Tissue Eng Regen Med.  2024 Apr;21(3):409-419. 10.1007/s13770-023-00613-1.

α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State

• Gopalakrishnan B
• Galili U
• Dunbar A
• Solorio L
• Shi R
• Li J

• KMID: 2554992
• DOI: http://doi.org/10.1007/s13770-023-00613-1

Abstract

BACKGROUND
Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, antiinflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state.
METHODS
Quiescent HMC3 cells were acutely exposed to α-gal nanoparticles in the presence of human serum and subsequently characterized for changes in cell shape, expression of anti or pro-inflammatory markers, and secretion of phenotype-specific cytokines.
RESULTS
HMC3 cells treated with serum activated α-gal nanoparticles exhibited rapid enlargement and shape change in addition to expressing CD68. Moreover, these activated cells showed increased expression of anti-inflammatory markers like Arginase-1 and CD206 without increasing production of pro-inflammatory cytokines TNF-α or IL-6.
CONCLUSION
This study is the first to show that resting human microglia exposed to a complex of α-gal nanoparticles and anti-Gal (from human serum) can be activated and polarized toward a putative M2 state. The data suggests that α-gal nanoparticles may have therapeutic relevance to the CNS microenvironment, in both recruiting and polarizing macrophages/microglia at the application site. The immunomodulatory activity of these α-gal nanoparticles post-SCI is further described in the companion work (Part II).

Keyword

Microglia; α-gal; Anti-inflammatory; Immunomodulation; Cytokines; Spinal cord injury