Adipose tissue derived mesenchymal stem cell concentrated conditioned medium treatment is effective in long-term studies of mild traumatic brain injury

Abstract

Purpose : Previously we have demonstrated that intravitreal injection of adipose mesenchymal stem cell concentrated conditioned media (ASC-CCM) protected against the visual deficits of mild traumatic brain (mTBI) injury. In this study, we compared intravitreal injection of ASC-CCM to live ASCs to compare the long-term safety and effectiveness of both approaches.

Methods : C57Bl/6 mice approximately 12 weeks in age were subjected to a 50-psi air pulse on the left side of the head, resulting in an mTBI. Sham-blast mice served as the control. After the blast injury, 1 µl of human ASC-CCM (142 ng/mL total protein/eye) or 1 µl of human ASCs (1000 cells/eye) were delivered intravitreally. Rodents were followed up with visual function experiments and OCT at 1 and 5 months. Histological evaluation for GFAP was performed 1-month post-blast injury on some mice sacrificed at that time.

Results : Blast injury mice showed a decrease in visual acuity and an increase in the requirement for contrast compared to the sham blast mice. A significant improvement in visual acuity and contrast was observed at 1 and 5 months in blast mice receiving ASC-CCM compared to the blast mice. There was also a significant improvement in visual acuity and contrast with ASC at 1 month compared to the sham-blast mice (p<0.001), however the treatment effect was not sustained at 5-month in blast mice receiving ASC (p>0.5). Morphological analysis of retinas assessed by OCT 5-month post-blast showed normal appearance in all groups. Immunohistological analysis of retinas at one month post-TBI demonstrated increased expression of GFAP in the blast group (p<0.004) as compared to sham with a reduction observed with ASC-CCM (p<0.001) but not with ASCs (p>0.05). Histological evaluation of the 5-month time point is ongoing.

Conclusions : Our pilot and feasibility studies of live ASCs showed remarkable improvement in visual function at 1-month post-TBI, however the therapeutic effect did not appear at 5-month. On the other hand, ASC-CCM showed therapeutic benefit in long-term studies. Considering the lack of improvement in the Müller glial cell response in retina, our studies suggest that ASC-CCM has superior efficacy to live cells for the treatment of visual dysfunction in mTBI.

This is a 2020 ARVO Annual Meeting abstract.