Bone marrow transplantation improves motor activity in a mouse model of ataxia.

Ataxias are locomotor disorders that can have an origin both neural and muscular, although both impairments are related. Unfortunately, ataxia has no cure, and the current therapies are aimed at motor re-education or muscular reinforcement. Nevertheless, cell therapy is becoming a promising approach to deal with incurable neural diseases, including neuromuscular ataxias. Here, we have used a model of ataxia, the Purkinje Cell Degeneration (PCD) mutant mouse, to study the effect of healthy (wild-type) bone marrow transplantation on the restoration of defective mobility. Bone marrow transplants (from both mutant and healthy donors) were performed in wild-type and PCD mice. Then, a wide battery of behavioural tests was employed to determine possible motor amelioration in mutants. Finally, cerebellum, spinal cord, and muscle were analysed to study the integration of the transplant-derived cells and the origin of the behavioural changes. Our results demonstrated that the transplant of wild-type bone marrow restores the mobility of PCD mice, increasing their capabilities of movement (52-100% of recovery), exploration (20-71% of recovery), speed (35% of recovery), and motor coordination (25% of recovery). Surprisingly, our results showed that bone marrow transplant notably improves the skeletal muscle structure, which is severely damaged in the mutants, rather than ameliorating the central nervous system. Although a multimodal effect of the transplant is not discarded, muscular improvements appear to be the basis of this motor recovery. Furthermore, the results from our study indicate that bone marrow stem cell therapy can be a safe and effective alternative for dealing with movement disorders such as ataxias.

Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy.

Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE), a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80%) and yield (>70%). Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies.

Lipoic acid and bone marrow derived cells therapy induce angiogenesis and cell proliferation after focal brain injury.

UNLABELLED: Abstract Introduction: Traumatic brain injury is a main cause of disability and death in developed countries, above all among children and adolescents. The intrinsic inability of the central nervous system to efficiently repair traumatic injuries renders transplantation of bone marrow-derived cells (BMDC) a promising approach towards repair of brain lesions. On the other hand, many studies have reported the beneficial effect of Lipoic acid (LA), a potent antioxidant promoting cell survival, angiogenesis and neuroregeneration. METHODS: In this study, the cortex of adult mice was cryo-injured in order to mimic local traumatic brain injury. Vehicle or freshly prepared BMDC were grafted in the cerebral penumbra area 24 hours after unilateral local injury alone or combined with intra-peritoneal LA administration as a new regenerative strategy. RESULTS: Differences were found in the process of cell proliferation, angiogenesis and glial scar formation after local injury depending of the applied treatment, either LA or BMDC alone or in combination. CONCLUSION: The data presented here suggest that transplantation of BMDC is a good alternative and valid strategy to treat a focal brain injury when LA could not be prescribed due to its non-desired secondary effects.