothelial cells

NS:

Nervous system

BBB:

Blood–brain-barrier

SCI:

Spinal cord injury

OPCs:

Oligodendrocyte precursor cells

AKI:

Acute kidney injury

ARF:

Acute renal failure

CKD:

Chronic kidney disease

DN:

Diabetic nephropathy

IRI:

Ischemia–reperfusion injury

RVD:

Renovascular disease

ECD:

Expanded criteria donors

HOPE:

Hypothermic oxygenated perfusion

NR:

Normothermic reperfusion

IFN-γ:

Interferon gamma

NF-κB:

Nuclear factor kappa B

Il-6:

Interleukin 6

hPMSCs:

Human placental MSCs

IBD:

Inflammatory bowel disease

UC:

Ulcerative colitis

CD:

Crohn’s disease

AFMSC-EVs:

EVs and secretome derived from amniotic fluid mesenchymal stem cells

LPS:

Lipopolysaccharide

SEMFs:

SubEpithelial MyoFibroblasts

Tregs:

Regulatory T cells

DSS:

Dextran sulfate sodium

TNBS:

2,4,6-Trinitrobenzenesulfonic acid

NLRP3:

NOD-like receptor family, pyrin domain-containing 3

HFMSC-EVs:

Hair follicle-derived MSCs derived EVs

HCOEPIC:

Human colonic epithelial cell

NEC:

Necrotizing enterocolitis

ISCs:

Intestinal stem cells

AFSCs:

Amniotic fluid stem cells

HCC:

Hepatocellular carcinoma

NSCLC:

Non-small cell lung cancer

DTX:

Docetaxel

Dox:

Doxorubicin

PTX:

Paclitaxel

HIV:

Immunodeficiency virus

AIDS:

Acquired immunodeficiency syndrome

ARV:

Antiretroviral

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SBK conceptualized the review article; GA, JVJ, and SBK wrote the manuscript draft; SBK, AG, and SK revised it critically for intellectual content. All authors approved the final version of the manuscript.

Corresponding author

Correspondence to Shivaji B. Kashte.

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Arbade, G., Jose, J.V., Gulbake, A. et al. From stem cells to extracellular vesicles: a new horizon in tissue engineering and regenerative medicine. Cytotechnology (2024). https://doi.org/10.1007/s10616-024-00631-4

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