Diego Pastor

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

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.

Bone Marrow Transplantation in Hindlimb Muscles of Motoneuron Degenerative Mice Reduces Neuronal Death and Improves Motor Function

Bone marrow has proved to be an adequate source of stem cells for the treatment of numerous disorders, including neurodegenerative diseases. Bone marrow can be easily and relatively painlessly extracted from a patient or allogenic donor and then transplanted into the degenerative area. Here, the grafted cells will activate a number of mechanisms in order to protect, repair, and/or regenerate the damaged tissue. These properties make the bone marrow a feasible source for cell therapy. In this work, we transplanted bone marrow cells into a mouse model of motoneuron degeneration, with the particularity of placing the cells in the hindlimb muscles rather than in the spinal cord where neuronal degeneration occurs. To this end, we analyze the possibility for the transplanted cells to increase the survival rate of the spinal cord motoneurons by axonal-guided retrograde neurotrophism. As a result, the mice significantly improved their motor functions. This coincided with an increased number of motoneurons innervating the treated muscle compared with the neurons innervating the non-treated contralateral symmetric muscle. In addition, we detected an increase in glial-derived neurotrophic factor in the spinal cord, a neurotrophic factor known to be involved in the rescue of degenerating motoneurons, exerting a neuroprotective effect. Thus, we have proved that bone marrow injected into the muscles is capable of rescuing these motoneurons from death, which may be a possible therapeutic approach for spinal cord motoneuron degenerative diseases, such as amyotrophic lateral sclerosis.

Stem cell injection in the hindlimb skeletal muscle enhances neurorepair in mice with spinal cord injury

AIMS To develop a low-risk, little-invasive stem cell-based method to treat acute spinal cord injuries. methods: Adult mice were submitted to an incomplete spinal cord injury, and mesenchymal stem cells injected intramuscularly into both hindlimbs. Behavior tests and MRI of the spinal cord were periodically performed for up to 6 months, along with immunohistochemical analysis. Immunohistochemical and PCR analysis of the muscles were used to detect the grafted cells as well as the soluble factors released. RESULTS The stem cell-treated mice presented significant improvements in their motor skills 5 months after treatment. Spinal cord repair was detected by magnetic resonance and immunohistochemistry. In the hindlimb muscles, the stem cells activated muscle and motor neuron repair mechanisms, due to the secretion of several neurotrophic factors. CONCLUSION Bone marrow mesenchymal stem cell injection into hindlimb muscles stimulates spinal cord repair in acute spinal cord lesions.

Research Note: Efficiency in Attracting Tourists via the Web — An Application to the Mediterranean Countries

A key element of competitiveness in the tourism industry is the use of new information and communications technology (ICT). To analyse the efficiency in attracting tourists via the Web for a set of 16 Mediterranean countries, the authors use non-parametric bounded adjusted measure (BAM) models. Two models are proposed: the first analyses the influence of each countrys basic characteristics on the number of tourists who visit it, while the second relates these characteristics to the number of websites dedicated to tourism. The ordering provided by the two BAM models enables comparison of the efficiency in the real attraction of tourists with the effort of attracting them via the Web.

The Acute Effects of Exercise Intensity on Inhibitory Cognitive Control in Adolescents

Adolescence is an important stage for brain maturation. There are many studies of exercise-cognition relations, but there is still a lack of knowledge about the impact of combining different intensities of exercise on adolescents’ cognitive responses. The main objective of this study was to analyze the effect of three physical education sessions (based on Zumba dance) of different intensities (no exercise, predominantly light intensity, and predominantly vigorous intensity) on the inhibition response (measured with the Stroop test) in adolescents. Forty-four adolescent students (age 16.39 ± 0.68) completed a Stroop test before and after the three different physical education sessions. The results show than the predominantly vigorous session represented the strongest stimulus to increase cognitive inhibitory control. This means that the cognitive effect of exercise can be conditioned by exercise intensity and implies the need to control exercise intensity in physical educational programs for adolescents.

Bounded directional distance function models

AbstractBounded additive models in data envelopment analysis (DEA) under the assumption of constant returns to scale (CRS) were recently introduced in the literature (Cooper et al. in J Product Anal 35(2):85–94, 2011; Pastor et al. in J Product Anal 40:285–292, 2013; Pastor et al. in Omega 56:16–24, 2015). In this paper, we propose to extend the so far generated knowledge about bounded additive models to the family of directional distance function (DDF) models in DEA, giving rise to a completely new subfamily of bounded or partially-bounded CRS-DDF models. We finally check the new approach on a real agricultural panel data set estimating efficiency and productivity change over time, resorting to the Luenberger indicator in a context where at least one variable is naturally bounded.

The Reverse Directional Distance Function

The aim of any Data Envelopment Analysis (DEA) inefficiency model is to calculate the efficient projection of each unit belonging to a certain finite sample. The reverse directional distance function (RDDF) is a new tool developed in this chapter that allows us to express any known DEA inefficiency model as a directional distance function (DDF). Hence, given a certain DEA inefficiency model, its RDDF is a specific DDF that truly reproduces the functioning of the considered DEA model. Automatically, all the interesting properties that apply to any DDF are directly transferable to the considered DEA model through its RDDF. Hence, the RDDF enlarges the set of properties exhibited by any DEA model. For instance, given any DEA inefficiency model, its economic inefficiency—in any of its three possible versions—, can be easily defined and decomposed as the sum of technical inefficiency and allocative inefficiency thanks to the RDDF. We further propose to transform any non-strong DDF into a strong DDF, i.e., into a DDF that projects all the units onto the strongly efficient frontier. This constitutes another indication of the transference capacity of the RDDF, because its strong version constitutes in itself a strong version of the original DEA model considered. We further propose to search for alternative projections so as to minimize profit inefficiency, and add an appendix showing how to search for multiple optimal solutions in additive-type models.

Intramuscular transplantation of bone marrow cells prolongs the lifespan of SOD1G93A mice and modulates expression of prognosis biomarkers of the disease

BackgroundAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive muscle weakness, paralysis and death. There is no effective treatment for ALS and stem cell therapy has arisen as a potential therapeutic approach.MethodsSOD1 mutant mice were used to study the potential neurotrophic effect of bone marrow cells grafted into quadriceps femoris muscle.ResultsBone marrow intramuscular transplants resulted in increased longevity with improved motor function and decreased motoneuron degeneration in the spinal cord. Moreover, the increment of the glial-derived neurotrophic factor and neurotrophin 4 observed in the grafted muscles suggests that this partial neuroprotective effect is mediated by neurotrophic factor release at the neuromuscular junction level. Finally, certain neurodegeneration and muscle disease-specific markers, which are altered in the SOD1G93A mutant mouse and may serve as molecular biomarkers for the early detection of ALS in patients, have been studied with encouraging results.ConclusionsThis work demonstrates that stem cell transplantation in the muscle prolonged the lifespan, increased motoneuron survival and slowed disease progression, which was also assessed by genetic expression analysis.