The induction of sensorimotor recovery after cortical ablation by bone marrow-derived MSCs is in agreement to previous demonstrations of their efficiency to treat CNS injuries . However, we used the therapeutic window of 24 h after ablation, a protocol that is only possible using donor animals. Autologous transplantation of MSCs is unfeasible after too short time window, since its enrichment and its expansion are obtained after successive replating and cultivation for weeks . This delay hampers transplantation in acute or subacute phases of CNS lesions, when therapy should be more successful.
BMMCs have been suggested as an alternative for treatment of acute CNS injuries [1, 3, 17]. They can be obtained without cultivation and can be harvested in 1.5-6 h for autologous administration [18, 19]. In fact, BMMCs seem to be only effective when administrated in the acute/subacute phase of cerebral ischemia [4, 5]. We showed that BMMCs induced sensorimotor recovery with the same effectiveness of MSCs after cortical ablation. These results are in agreement to other comparative reports, which are scarce but have given support to the idea of BMMCs as an alternative to MSCs [5–7]. Moreover, we observed that the recovery promoted by BMMCs was sustained for at least three months, which is consistent with prior reports from our research group .
The present study deepens demonstration of therapeutic potential of bone marrow-derived cells, since we used a model of cortical lesion not yet used for cell-based therapies. Cortical ablation mimics a clinical condition of immediate removal of brain tissue, e.g., surgical removal of brain tumors. It is necessary to verify cell therapies efficacy in this debilitating condition, although its occurrence is significantly lower than stroke or traumatic brain injury (TBI). Moreover, cortical ablation model should be attractive for studies about mechanisms of action of therapies. Ablation differs from the natural inflammatory process of tissue removal that occurs after ischemia and TBI. Studies have suggested that inflammation induces lesion-induced structural plasticity, which is not observed after ablation [8, 10]. Increasing evidences have shown that inflammation triggers a return to a development-like condition, more permissive to axon regeneration and lesion-induced structural remodeling [8, 20]. Thus, our results were of interest, since we showed sensorimotor recovery induced by cell therapies in a model of lesion that does not cause significant structural plasticity [8–10].
Bone marrow-derived cells have been described to migrate to injured tissue and act as a local “factory” of molecules, promoting angiogenesis, neuroprotection, modulation of inflammatory response, reduction of glial scar and facilitation of axonal regeneration and plastic rewiring of neuronal connections [2, 21, 22]. In preliminary experiments, we have not found systemically administrated MSCs or BMMCs in the cortical lesion made by ablation (data not shown), which might suggest that bone marrow cells would act in ablation by systemic release of factors. However, further observations are needed to prove it.
Concluding, we demonstrated that MSCs and BMMCs are equally able to promote sensorimotor recovery. Thus, the study supports BMMCs as a cheaper and faster alternative for the treatment of CNS lesions, ideal for autologous transplantation in acute and subacute phases. Furthermore, these cells were able to promote recovery in a model of cortical lesion known for not being able to promote significant structural plasticity, a phenomenon believed to be essential for functional recovery. Thus, further studies are needed to explain the mechanisms underlying this recovery, verifying whether these cells are able to induce structural plasticity after ablation, and/or whether other mechanisms are lying beneath this therapeutic effect.