Combining motor training with transplantation of rat bone marrow stromal cells does not improve repair or recovery in rats with thoracic contusion injuries

• Published in: Brain research Vol. 1119; no. 1; pp. 65 - 75
• Main Authors: Yoshihara, Hiroyuki, Shumsky, Jed S., Neuhuber, Birgit, Otsuka, Takanobu, Fischer, Itzhak, Murray, Marion
• Format: Journal Article
• Language: English
• Published: London Elsevier B.V 13.11.2006; Amsterdam Elsevier; New York, NY
• Subjects: Alkaline phosphatase; Animals; Animals, Genetically Modified; Biocompatible Materials - therapeutic use; Biological and medical sciences; Bone Marrow Transplantation - methods; Bone Marrow Transplantation - trends; Cell Differentiation - physiology; Development. Senescence. Regeneration. Transplantation; Exercise Therapy - methods; Female; Fundamental and applied biological sciences. Psychology; Graft Survival - physiology; Growth Cones - physiology; Growth Cones - ultrastructure; Humans; Motor training; Muscular Atrophy - physiopathology; Muscular Atrophy - prevention & control; Muscular Atrophy - therapy; Neuroglia - cytology; Neuroglia - metabolism; Neurons - cytology; Neurons - metabolism; Paralysis - physiopathology; Paralysis - rehabilitation; Paralysis - therapy; Physical Conditioning, Animal - physiology; Rat bone marrow stromal cell; Rats; Rats, Inbred F344; Rats, Sprague-Dawley; Recovery of Function - physiology; Spinal Cord Injuries - physiopathology; Spinal Cord Injuries - therapy; Spinal cord injury; Stromal Cells - transplantation; Thoracic Vertebrae; Transplantation; Treatment Outcome; Vertebrates: nervous system and sense organs; Rat bone marrow stromal cell; Alkaline phosphatase; Transplantation; Spinal cord injury; Motor training; Spinal cord; Rat; Enzyme; Rodentia; Central nervous system; Phosphoric monoester hydrolases; Esterases; Recovery; Vertebrata; Mammalia; Animal; Bone marrow; Hydrolases; Transplantation;Rat bone marrow stromal cell;Alkaline phosphatase;Motor training;Spinal cord injury; Stromal cell; Lesion; Repair
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2006.08.080

Previous studies have demonstrated that either transplantation of bone marrow stromal cells (MSC) or physical exercise regimens can elicit limited functional recovery following spinal cord injury, presumably through different mechanisms. The present study examined whether transplantation of MSC derived from transgenic Fischer alkaline phosphatase (AP) rats, in combination with exercise, would have synergistic effects leading to recovery of function that is greater than either alone. Adult female Sprague–Dawley rats received a moderate thoracic contusion injury and were divided into three groups: operated controls (Op-Control), MSC transplant recipients (MSC), and MSC transplant recipients plus exercise (MSC + Ex). Nine days after contusion, a Vitrogen matrix ± one million MSC was injected into the lesion site in all animals. Immunosuppression with high doses of Cyclosporine A, required for MSC survival, was provided for all animals. Passive hindlimb exercise on motorized bicycles was applied 1 h/day, 3 days/week to the MSC + Ex group. A battery of behavioral tests was performed weekly to assess motor and sensory functions in all 3 groups for 12 weeks. Morphological evaluation included MSC survival, evidence of axonal growth into grafts, phenotypic analysis of MSC, and lesion/transplant size. The weight of the medial gastrocnemius muscle, a hindlimb muscle activated during stance, was used to identify extent of atrophy. No differences in motor recovery were found among the three groups. MSC survived 3 months after transplantation, indicating that the immunosuppression treatment was successful. The extent of survival was variable, and there was no correlation between MSC survival and behavioral scores. The matrix persisted, filling the lesion cavity, and some axons grew into the lesion/matrix but to a similar extent in all groups. There was no difference in lesion/matrix size among groups, indicating no neuroprotective effect on the host provided by the treatments. Immunocytochemical analysis provided no evidence that MSC differentiated into neurons, astrocytes or oligodendrocytes. Muscle mass of the medial gastrocnemius was diminished in the Op-Control group indicating significant atrophy, but was partially preserved in both the MSC and MSC + Ex groups. Our results indicate that combining the beneficial effects of rat MSC and this exercise protocol was not sufficient to enhance behavioral recovery.