Apoptotic Vesicles of MSCs: The Natural Therapeutic Agents and Bio‐Vehicles for Targeting Drug Delivery

Lin, Ruyi; Zhang, Tianyuan

doi:10.1002/smll.202301671

Cited by 11 publications

(1 citation statement)

References 82 publications

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“…Cells in the human body undergo apoptosis at all times, which is an essential metabolic process crucial for maintaining tissue and organ homeostasis [ 20 - 22 ]. This process generates a substantial number of apoptotic vesicles (apoVs) [ 23 - 25 ], which possess distinct molecular characteristics compared to exosomes and microvesicles [ 26 - 29 ]. ApoVs mediate intercellular communication by releasing and delivering various components, including DNAs, RNAs, lipids, and organelles inherited from parent cells.…”

Section: Introductionmentioning

confidence: 99%

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency

Zhang,

Mu,

Liu

et al. 2024

Preprint

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Apoptotic vesicles (apoVs) play a vital role in various pathological conditions; however, we have yet to fully understand their precise biological effects in rescuing impaired mesenchymal stem cells (MSCs) and regulating tissue homeostasis. Here, we proved that systemic infusion of bone marrow MSCs derived from wild-type (WT) mice effectively improved the osteopenia phenotype and hyperimmune state in ovariectomized (OVX) mice. Importantly, the WT MSCs rescued the impairment of OVX MSCs both in vivo and in vitro, whereas OVX MSCs did not show the same efficacy. Interestingly, treatment with apoVs derived from WT MSCs (WT apoVs) restored the impaired biological function of OVX MSCs and their ability to improve osteoporosis. This effect was not observed with OVX MSCs-derived apoVs (OVX apoVs) treatment. Mechanistically, the reduced miR-145a-5p expression hindered the osteogenic differentiation and immunomodulatory capacity of OVX MSCs by affecting the TGF-β/Smad 2/3-Wnt/β-catenin signaling axis, resulting in the development of osteoporosis. WT apoVs directly transferred miR-145a-5p to OVX MSCs, which were then reused to restore their impaired biological functions. Conversely, treatment with OVX apoVs did not produce significant effects due to their limited expression of miR-145a-5p. Overall, our findings unveil the remarkable potential of apoVs in rescuing the biological function and therapeutic capability of MSCs derived from individuals with diseases. This discovery offers a new avenue for exploring apoVs-based MSC engineering and expands the application scope of stem cell therapy, contributing to the maintenance of bone homeostasis through a previously unrecognized mechanism.

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Section: Introductionmentioning

confidence: 99%

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency

Zhang,

Mu,

Liu

et al. 2024

Preprint

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Immunogenicity of Extracellular Vesicles

Xia,

Zhang,

Liu

et al. 2024

Advanced Materials

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Extracellular vesicles (EVs) are promising next‐generation therapeutics and drug delivery systems due to demonstrated safety and efficacy in preclinical models and early‐stage clinical trials. There is an urgent need to address the immunogenicity of EVs (beyond the apparent lack of immunotoxicity) to advance clinical development. To date, few studies have assessed unintended immunological recognition of EVs. An in‐depth understanding of EV‐induced immunogenicity and clearance is necessary to develop effective therapeutic strategies, including approaches to mitigate immunological recognition when undesired. This article summarizes various factors involved in the potential immunogenicity of EVs and strategies to reduce immunological recognition for improved therapeutic benefit.

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Apoptotic extracellular vesicles: mechanisms, applications, and therapeutic potential

Han,

Li,

Wang

et al. 2024

Med-X

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Apoptotic extracellular vesicles (ApoEVs) are membrane-bound vesicles released during apoptosis, crucial for intercellular communication by delivering bioactive molecules to recipient cells. These vesicles are increasingly recognized for their potential in tumor therapy, immune modulation, and tissue regeneration. Recent studies reveal that ApoEVs play diverse roles in the medical fields. In tumor therapy, they enhance targeted drug delivery and antitumor immunity. Immune modulation is achieved by presenting antigens to immune cells, fostering specific responses. ApoEVs also aid in tissue regeneration, promoting wound healing and tissue repair. Advances in isolation and engineering techniques have improved the purity and functionality of ApoEVs, enabling their use as therapeutic delivery platforms. ApoEVs hold significant clinical potential by transferring genetic material, proteins, and other bioactive molecules. However, challenges such as standardizing production, ensuring safety, and addressing heterogeneity must be overcome. Future research should optimize isolation methods, elucidate ApoEV mechanisms, and develop strategies to enhance therapeutic efficacy. ApoEVs offer promising applications in cancer treatment, immune regulation, and tissue regeneration. This review summarizes the latest research and potential clinical applications of ApoEVs, highlighting their therapeutic promise and the challenges ahead. Graphical Abstract

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Apoptotic Vesicles of MSCs: The Natural Therapeutic Agents and Bio‐Vehicles for Targeting Drug Delivery

Cited by 11 publications

References 82 publications

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency

Apoptotic vesicles rescue impaired mesenchymal stem cells and their therapeutic capacity for osteoporosis by restoring miR-145a-5p deficiency

Immunogenicity of Extracellular Vesicles

Apoptotic extracellular vesicles: mechanisms, applications, and therapeutic potential

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