From Apoptosis to Therapy: Applications of Apoptotic Bodies

In previous editions, we discussed the use of cellular products in regenerative medicine and immunotherapy, particularly microvesicles and exosomes. However, there is another type of vesicle produced during cell death that has recently gained attention: apoptotic bodies. In this article, we will answer basic questions such as: What are they? How are they formed? And what evidence exists regarding their utility and functionality?

What are they?

Apoptotic bodies, or ABs, are the largest extracellular vesicles found in the body. On average, they range in size from 1,000 to 5,000 nanometers. They are identified by the presence of phosphatidylserine on their membranes and their content of nuclear genetic material and cellular organelles.

They originate during the final stage of apoptosis, a programmed cell death process. During this process, genetic material is degraded and the cellular membrane is reshaped by kinases that elongate it, forming long protrusions called apoptopodia. These protrusions are then fragmented into 10 to 20 relatively uniform apoptotic bodies due to cytoskeletal contractions and increased hydrostatic pressure. They are, in fact, the only vesicles formed exclusively through this mechanism.

Clearance of apoptotic bodies

Throughout apoptosis, soluble mediators such as ATP, UTP, and CX3CL1 (fractalkine) are released, creating a chemotactic gradient. This gradient attracts macrophages and other cells that clean the microenvironment in a process known as efferocytosis. Apoptotic bodies, therefore, play a role in tissue homeostasis, pathogen dissemination, and immune regulation. Their therapeutic potential is becoming increasingly evident.

Potential applications

Research on apoptotic bodies has grown significantly in recent years. Although no clinical trials have been reported to date, their potential has been recognized in several areas:

– Diagnostics: They may carry tumor-related or pathogen-derived antigens that can be identified by the immune system, making them valuable biomarkers.

– Therapeutic evaluation: Apoptotic bodies are being studied as tools to assess drug-induced damage, transplant rejection, cancer treatment efficacy, and immune disorders.

Examples from recent studies

– Wound healing and skin grafts (2024): ABs derived from fibroblasts were administered subcutaneously during surgery. Inflammatory markers decreased, pro-inflammatory M1 macrophages were reduced, and anti-inflammatory M2 macrophages were promoted.

– Atherosclerosis: Necrotic plaques cause inflammation. Inducing apoptosis may help resolve these lesions. ABs could be administered or generated in vivo.

– Bone regeneration: Osteoclast-derived ABs have been shown to enhance viability and differentiation of pre-osteoblastic cells.

Limitations and challenges

Despite their potential, apoptotic bodies have notable limitations:

– High heterogeneity: Their contents vary depending on the cell type and apoptosis conditions, complicating standardization and limiting reproducibility.

– Low stability: They are rapidly cleared from the body, making sustained therapeutic use difficult.

– Cargo transport: Strategies like electroporation or stimulus-driven loading are under development, but rapid clearance continues to limit their clinical effectiveness.

Conclusions

We are only beginning to glimpse the therapeutic potential of apoptotic bodies. While their immunomodulatory, diagnostic, and regenerative capacities are promising, further research is required to ensure safe and effective clinical application.

At Baja Regenerative, we believe scientific knowledge and rigorous validation are essential before offering new therapies to patients. If you want to learn more about these strategies or explore their clinical applications, feel free to contact us for personalized guidance.

References:

• Hu Z., Qian S., Zhao Q., Lu B., Lu Q., Wang Y., Zhang L., Mao X., Wang D., Cui W. y Sun X. (2024). Engineering strategies for apoptotic bodies. Smart Med. 3 (3). E20240005
• Phan T., Ozkocak D. e Poon I. (2020). Unleashing the therapeutic potential of apoptotic bodies. Biochemical Society Transactions (48): 2079-2088.
• Yu G., Chen Y., Yang N., Zhang H., Zhang X., Geng Y., Zhao J., ChenZ., Dong C., Lin L., Qi J., Zhang X., Jiang X., Gao W., Cai Y., Wang X., Ding J., Xiao J. y Zhou K. (2024). Apoptotic Bodies Derived from Fibroblast-Like Cells in Subcutaneous Connective Tissue Inhibit Ferroptosis in Ischaemic Flaps via the miR-339-5p/KEAP1/Nrf2 Axis. Sci. 11. 2307238

Author: Biol. Fernando Vallejo Santín