Combining enriched environment and induced pluripotent stem cell therapy results in improved cognitive and motor function following traumatic brain injury

Abstract

Purpose: Despite advances towards potential clinically viable therapies there has been only limited success in improving functional recovery following traumatic brain injury (TBI). In rats, exposure to an enriched environment (EE) improves learning and fosters motor skill development. Induced pluripotent stem cells (iPSC) have been shown to survive transplantation and influence the recovery process. The current study evaluated EE and iPSC as a polytherapy for remediating cognitive deficits following medial frontal cortex (mFC) controlled cortical impact (CCI) injury. Methods: Sixty adult male rats received a midline mFC CCI or sham injury and were randomly placed in either EE or standard environment (SE). Seven days post-injury rats received bilateral transplantation of iPSCs or media. Behavioral measures were conducted throughout the remainder of the study. Following behavioral analysis, brains were extracted and prepared for histological analysis. Results: Open-field data revealed that combined therapy resulted in typical Sham/EE activity rearing patterns by the conclusion of the study. On the Vermicelli Handling task, rats with EE/iPSC polytherapy performed better than media-treated rats. Furthermore, rats treated with polytherapy performed equivalently to Sham/EE rats on the Morris water maze. Proficiency on the Rotarod was consistently better in EE when compared to SE counterparts. Confocal microscopy confirmed that iPSCs survived and migrated away from the transplantation site. Conclusions: Overall, EE or iPSC therapy improved cognition and motor performance, however, full cognitive restoration was seen only with the EE/iPSC treatment. These data suggest that EE/iPSC therapy should be explored as a potential, clinically relevant, treatment for TBI.

Neuroprotective effects of collagen matrix in rats after traumatic brain injury

“…Thus, collagen matrix has neuroprotective effect shown by behavioral and histological data after TBI. As future ideas for utilizing biomatrix for treatment of TBI develop further, combination of regenerative strategies such as behavioral training along with cell based therapies may have additional benefit (Dunkerson et al, 2014).…”

Potential of mesenchymal stem cells alone, or in combination, to treat traumatic brain injury

“…Later studies involved predifferentiating stem cells into more lineage‐restricted precursors in order to reduce the likelihood of tumorigenesis . In an effort to reduce reliance on embryonic or fetal tissue, there have been a number of studies more recently focused on induced pluripotent stem cells derived from adult somatic cells …”

The Potential of Stem Cells in Treatment of Traumatic Brain Injury

“…Thus far, the prospective of iPSCs for treating TBI has just begun to be explored. In TBI experimental studies, only two publications were found in PubMed reporting the use of iPSCs for post-TBI transplantation, these studies mainly reported the feasibility of using iPSCs providing very limited information about the fate of transplanted iPSCs in the injured brain [105, 106]. …”