Table 3 Therapeutic applications of Extracellular vesicles

EVs

Adipose tissue

Pancreatic islets

C57BL/6J mice

Obese and Insulin-Resistance

GPCR, cAMP

PKA

Enhances insulin secretion in T2D patients

Mediators of obesity-associated Metabolic dysfunctions

^653,654

Exosomes and

EVs

MSCs

HFL1

T2DM using an HFD and STZ

Primary human skeletal muscle cells

T2DM

GLUT4,

p-GSK3β, PCNA,

Caspase3

Maintain glucose homeostasis

Relieves β-cell destruction

Reverses peripheral insulin resistance

^539,655

EVs

Macrophages

miR-32^−/− mice, T2DM mice

T2DM

miR-32, Mef2d,

cGMP-PKG

Autophagy inhibition of vascular smooth muscles

⁶⁵⁶

EVs carrying miRNAs

ADSCs

C57BL/KsJ db/m male mice

T2DM

Nephropathy

TLR4, Bcl-2, caspase-3, Bax,

IKKβ, IκBα,

VEGFA

Protects Diabetic Nephropathy

⁶⁵⁷

Metformin

Urine

db/db mice on a high salt diet,

mpkCCD cells

Diabetic Hypertension

cathepsin B, ENaC

Reducing high blood pressure

⁶⁵⁸

Dapagliflozin loaded exosomes

iPS-EC

Human iPSCs, iPS-ECs,

Diabetic Wound model

HIF-1α, VEGFA,

C-X-C motif chemokine receptor 4

Facilitate angiogenesis

Wound healing

⁶⁵⁹

EVs

Macrophage

M1 macrophage-induced HUVEC

Diabetic foot ulcer

miR-503, iNOS, Arg-1, IGF1R, ACO1

Regulates endothelial function affecting wound healing

⁶⁶⁰

EVs

Cardiomyocytes

ticagrelor-pretreated H9c2 cardiomyocytes

HUVEC

Cardiovascular

Bnip3, Beclin, Bax, ENT1, miR-499, miR-133

Reduced hyperglycemia-induced ROS production

Regulatory effect on diabetic cardiomyopathy

⁶⁶¹

Empagliflozin

MSCs

H9c2 cells, Myocardial infraction animal model

Cardiovascular disease

miR-214-3p, Bcl-2, BAX

Inhibited myocardial apoptosis

Reduced infarct size improved cardiac function

⁶⁶²

EVs

MSCs

Dendritic cells from CD14⁺ cells

T1DM mice

Type 1 Diabetes

IL-10, IL-6, IFN-γ, FOXP3⁺ regulatory T cells,

Th1, Th17

anti-inflammatory

cell therapy for autoimmune disease prevention

^663,664

EVs

2-E-EVs

CoV-2

Vero E6 cells

COVID-19

nAb-1, nAb-2

Cell-to-cell transmission of SARS-CoV-2

Facilitates neutralizing antibody entry into cells

⁶⁶⁵

EVs

MSCs

COVID-19 patients

THP1, Calu3, MVEC

Rat model of LPS-induced ALI

COVID-19

ACE2,

CD14,

TLR4

Reduce morbidity and mortality

Reduce lung inflammation

^666,667

iNSC-EVs

Neural stem cells

NSCs, iNSCs

Alzheimer’s disease

GFAP⁺, Tuj¹⁺ Iba¹⁺, Aβ_1-42

Therapeutic effects on cognitive function, neurodegeneration

⁶⁶⁸

EVs

Primary macrophages

Neurons astrocytes

Neuronal cells, Parkin Q311X(A) mice

Neurodegenerative disorder

Tetraspanins,

integrins

As nanocarriers for drug delivery to inflamed tissue

⁶⁶⁹

Vincristine (VCR)

Epidermoid carcinoma cells

KBv200 cells

Epidermoid carcinoma

ABCB1, Rab5, Rab8B

Increases sensitivity to chemotherapeutic drugs

⁶⁷⁰

Taxanes and Anthracyclines

Primary tumors

BC cells

4T1 cells,

C57BL/6, C57BL/6/Ccr2-KO mice,

Breast cancer

Anxa6,

CCR2

Pro-metastatic

Proinflammatory

⁶⁷¹

Paclitaxel (PTX)

PTX- BC cells

HUVECs

MCF-7

Breast cancer

circBACH1, miR-217, G3BP2 axis.

CircBACH1/ miR-217/G3BP2 axis a new regulatory for PTX-resistance and progression of breast cancer.

⁶⁷²

Cisplatin

Ovarian cancer cells

A2780, IGROV-1 cells

Ovarian cancer

CREB, ERK, JNK, p38α, p53

inhibits ovarian cancer

^673,674

Milk exosomes loaded with cisplatin

A2780, nu/nu mice

Ovarian cancer

ARF6, Rac1, CLTC, caveolin

Overcomes cisplatin-resistance in ovarian cancer

Temozolomide

Glioblastoma cells

U87-MG cells, GBM cells

Glioblastoma

Heat shock protein,

RAD51, MDM2

Leads to cell adhesion

⁶⁷⁵

EVs encapsulated miR-153-3p

LUAD cells

NCI-H1993, SW1271, BALB/c mice,

Lung adenocarcinoma

BANCR, miR-153-3p, PI3K/AKT

Increases cell invasion

⁶⁷⁶

EVs

PDAC cells

MIA PaCa-2, PANC-1,Rag2^−/−Ilrg2^−/−, mice

Pancreatic ductal adenocarcinoma

Rab27a, LRP-4 receptor, YAP

Intratumor communication

Targeted therapy for PDAC

⁶⁷⁷

EVs

Human Liver Stem Cells

MSCs

Renal cancer cells

SCID mice

Renal cell carcinoma

miR-Let7b, miR-200b, miR-200c and miR-223, EGFR, ZEB1, ZEB2, MMP1

antitumor effects

⁶⁷⁸