13 Jul Exploring Platelet Generation: Insights from Lung Vasculature and Microfluidic Technology
Platelets play a crucial role in blood clotting and wound healing, but their complex generation process has remained a topic of intense research. In a recent breakthrough, scientists have shed light on the mechanisms of platelet generation using a combination of an ex vivo lung system and cutting-edge microfluidic technology. This innovative approach has not only enhanced our understanding of platelet formation but also holds the potential to revolutionize platelet production for medical applications.
“Using ex vivo lung and an in vitro microfluidic chamber we determine how oxygenation, ventilation, healthy pulmonary endothelium and the microvascular structure support thrombopoiesis. We also show a critical role for the actin regulator Tropomyosin 4 in the final steps of platelet formation in lung vasculature. This work reveals the mechanisms of thrombopoiesis in lung vasculature and informs approaches to large-scale generation of platelets.“, the authors explained.
The lung has emerged as a key site for platelet generation, with reports suggesting it produces a significant portion of total body platelets. By utilizing an ex vivo lung system integrated with a microfluidic device, researchers observed that anuclear fluorescent objects, resembling platelets, were present in the lung vasculature despite undetectable platelets in the perfusate. This finding enabled by microfluidic advancements suggests that the final steps of platelet generation, including enucleation, occur within the lung vasculature. It was also discovered that the protein TPM4 plays a critical role in the transformation of large anuclear fragments into platelets in the lung vasculature.
To further investigate platelet generation, researchers developed a microfluidic chip that mimics the capillary channels found in the body. This unique system allowed for the repeated passage of megakaryocytes (MKs) through microchannels, simulating the process within the lung vasculature. By leveraging microfluidic technology, the team achieved efficient platelet generation, with approximately 500 platelets produced per MK. This approach provides a promising avenue for large-scale platelet production outside the body.
The PDMS microfluidic chip used in the study was fabricated through microfluidic fabrication techniques, enabling precise control of channel dimensions and flow parameters. The design involved a branching structure that gradually reduced the channel diameter, resembling the vascular network. By multiplexing in parallel, the researchers scaled up the system to accommodate larger cell volumes, enhancing the efficiency of platelet generation. This demonstrates the power of microfabrication in creating sophisticated devices for biomedical applications.
The findings of this research have far-reaching implications for medicine. Understanding the intricate process of platelet generation opens doors for improved diagnostics and therapies related to platelet disorders and bleeding disorders. Furthermore, the microfluidic system developed in this study provides a promising platform for the large-scale production of platelets for transfusion purposes, potentially addressing the ongoing challenges of platelet shortages.
The combination of an ex vivo lung system and microfluidic technology has unveiled new insights into platelet generation. This research highlights the crucial role of the lung vasculature in platelet formation and showcases the potential of microfluidic devices for large-scale platelet production. As scientists continue to explore this fascinating field, the future of platelet research and medical applications looks promising.
“In summary, this work identifies a highly efficient mechanism for platelet generation outside of the body, by repeated passage of MKs through lung vasculature under air ventilation, involving enucleation and final TPM4-dependent steps to generate platelets. The findings will inform new approaches, such as the microfluidic system reported here, to large scale generation of human platelets. “, the authors explained.
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Figures are reproduced Zhao, X., Alibhai, D., Walsh, T.G. et al. Highly efficient platelet generation in lung vasculature reproduced by microfluidics. Nat Commun 14, 4026 (2023). https://doi.org/10.1038/s41467-023-39598-9
Read the original article: Highly efficient platelet generation in lung vasculature reproduced by microfluidics