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Table 1 Therapeutic potential of MSC exosomes in the context of regenerative medicine

From: Mesenchymal stem/stromal cell-derived exosomes in regenerative medicine and cancer; overview of development, challenges, and opportunities

Condition

MSC source

Isolation method

Mechanism

Main outcome

Ref

MI

Cardiac MSC

Precipitation at 4 °C with 5× polyethylene glycol 4000

Transferring miRs

Promoting cardiac angiogenesis and activating cardiomyocyte proliferation (animal study)

[88]

MI

BM-MSC

ExoQuick Exosome Precipitation Solution

Delivering miR-221 and miR-19a

Higher protective effects in cardiomyocytes promoted the growth of cardiomyocytes and prevented cell apoptosis (animal study)

[89, 90]

MI

BM-MSC

Ultracentrifugation (110,000×g)

Delivering miR-210 that decreases the expression of ephrin-A3

Promoted angiogenesis and cardiac function (animal study)

[91]

Myocardial IRI

HuES9.E1-derived MSC

Chromatography columns

Stimulating anti-apoptotic pathways and also inhibiting pro-apoptotic pathways

Enhanced bioenergetics and pro-survival signaling of cardiac cells (animal study)

[92]

MI

BM-MSC

ExoQuick-TC

n.a

Inducing neovascularization and suppressing inflammatory response (animal study)

[93]

MI

BM-MSC

Ultracentrifugation (200,000×g)

Delivering MiR-125b-5p

Inhibited apoptosis of cardiomyocyte through inhibition of pro-apoptotic genes p53 and BCL2-antagonist/killer 1 (BAK1) (animal study)

[94]

Autoimmune hepatitis

BM-MSC

Ultracentrifugation (100,000×g)

Delivering exosomal miR-223

Downregulating various inflammatory genes and proteins and inhibition of hepatocyte death (animal study)

[95]

Hepatic oxidant injury

UC-MSC

Ultracentrifugation (100,000×g)

Delivering glutathione peroxidase 1 (GPX1)

Suppressed oxidative stress and apoptosis on CCl4-and H2O2-induced hepatic damage (animal study)

[96]

LF

HuES9.E1-derived MSC

High-performance liquid chromatography (HPLC)

Increasing the expression of cyclin D1 and PCNA as proliferative proteins and enhancing expression of Bcl-xL as an anti-apoptotic factor

Promoting hepatocyte proliferation and inhibiting hepatocyte apoptosis (animal study)

[97]

Liver fibrosis

BM-MSC

Ultracentrifugation (100,000×g)

Lowering the plasma level of alanine aminotransferase and modulating expression level of inflammatory cytokines and regulatory T cells

Inducing hepatoprotective and anti-inflammatory effects (animal study)

[98]

LF

ESC-MSC

Ultracentrifugation (100,000×g)

n.a

Enhanced anti-apoptosis, anti-fibrosis, and regenerative capacity (animal study)

[99]

LF

BM-MSC

Ultracentrifugation (100,000×g)

Delivering Y-RNA-1

Modulated inflammatory response and by inducing multiple anti-apoptotic genes (animal study)

[100]

AD

WJ-MSC

Ultracentrifugation (100,000×g)

Delivering catalase

Decreasing neuronal oxidative stress and synapse damage (animal study)

[101]

Brain stroke

BM-MSC

Ultracentrifugation (100,000×g)

Transferring miR-133b to neighboring astrocytes and neuron cells

Increased functional regeneration (animal study)

[102]

SCI

BM-MSC

n.a

Enhanced neuro-vascularization and weaken neuronal apoptosis, as well as prevent inflammation and inhibit the neurotoxic of A1 astrocytes

Boosted SCI functional recovery (animal study)

[103]

SNI

UC-MSCs

Ultracentrifugation

Promoted the generation of axons and Schwann cells, minimized muscular atrophy, and induced anti-inflammatory reactions

Improved functional recovery and peripheral nerve regeneration (animal study)

[104]

SNI

Gingiva MSC

ExoQuick Exosome Precipitation Solution (SBI Systems Biosciences)

Expression of phenotype-related genes, c-Jun, Notch1, GFAP, Sox2 and the stimulation of JNK pathways

Regeneration of peripheral nerve (animal study)

[105]

MS

AT-MSC

Ultracentrifugation (100,000×g)

Reducing the number of Iba-1-positive microglial cells and also the plasma levels of inflammatory cytokines

Modulated microglial activity and improved immunomodulatory activities (animal study)

[88]

AKI

UC-MSCs

Ultracentrifugation (100,000×g)

Transferring hepatocyte growth factor (HGF) mRNA

Improved dedifferentiation and proliferation of damaged cells (animal study)

[89]

Kidney IRI

n.a

n.a

Delivering miR-22 for mTOR/HIF feedback interaction pathway and suppressing (PDCD4)/NFKB pathways

Stimulating kidney protection by inducing anti-inflammatory responses and reducing epithelial cell damage (animal study)

[106]

Kidney IRI

WJ-MSC

Ultracentrifugation (100,000×g)

Reduced kidney cell apoptosis and boosted anti-inflammatory responses

Downregulated CX3CL1 expression and improved kidney function (animal study)

[107]

AKI

UC-MSCs

Ultracentrifugation (100,000×g)

Activation of the ERK 1/2 pathway and inhibition of the p38MAPK pathway

Suppressing oxidative stress, inducing cell growth, and reducing kidney cell apoptosis (animal study)

[108]

CKD

Urinary MSC

Ultracentrifugation (100,000×g)

Delivering effective growth factors

Inhibited cell apoptosis and increased vascular regeneration (animal study)

[109]

Kidney artery stenosis

AT-MSC

n.a

Delivering anti-inflammatory cytokine interleukin (IL) 10

Attenuated kidney inflammation and fibrosis, increased kidney blood supply, and suppressed glomerular filtration (animal study)

[110]

Kidney fibrosis

BM-MSC

ExoQuick Exosome Precipitation Solution

Delivering exogenous microRNA let7c

Suppression of kidney inflammation (animal study)

[111]

ALI

UCB-MSC

Ultracentrifugation (100,000×g)

Delivering VEGF

Restored impaired alveoli function, angiogenic effects, and anti-inflammatory responses and minimized cell apoptosis (animal study)

[112]

ALI

AT-MSC

Ultracentrifugation

Delivering miRNA

Attenuating ALI damage and macrophages polarization (animal study)

[113]

Lung IRI

BM-MSCs

n.a

Transferring miR-21-5p

Inhibited lung edema and improved the function of wound healing (animal study)

[114]

ALI

BM-MSC

Ultracentrifugation

Transferring KGF

Promoted immunomodulatory effects and increased intracellular ATP levels of alveolar epithelial type 2 cell (animal study)

[115]

ALI

BM-MSC

Ultracentrifugation (100,000×g)

Transferring mitochondrial

Inhibited the production of inflammatory cytokines and enhanced phenotype 2 of alveolar macrophages (animal study)

[116]

PAH

BM-MSC

Ultracentrifugation (100,000×g)

Alleviated pressure, inhibited right ventricle hypertrophy, and restored pulmonary function

Improved pulmonary artery hypertension (animal study)

[117]

  1. Note: ALI acute lung injury, MI myocardial infarction, LF liver failure, IRI ischemia-reperfusion injury, PAH pulmonary arterial hypertension, AKI acute kidney injury, CKD chronic kidney disease, SCI spinal cord injury, SNI spared nerve injury, AD Alzheimer’s diseases, MS multiple sclerosis, BM bone marrow, AT adipose tissue, UC umbilical cord, UCB umbilical cord blood, WJ Wharton’s jelly, miRs microRNAs, n.a not available