Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Gu, Zhewei; Yin, Zhimin; Song, Pengbo; Wu, Ying; He, Ying; Zhu, Maoshu; Wu, Zhengxin; Zhao, Sicheng; Huang, Hongri; Wang, Huihuang; Tong, Cailing; Qi, Zhongquan

doi:10.3389/fbioe.2022.949724

Cited by 12 publications

(11 citation statements)

References 59 publications

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“…Their efficiency in crossing the BBB is limited. Intravenous administration of exosomes results in their distribution primarily to the liver and kidneys, as was also observed in the present study. Peptide modification offers significant advantages.…”

Section: Discussionsupporting

confidence: 89%

RVG29 Peptide-Modified Exosomes Loaded with Mir-133b Mediate the RhoA-ROCK Pathway to Improve Motor and Neurological Symptoms in Parkinson’s Disease

Jiang,

Xiao,

et al. 2024

ACS Biomater. Sci. Eng.

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Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Drug delivery to the brain through the blood−brain barrier (BBB) is a significant challenge in PD treatment. Exosomes, which can efficiently traverse the BBB, which many drugs cannot penetrate, are ideal natural carriers for drug delivery. In this study, the BBB shuttle peptide was modified on the exosome surfaces. Three types of exosomes were constructed, each modified with a distinct peptide (RVG29, TAT, or Ang2) and loaded with miR-133b. The safety and brain-targeting capabilities of these peptide-modified exosomes were then evaluated. Finally, the mechanism by which RVG29-Exo-133b regulates the RhoA-ROCK signaling pathway was investigated. The findings indicate that the three peptide-modified exosomes were adequately tolerated, safe, and effectively assimilated in vivo and ex vivo, with RVG29 exhibiting superior targeting to the brain. Furthermore, RVG29-Exo-133b decreased the phosphorylation level of the Tau protein by targeting the RhoA-ROCK signaling pathway. It also enhanced the motor function in mice with PD, thereby reducing the degree of depression, improving dopaminergic neuron function, and attenuating 6-OHDA-induced nerve damage. In this study, we developed a stable drug delivery mechanism that targets the intracerebral region using exosomes. Furthermore, a novel strategy was developed to manage PD and can potentially serve as a preclinical basis for utilizing exosomes in the diagnosis and treatment of neurodegenerative conditions.

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Section: Discussionsupporting

confidence: 89%

RVG29 Peptide-Modified Exosomes Loaded with Mir-133b Mediate the RhoA-ROCK Pathway to Improve Motor and Neurological Symptoms in Parkinson’s Disease

Jiang,

Xiao,

et al. 2024

ACS Biomater. Sci. Eng.

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“…Tissue‐specific localization was identified in the liver, kidneys, brain, and lungs without significant adverse reactions. Specifically, evidence of hemolysis, DNA damage, and cytolytic effects were not observed; there were no abnormal histological findings, along with normal hemocyte, liver and kidney parameters, albeit with elevations in immunoglobulins and circulating CD8 + T cells 28 . Similar results were also reported in another in vivo study of exosomes isolated from mesenchymal stromal cells 29 .…”

Section: Resultssupporting

confidence: 82%

“…Specifically, evidence of hemolysis, DNA damage, and cytolytic effects were not observed; there were no abnormal histological findings, along with normal hemocyte, liver and kidney parameters, albeit with elevations in immunoglobulins and circulating CD8 + T cells. 28 Similar results were also reported in another in vivo study of exosomes isolated from mesenchymal stromal cells. 29 However, differences in experimental design hamper the clinical translation of these findings, and there remains an undetermined risk of tumor development and metastasis depending on the source and content of exosomes.…”

Section: Safetysupporting

confidence: 85%

“…A recent study performed safety evaluation of exosomes using in vitro and in vivo models 28 . Exosomes were isolated from human‐induced pluripotent stem cells.…”

Section: Resultsmentioning

confidence: 99%

“…26 A recent study performed safety evaluation of exosomes using in vitro and in vivo models. 28 Exosomes were isolated from humaninduced pluripotent stem cells. Tissue-specific localization was identified in the liver, kidneys, brain, and lungs without significant adverse reactions.…”

Section: Safetymentioning

confidence: 99%

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Systematic review of exosome treatment in hair restoration: Preliminary evidence, safety, and future directions

Gupta

Wang

Rapaport³

2023

J of Cosmetic Dermatology

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BackgroundExosomes are small extracellular vesicles with potential roles in modulating the hair growth cycle and are an emerging therapy for patients with alopecia. In recent years, researchers have made significant progress in deciphering the network of cellular interactions and signaling pathways mediated by the transfer of exosomes. This has opened the door to a wide range of potential therapeutic applications with an increasing focus on its application in precision medicine.AimTo evaluate current published evidence, both preclinical and clinical, on the use of exosomes for hair restoration.MethodsIn January 2023, a systematic search was conducted using PubMed, Embase, and the Cochrane Library. Records were identified, screened, and assessed for eligibility as per the PRISMA guideline.ResultsWe identified 16 studies (15 preclinical and 1 clinical) showing varying degrees of efficacy using exosomes derived from sources including adipose‐derived stem cells (ADSCs) and dermal papilla cells (DPCs). Applications of exosomes isolated from ADSCs (ADSC‐Exo) and DPCs have shown early promising results in preclinical studies corroborated by results obtained from different model systems. Topical ADSC‐Exo has been tried successfully in 39 androgenetic alopecia patients demonstrating significant increases in hair density and thickness. No significant adverse reactions associated with exosome treatment have been reported thus far.ConclusionsAlthough current clinical evidence supporting the use of exosome treatment is limited, there is a growing body of evidence suggesting its therapeutic potential. Further studies are warranted to define its mechanism of action, optimize its delivery and efficacy, and to address important safety concerns.

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HucMSC extracellular vesicles increasing SATB 1 to activate the Wnt/β‐catenin pathway in 6‐OHDA‐induced Parkinson's disease model

He,

Li,

et al. 2024

IUBMB Life

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Parkinson's disease (PD) is a degenerative disorder of the nervous system characterized by the loss of dopaminergic neurons and damage of neurons in the substantia nigra (SN) and striatum, resulting in impaired motor functions. This study aims to investigate how extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HucMSC) regulate Special AT‐rich sequence‐binding protein‐1 (SATB 1) and influence Wnt/β‐catenin pathway and autophagy in PD model. The PD model was induced by damaging SH‐SY5Y cells and mice using 6‐OHDA. According to the study, administering EVs every other day for 14 days improved the motor behavior of 6‐OHDA‐induced PD mice and reduced neuronal damage, including dopaminergic neurons. Treatment with EVs for 12 hours increased the viability of 6‐OHDA‐induced SH‐SY5Y cells. The upregulation of SATB 1 expression with EV treatment resulted in the activation of the Wnt/β‐catenin pathway in PD model and led to overexpression of β‐catenin. Meanwhile, the expression of LC3 II was decreased, indicating alterations in autophagy. In conclusion, EVs could mitigate neuronal damage in the 6‐OHDA‐induced PD model by upregulating SATB 1 and activating Wnt/β‐catenin pathway while also regulating autophagy. Further studies on the potential therapeutic applications of EVs for PD could offer new insights and strategies.

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Safety and biodistribution of exosomes derived from human induced pluripotent stem cells

Cited by 12 publications

References 59 publications

RVG29 Peptide-Modified Exosomes Loaded with Mir-133b Mediate the RhoA-ROCK Pathway to Improve Motor and Neurological Symptoms in Parkinson’s Disease

RVG29 Peptide-Modified Exosomes Loaded with Mir-133b Mediate the RhoA-ROCK Pathway to Improve Motor and Neurological Symptoms in Parkinson’s Disease

Systematic review of exosome treatment in hair restoration: Preliminary evidence, safety, and future directions

HucMSC extracellular vesicles increasing SATB 1 to activate the Wnt/β‐catenin pathway in 6‐OHDA‐induced Parkinson's disease model

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