Comparative Effects between Bone Marrow and Mesenchymal Stem Cell Transplantation in GDNF Expression and Motor Function Recovery in a Motorneuron Degenerative Mouse Model

摘要

Motorneuron degenerative diseases, such as amyotrophic lateral sclerosis (ALS), are characterized by the progressive and rapid loss of motor neurons in the brain and spinal cord, leading to paralysis and death. GDNF (glial cell line derived neurotrophic factor) has been previously shown to be capable of protecting motor-neurons in ALS animal models although its delivery to the spinal cord after systemic administration is blocked by the blood brain barrier. Thus, it is necessary to develop new neurotrophic approaches to protect these motor neurons from death. Bone marrow-derived stem cells have been shown to be capable of improving a large variety of neurodegenerative disorders through neurotrophic mediated mechanisms. Here we analyzed the effect of transplanting whole bone marrow or cultured mesenchymal stem cells into the spinal cord of a motor neuron degenerative mouse model. Motor functions were analyzed using various behavior tests for several weeks after transplantation. We observed that bone marrow, and to a lesser degree mesenchymal stem cell, treated mice improved significantly in the motor tests performed, coinciding with a higher GDNF immunoreactivity in the grafted spinal cord. In several cases, the treated spinal cords were extracted, the engrafted bone marrow cells isolated and cultured, and finally re-transplanted into the spleen of immunodeficient mice. Re-grafted cells were detected in the host spleen, bloodstream and bone marrow, demonstrating a phenotypic stability. Thus, bone marrow cells do not suffer significant phenotypic modifications and is an efficient procedure to ameliorate motor-neuron degeneration, making it a possible therapeutic approach.