3D-MSCs A151 ODN-loaded exosomes are immunomodulatory and reveal a proteomic cargo that sustains wound resolution

Camões, S.P.; Bulut, Özlem; Yazar, Volkan; Gaspar, Maria Manuela; Simões, Sandra; Ferreira, Rita; Vitorino, Rui; Santos, Jorge M.; Gürsel, İhsan; Miranda, Joana P.

doi:10.1016/j.jare.2022.01.013

Cited by 21 publications

(8 citation statements)

References 74 publications

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“…This process can solve the difficulty of encapsulating mRNA in exosomes and ameliorate the toxicity of liposomes, resulting in a greatly improved effect on colorectal cancer 74 . In addition to these genetic materials, researchers have successfully loaded various genetic materials into exosomes, including oligodeoxynucleotides 75 , 76 , long noncoding RNAs 77 , 78 , circular RNAs 79 , and adenoviruses 80 . In particular, clustered regularly interspaced short palindromic repeats (CRISPR), which of particular interest in genetic therapy, is also being studied intensively for loading into exosomes for targeted delivery 81 , 82 .…”

Section: Exosomes For Therapeutic Agent Deliverymentioning

confidence: 99%

Recent advances in extracellular vesicles for therapeutic cargo delivery

Kim,

Park,

Zhu

et al. 2024

Exp Mol Med

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Exosomes, which are nanosized vesicles secreted by cells, are attracting increasing interest in the field of biomedical research due to their unique properties, including biocompatibility, cargo loading capacity, and deep tissue penetration. They serve as natural signaling agents in intercellular communication, and their inherent ability to carry proteins, lipids, and nucleic acids endows them with remarkable therapeutic potential. Thus, exosomes can be exploited for diverse therapeutic applications, including chemotherapy, gene therapy, and photothermal therapy. Moreover, their capacity for homotypic targeting and self-recognition provides opportunities for personalized medicine. Despite their advantages as novel therapeutic agents, there are several challenges in optimizing cargo loading efficiency and structural stability and in defining exosome origins. Future research should include the development of large-scale, quality-controllable production methods, the refinement of drug loading strategies, and extensive in vivo studies and clinical trials. Despite the unresolved difficulties, the use of exosomes as efficient, stable, and safe therapeutic delivery systems is an interesting area in biomedical research. Therefore, this review describes exosomes and summarizes cutting-edge studies published in high-impact journals that have introduced novel or enhanced therapeutic effects using exosomes as a drug delivery system in the past 2 years. We provide an informative overview of the current state of exosome research, highlighting the unique properties and therapeutic applications of exosomes. We also emphasize challenges and future directions, underscoring the importance of addressing key issues in the field. With this review, we encourage researchers to further develop exosome-based drugs for clinical application, as such drugs may be among the most promising next-generation therapeutics.

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Section: Exosomes For Therapeutic Agent Deliverymentioning

confidence: 99%

Recent advances in extracellular vesicles for therapeutic cargo delivery

Kim,

Park,

Zhu

et al. 2024

Exp Mol Med

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“…Similar to BMMSC-EVs, EVs derived from 2D cultured UCMSCs have been found to exert protective effects in various ways, such as acute and chronic renal injury, heart injury, liver injury, brain injury, and immunomodulation, as well as alleviation of type 2 diabetes mellitus [ 23 , 173 – 179 ]. As with BMMSCs, in an in vivo wound healing model, EVs derived from 3D spheroid culture and 3D spinner flask culture of UCMSCs were able to promote epithelialization of wounds and accelerate post-injury skin healing, with a more dramatic effect than 2D-EVs [ 147 , 163 ]. Furthermore, exosomes derived from 3D cultured UCMSCs displayed stronger effects than 2D-Exos in repairing osteochondral damage, improving osteochondral activity, and promoting cartilage regeneration.…”

Section: Current Applications Of Evs Derived From 3d Cultured Scsmentioning

confidence: 99%

“…6 A) [ 147 ]. 3D-Exos loaded with A151 ODN (an exogenous immunosuppressive oligodeoxynucleotide) could induce systemic immunosuppression during the later stages of wound healing to aid wound healing [ 163 ]. For UCMSC-Exos, the best osteochondral repair results were obtained when 3D-Exos was combined with 3D-printed scaffolds (Fig.…”

Section: Current Applications Of Evs Derived From 3d Cultured Scsmentioning

confidence: 99%

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

Chen,

Wu,

Jin

et al. 2024

J Nanobiotechnol

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Stem cells (SCs) have been used therapeutically for decades, yet their applications are limited by factors such as the risk of immune rejection and potential tumorigenicity. Extracellular vesicles (EVs), a key paracrine component of stem cell potency, overcome the drawbacks of stem cell applications as a cell-free therapeutic agent and play an important role in treating various diseases. However, EVs derived from two-dimensional (2D) planar culture of SCs have low yield and face challenges in large-scale production, which hinders the clinical translation of EVs. Three-dimensional (3D) culture, given its ability to more realistically simulate the in vivo environment, can not only expand SCs in large quantities, but also improve the yield and activity of EVs, changing the content of EVs and improving their therapeutic effects. In this review, we briefly describe the advantages of EVs and EV-related clinical applications, provide an overview of 3D cell culture, and finally focus on specific applications and future perspectives of EVs derived from 3D culture of different SCs. Graphical Abstract

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Section: Bioengineering the Properties Of Mscexosomesmentioning

confidence: 99%

“…The protein-mediated mechanism of MSC-exosomes in wound healing has raised attention (Sung et al, 2019;Bari et al, 2020;Kudinov et al, 2021;Camões et al, 2022;Zhang et al, 2022). Comprehensive proteomic analysis showed that the proteins TGF-β, ITGA1-3/5, IL-6, CDC151, S100A10, and Wnt5α, as being enriched in MSC-exosomes in 3D culture, were confirmed to be associated with wound healing (Camões et al, 2022). In infected burn injury, PGE2, IL-6, IL-8, or IFN-γ, IL-10, growth factors, and chemokines secreted by placental MSC secretome were found to accelerate dermal fibroblast and keratinocyte migration and proliferation, stimulate angiogenesis, and reduce scarring (Kudinov et al, 2021).…”

Section: Bioengineering the Properties Of Mscexosomesmentioning

confidence: 99%

Bioengineered MSC-derived exosomes in skin wound repair and regeneration

Zhao

Wang

et al. 2023

Front. Cell Dev. Biol.

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Refractory skin defects such as pressure ulcers, diabetic ulcers, and vascular ulcers represent a challenge for clinicians and researchers in many aspects. The treatment strategies for wound healing have high cost and limited efficacy. To ease the financial and psychological burden on patients, a more effective therapeutic approach is needed to address the chronic wound. MSC-derived exosomes (MSC-exosomes), the main bioactive extracellular vesicles of the paracrine effect of MSCs, have been proposed as a new potential cell-free approach for wound healing and skin regeneration. The benefits of MSC-exosomes include their ability to promote angiogenesis and cell proliferation, increase collagen production, regulate inflammation, and finally improve tissue regenerative capacity. However, poor targeting and easy removability of MSC-exosomes from the wound are major obstacles to their use in clinical therapy. Thus, the concept of bioengineering technology has been introduced to modify exosomes, enabling higher concentrations and construction of particles of greater stability with specific therapeutic capability. The use of biomaterials to load MSC-exosomes may be a promising strategy to concentrate dose, create the desired therapeutic efficacy, and maintain a sustained release effect. The beneficial role of MSC-exosomes in wound healing is been widely accepted; however, the potential of bioengineering-modified MSC-exosomes remains unclear. In this review, we attempt to summarize the therapeutic applications of modified MSC-exosomes in wound healing and skin regeneration. The challenges and prospects of bioengineered MSC-exosomes are also discussed.

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3D-MSCs A151 ODN-loaded exosomes are immunomodulatory and reveal a proteomic cargo that sustains wound resolution

Cited by 21 publications

References 74 publications

Recent advances in extracellular vesicles for therapeutic cargo delivery

Recent advances in extracellular vesicles for therapeutic cargo delivery

Advances in the application of extracellular vesicles derived from three-dimensional culture of stem cells

Bioengineered MSC-derived exosomes in skin wound repair and regeneration

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