bims-engexo 2024-12-22 papers

Biochim Biophys Acta Rev Cancer. 2024 Dec 16. pii: S0304-419X(24)00169-0. [Epub ahead of print]1880(1): 189238

Exosomes as a Therapeutic Strategy in Cancer: Potential Roles as Drug Carriers and Immune Modulators.

Azam Abedi, Mehrdad Moosazadeh Moghaddam, Reza Kachuei, Abbas Ali Imani Fooladi.

Exosome-based cancer immunotherapy is advancing quickly on the concept of artificially activating the immune system to combat cancer. They can mechanistically change the tumor microenvironment, increase immune responses, and function as efficient drug delivery vehicles because of their inherent bioactivity, low toxicity, and immunogenicity. Accurate identification of the mechanisms of action of exosomes in tumor environments, along with optimization of their isolation, purification, and characterization methods, is necessary to increase clinical applications. Exosomes can be modified through cargo loading and surface modification to enhance their therapeutic applications, either before or after the donor cells' isolation. These engineered exosomes can directly target tumor cells at the tumor site or indirectly activate innate and adaptive immune responses in the tumor microenvironment. This approach is particularly effective when combined with traditional cancer immunotherapy techniques such as vaccines, immune checkpoints, and CAR-T cells. It can improve anti-tumor responses, induce long-term immunity, and address the limitations of traditional therapies, such as poor penetration in solid tumors and immunosuppressive environments. This review aims to provide a comprehensive and detailed overview of the direct role of engineered exosomes as drug delivery systems and their immunomodulatory effects on tumors as an indirect approach to fighting cancer. Additionally, it will discuss novel immunotherapy options.

Keywords: CAR-T; Cancer immunotherapy; Direct/indirect effects; Exosome engineering; Immune checkpoint; Vaccination

DOI: https://doi.org/10.1016/j.bbcan.2024.189238

ACS Appl Mater Interfaces. 2024 Dec 19.

Prolonged Immunomodulator Delivery Boosts Monocyte Exosome Secretion and Elevates Cathelicidin/LL-37 Content.

Dezun Ma, Yajuan Su, Navatha Shree Sharma, Grant Hatcher, Gitali Ganguli-Indra, Arup K Indra, Adrian F Gombart, Jingwei Xie.

Human cathelicidin LL-37 offers significant benefits to the immune system and in treating various diseases, but its therapeutic potential is hindered by low activity and instability in physiological environments. Here, we introduce a strategy to boost LL-37 levels in exosomes derived from THP-1 monocytes by incubating cells with electrospun nanofibers containing immunomodulators (e.g., 1α, 25-dihydroxyvitamin D3 and VID400). Notably, the incubation with immunomodulator-loaded nanofibers not only increased LL-37 content in exosomes but also significantly enhanced the production of engineered exosomes. Moreover, these engineered exosomes demonstrated multiple biological activities, including promoting skin cell proliferation and migration, enhancing endothelial cell tube formation, and exhibiting antibacterial properties. Collectively, this study presents an approach to increasing both the yield of engineered exosomes and their LL-37 content, potentially offering a promising therapeutic option for wound healing, tissue regeneration, and infectious disease treatment.

Keywords: LL-37 expression; THP-1 cells; electrospun nanofibers; exosomes; immunomodulators

DOI: https://doi.org/10.1021/acsami.4c20695

Int J Mol Sci. 2024 Dec 05. pii: 13093. [Epub ahead of print]25(23):

Bioengineered Extracellular Vesicle Hydrogel Modulating Inflammatory Microenvironment for Wound Management.

Yunfei Mu, Liwen Ma, Jia Yao, Dan Luo, Xianguang Ding.

Chronic wounds, frequently arising from conditions like diabetes, trauma, or chronic inflammation, represent a significant medical challenge due to persistent inflammation, heightened infection risk, and limited treatment solutions. This study presents a novel bioengineered approach to promote tissue repair and improve the healing environment. We developed a bioactive hydrogel patch, encapsulated zeolitic imidazolate framework-8 (ZIF-8) into extracellular vesicles (EVs) derived from anti-inflammatory M2 macrophages, and synthesized ZIF@EV, then embedded it in the sodium alginate matrix. This hydrogel structure enables the controlled release of therapeutic agents directly into the wound site, where it stimulates endothelial cell proliferation and promotes new blood vessel formation. These processes are key components of effective tissue regeneration. Crucially, the EV-infused patch influences the immune response by polarizing macrophages towards an M2 phenotype, shifting the wound environment from inflammation toward regenerative healing. When applied in a murine model of chronic wounds, the EV hydrogel patch demonstrated notable improvements in healing speed, quality, and tissue integration compared to traditional approaches such as growth factor therapies and foam dressings. These promising findings suggest that this bioactive hydrogel patch could serve as a versatile, practical solution for chronic wound management, providing an adaptable platform that addresses both the biological and logistical needs of wound care in clinical settings.

Keywords: bioactive hydrogel; extracellular vesicles; tissue healing

DOI: https://doi.org/10.3390/ijms252313093

Int J Mol Sci. 2024 Nov 30. pii: 12911. [Epub ahead of print]25(23):

Mesenchymal Stromal Cells for Aging Cartilage Regeneration: A Review.

Kun-Chi Wu, Yu-Hsun Chang, Dah-Ching Ding, Shinn-Zong Lin.

Cartilage degeneration is a key feature of aging and osteoarthritis, characterized by the progressive deterioration of joint function, pain, and limited mobility. Current treatments focus on symptom relief, not cartilage regeneration. Mesenchymal stromal cells (MSCs) offer a promising therapeutic option due to their capability to differentiate into chondrocytes, modulate inflammation, and promote tissue regeneration. This review explores the potential of MSCs for cartilage regeneration, examining their biological properties, action mechanisms, and applications in preclinical and clinical settings. MSCs derived from bone marrow, adipose tissue, and other sources can self-renew and differentiate into multiple cell types. In aging cartilage, they aid in tissue regeneration by secreting growth factors and cytokines that enhance repair and modulate immune responses. Recent preclinical studies show that MSCs can restore cartilage integrity, reduce inflammation, and improve joint function, although clinical translation remains challenging due to limitations such as cell viability, scalability, and regulatory concerns. Advancements in MSC delivery, including scaffold-based approaches and engineered exosomes, may improve therapeutic effectiveness. Potential risks, such as tumorigenicity and immune rejection, are also discussed, emphasizing the need for optimized treatment protocols and large-scale clinical trials to develop effective, minimally invasive therapies for cartilage regeneration.

Keywords: aging; cartilage regeneration; mesenchymal stromal cells; osteoarthritis; regenerative medicine; tissue engineering

DOI: https://doi.org/10.3390/ijms252312911