LESS INVASIVE INTRAPERITONEAL DELIVERY OF HUMAN IL-10 MRNA–LNP PROMOTES MORPHOLOGICAL AND FUNCTIONAL RECOVERY AFTER SPINAL CORD CONTUSION INJURY

Thousands of traumatic spinal cord contusion injuries occur annually worldwide, leading to extensive tissue damage and loss of motor, sensory, autonomic functions. Our laboratory previously successfully applied humanIL-10-mRNA therapy encapsulated in lipid nanoparticles (LNP), administered via intraspinal injection, for traumatic spinal cord contusion injury treatment, achieving significant improvement. We investigated whether intraperitoneally administered hIL-10-mRNA-LNP could be taken up and transported by resident macrophages to the injured spinal cord and induce morphological and functional improvement.
Traumatic spinal cord contusion injury was induced at the Th6 segment. Immediately following injury, hIL-10-mRNA-LNP was administered intraperitoneally. Control group animals received no treatment. During the survival period, at days 1 and 4 post-treatment, we mapped hIL-10-positive macrophages in the injured spinal cord using immunohistochemical methods. We performed functional tests (BBB test, video-based locomotor analysis), followed by detailed morphological analysis. Using retrograde labeling, we examined preservation and regeneration of affected pathways.
hIL-10-positive macrophages appeared in smaller numbers on day 1, and in greater numbers on day 4 within the injured spinal cord. Treated animals demonstrated significantly greater functional recovery compared to control group animals. Lesion area was significantly reduced in treated animals. Retrograde labeling studies, performed rostral to the lesion, demonstrated significant increases in FB-labeled (Fast Blue) neurons in the spinal cord, brainstem, and somatomotor cortex, supporting improved preservation and regeneration of propriospinal and supraspinal pathways. The improvement may be mediated by modulation of microglial/macrophage response and astroglial reaction.
Intraperitoneally administered mRNA-LNPs represent a less invasive yet effective therapeutic approach for traumatic spinal cord contusion injuries.