14 Jan Enhanced Macrophages Developed to Decrease Inflammation in Traumatic Brain Injury
MedicalResearch.com Interview with:
Samir Mitragotri Ph.D.
Hiller Professor of Bioengineering
Hansjorg Wyss Professor of Biologically Inspired Engineering
Area Chair, Bioengineering
Core Faculty Member, Wyss Institute for Biologically Inspired Engineering
Harvard John A. Paulson School Of Engineering And Applied Sciences
MedicalResearch.com: What is the background for this study?
Response: Traumatic brain injury (TBI) has a heavy burden on the world, affecting ~70 million people globally each year. Despite its prevalence, there are no clinically approved treatments beyond symptom management. There is an urgent need to develop effective therapies to alleviate the damage caused by TBI.
MedicalResearch.com: What do macrophages typically do?
As part of the innate immune system, macrophages migrate to areas of injury to eat pathogens or debris and manage inflammation in response to injury or infection. However, in the majority of cases of TBI, there is no actual infection from a foreign pathogen, leading to excessive inflammation that spreads damage beyond the initial impact.
MedicalResearch.com: What are the main findings?
Response: Macrophages can be polarized into an anti-inflammatory neuroprotective state outside of the body. However, once macrophages reach pro-inflammatory injured brain regions, they can undergo a switch into a pro-inflammatory damaging state that can actually worsen injury. By equipping macrophages with discoid microparticles we like to call backpacks, anti-inflammatory drug release from the backpacks retains macrophage in their neuroprotective state. Treatment of pigs exposed to a cortical impact model of traumatic brain injury with backpack-macrophages resulted in a reduction in local and systemic inflammation, and ultimately reduced lesion volume by 56%.
MedicalResearch.com: What should readers take away from your report?
Response: Backpack-augmented macrophages constitute a viable and promising therapy for treating traumatic brain injury. This is the first study to use a macrophage cell therapy for any animal model of TBI. The positive impacts of macrophages as a cell therapy are only just beginning.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: In future studies, we would like to investigate how backpack-macrophages are exerting their neuroprotective effects. We believe that by reducing inflammation they may protect blood-brain barrier integrity, preventing hemorrhage from worsening injury. We would also like to continue evaluation of this therapeutic modality to proceed to clinical trials to evaluate their efficacy.
Disclosures: Please see the publication for disclosures.
Neha Kapate, Rick Liao, Ryan Luke Sodemann, Tawny Stinson, Supriya Prakash, Ninad Kumbhojkar, Vineeth Chandran Suja, Lily Li-Wen Wang, Mikayla Flanz, Rohan Rajeev, Dania Villafuerte, Suyog Shaha, Morgan Janes, Kyung Soo Park, Michael Dunne, Bryan Golemb, Alexander Hone, Kolade Adebowale, John Clegg, Andrea Slate, Declan McGuone, Beth Costine-Bartell, Samir Mitragotri, Backpack-mediated anti-inflammatory macrophage cell therapy for the treatment of traumatic brain injury, PNAS Nexus, Volume 3, Issue 1, January 2024, pgad434, https://doi.org/10.1093/pnasnexus/pgad434
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Last Updated on January 14, 2024 by Marie Benz MD FAAD