Therapeutic effects of combined cell transplantation and locomotor training in rats with brain injury

Abstract

Cell-based therapies are attracting attention as alternative therapeutic options for brain damage. In this study, we investigated the therapeutic effect of a combined therapy of cell transplantation and locomotor training by evaluating the neuronal connectivity. We transplanted neural cells derived from the frontal cortex of E14.5 GFP-expressing mice into the frontal lobe of 3-week-old rats with brain injury, followed by treadmill training (TMT) for 14 days. In the TMT(−) group, graft-derived neurites were observed only in the striatum and internal capsule. In contrast, in the TMT(+) group, they were observed in the striatum, internal capsule, and the cerebral peduncle and spinal cord. The length of the longest neurite was significantly longer in the TMT(+) group than in the TMT(−) group. In the TMT(+) group, Synaptophysin + vesicles on the neuronal fibers around the ipsilateral red nucleus were found, suggesting that neuronal fibers from the grafted cells formed synapses with the host neurons. A functional analysis of motor recovery using the foot fault test showed that, 1 week after the transplantation, the recovery was significantly better in the cell transplantation and TMT group than the cell transplantation only group. The percentage of cells expressing C-FOS was increased in the grafts in the TMT(+) group. In conclusion, TMT promoted neurite extensions from the grafted neural cells, and the combined therapy of cell transplantation and locomotor training might have the potential to promote the functional recovery of rats with brain injury compared to cell transplantation alone.

Telomerase Positive Totipotent Stem Cells and Pluripotent Stem Cells in the Adult Brain I. Cerebral Cortex

“…Recent evidence suggests that adult neural stem cells from subventricular region of lateral ventricles and the dentate gyrus of the hippocampus may play regenerative and reparative roles in response to CNS injury [38]. Cell-based transplantation therapies are viewed as an alternative option to regenerate and repair brain damage [39]. Such cells could be cultured and propagated neural stem cells isolated from the subventricular zone of lateral ventricles and the sub-granular zone of the dentate gyrus, embryonic human brain cells, embryonic rodent brain cells, immortalized progenitor cells, bone marrow-derived cells and post-mitotic neurons from human teratocarcinoma cells and have been studied in various model systems of brain damage [38][39][40][41][42][43].…”

“…Cell-based transplantation therapies are viewed as an alternative option to regenerate and repair brain damage [39]. Such cells could be cultured and propagated neural stem cells isolated from the subventricular zone of lateral ventricles and the sub-granular zone of the dentate gyrus, embryonic human brain cells, embryonic rodent brain cells, immortalized progenitor cells, bone marrow-derived cells and post-mitotic neurons from human teratocarcinoma cells and have been studied in various model systems of brain damage [38][39][40][41][42][43]. The model systems studied included integration into neuronal circuits, modification of local microenvironments, local trophic support and protection of regenerating neuronal cells [41][42][43].…”

Combination of Drugs and Cell Transplantation: More Beneficial Stem Cell-Based Regenerative Therapies Targeting Neurological Disorders

“…In order for more effective neuronal transplantation therapy, cell survival, neuronal maturation, neurite extension, and formation of synapses with host neurons are all necessary. To achieve these, therapeutic options in clinical and preclinical studies have included gene therapy, rehabilitation, and medication [29][30][31][32]. Medication is considered the most simple treatment option with regards to patient burden and avoids invasive surgical operations.…”

Computer Methods for Automatic Locomotion and Gesture Tracking in Mice and Small Animals for Neuroscience Applications: A Survey

“…Scientists can now breed genetically-altered mice called "transgenic mice" that carry genes that are similar to those that cause human diseases. Likewise, select genes can be turned off or made inactive, creating "knockout mice," which can be used to evaluate the effects of cancer-causing chemicals (carcinogens) and assess drug safety, according to the FBR [123,124,125,126,127,128,129]. Researchers working on anxiety in rats/small animals can also benefit from the methods described this survey because with a suitable gesture tracking/pose estimation method, they can quantify rats/animals behavior efficiently and understand how it alters with anxiety [130,131,132,133].…”

“…Scientists can now breed genetically-altered mice called "transgenic mice" that carry genes that are similar to those that cause human diseases. Likewise, select genes can be turned off or made inactive, creating "knockout mice," which can be used to evaluate the effects of cancer-causing chemicals (carcinogens) and assess drug safety, according to the FBR [123,124,125,126,127,128,129].…”