Evaluating Thera-101 as a Low-Volume Resuscitation Fluid in a Model of Polytrauma

Int J Mol Sci. 2022 Oct 21;23(20):12664. doi: 10.3390/ijms232012664.

Abstract

Traumatic brain injury (TBI) and hemorrhage remain challenging to treat in austere conditions. Developing a therapeutic to mitigate the associated pathophysiology is critical to meet this treatment gap, especially as these injuries and associated high mortality are possibly preventable. Here, Thera-101 (T-101) was evaluated as low-volume resuscitative fluid in a rat model of TBI and hemorrhage. The therapeutic, T-101, is uniquely situated as a TBI and hemorrhage intervention. It contains a cocktail of proteins and microvesicles from the secretome of adipose-derived mesenchymal stromal cells that can act on repair and regenerative mechanisms associated with poly-trauma. T-101 efficacy was determined at 4, 24, 48, and 72 h post-injury by evaluating blood chemistry, inflammatory chemo/cytokines, histology, and diffusion tensor imaging. Blood chemistry indicated that T-101 reduced the markers of liver damage to Sham levels while the levels remained elevated with the control (saline) resuscitative fluid. Histology supports the potential protective effects of T-101 on the kidneys. Diffusion tensor imaging showed that the injury caused the most damage to the corpus callosum and the fimbria. Immunohistochemistry suggests that T-101 may mitigate astrocyte activation at 72 h. Together, these data suggest that T-101 may serve as a potential field deployable low-volume resuscitation therapeutic.

Keywords: cell-based therapy; neuroprotection; organ damage; secretome; trauma.

MeSH terms

  • Animals
  • Brain Injuries, Traumatic* / drug therapy
  • Cytokines / therapeutic use
  • Diffusion Tensor Imaging
  • Disease Models, Animal
  • Hemorrhage / complications
  • Multiple Trauma* / therapy
  • Rats

Substances

  • Cytokines