Coculture of Axotomized Rat Retinal Ganglion Neurons with Olfactory Ensheathing Glia, as an In Vitro Model of Adult Axonal Regeneration.

pre-print283 K

Cross-Cultural Adaptation and Validation of the Perceptions of Empowerment in Midwifery Scale in the Spanish Context (PEMS-e)

Midwifery empowerment is an important topic. The most widely used instrument to measure the perceived empowerment of midwives is the Perceptions of Empowerment in Midwifery Scale (PEMS), which has not been validated in Spain. The aim of this study was to translate and adapt the PEMS to the Spanish context. This research was carried out in two phases; Phase 1: Methodological study; translation, backtranslation and cross-cultural adaptation of the PEMS and pilot study on the target population (10 midwives) for evaluation of face validity. Phase 2: Cross-sectional observational study to obtain a sample for construct validation by Exploratory Factor Analysis and measurement of PEMS-e reliability. Additionally, an inferential analysis was carried out to study the possible association between several collected variables and PEMS-e subscale-scores. A total of 410 midwives from 18 Spanish regions participated in the study through an online questionnaire. An initial Spanish version of the PEMS scale was produced, demonstrating adequate face validity. A final model was produced for the PEMS-e, which included 17 items classified into two subscales (“Organizational support” and “Own skills and teamwork”) with fit indexes RMSEA = 0.062 (95%CI: 0.048–0.065) and AGFI = 0.985 (95%CI: 0.983–0.989) and Cronbach’s alpha 0.922 for the total scale. Results showed that one in four midwives had considered abandoning the profession in the last 6 months (p ≤ 0.001). This research suggests that Spanish midwives perceive their empowerment level as low. The PEMS-e is a valid tool with solid psychometric properties that can be used in future research to identify factors that contribute to increased empowerment among Spanish midwives and inform strategies to improve job satisfaction and retention in the profession

Cell therapy for spinal cord injury with Olfactory Ensheathing Glia Cells (OECs)

This is the peer reviewed version of the following article: Gómez RM, Sánchez MY, Portela-Lomba M, et al. Cell therapy for spinal cord injury with olfactoryensheathing glia cells (OECs). Glia. 2018;00:1–35 which has been published in final form at GLIA 13 January (2018) http://doi.org/10.1002/glia.23282. © 2018 Wiley Periodicals This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.The prospects of achieving regeneration in the central nervous system (CNS) have changed, asmost recent findings indicate that several species, including humans, can produce neurons in adult-hood. Studies targeting this property may be considered as potential therapeutic strategies torespond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma mayinterrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, asseen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs aredue to the immediate and significant disruption of the ascending and descending spinal pathways,which result in varying degrees of motor and sensory impairment. Recent therapeutic studies forSCI have focused on cell transplantation in animal models, using cells capable of inducing axonregeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactoryensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell-based ther-apeutic strategies, there is still little information regarding the mechanisms underlying the successof transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable toachieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulateangiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion.Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both fromanimal models and clinical studies performed on SCI patients, providing promising results for future treatments

Human placenta-derived mesenchymal stem cells stimulate neuronal regeneration by promoting axon growth and restoring neuronal activity

In the last decades, mesenchymal stem cells (MSCs) have become the cornerstone of cellular therapy due to their unique characteristics. Specifically human placenta-derived mesenchymal stem cells (hPMSCs) are highlighted for their unique features, including ease to isolate, non-invasive techniques for large scale cell production, significant immunomodulatory capacity, and a high ability to migrate to injuries. Researchers are exploring innovative techniques to overcome the low regenerative capacity of Central Nervous System (CNS) neurons, with one promising avenue being the development of tailored mesenchymal stem cell therapies capable of promoting neural repair and recovery. In this context, we have evaluated hPMSCs as candidates for CNS lesion regeneration using a skillful co-culture model system. Indeed, we have demonstrated the hPMSCs ability to stimulate damaged rat-retina neurons regeneration by promoting axon growth and restoring neuronal activity both under normoxia and hypoxia conditions. With our model we have obtained neuronal regeneration values of 10%–14% and axonal length per neuron rates of 19-26, μm/neuron. To assess whether the regenerative capabilities of hPMSCs are contact-dependent effects or it is mediated through paracrine mechanisms, we carried out transwell co-culture and conditioned medium experiments confirming the role of secreted factors in axonal regeneration. It was found that hPMSCs produce brain derived, neurotrophic factor (BDNF), nerve-growth factor (NGF) and Neurotrophin-3 (NT-3), involved in the process of neuronal regeneration and restoration of the physiological activity of neurons. In effect, we confirmed the success of our treatment using the patch clamp technique to study ionic currents in individual isolated living cells demonstrating that in our model the regenerated neurons are electrophysiologically active, firing action potentials. The outcomes of our neuronal regeneration studies, combined with the axon-regenerating capabilities exhibited by mesenchymal stem cells derived from the placenta, present a hopeful outlook for the potential therapeutic application of hPMSCs in the treatment of neurological disorders.post-print2885 K

Small molecules fail to induce direct reprogramming of adult rat olfactory ensheathing glia to mature neurons

An approach to generate new neurons after central nervous system injury or disease is direct reprogramming of the individual's own somatic cells into differentiated neurons. This can be achieved either by transduction of viral vectors that express neurogenic transcription factors and/or through induction with small molecules, avoiding introducing foreign genetic material in target cells. In this work, we propose olfactory ensheathing glia (OEG) as a candidate for direct reprogramming to neurons with small molecules due to its well-characterized neuro-regenerative capacity. After screening different combinations of small molecules in different culture conditions, only partial reprogramming was achieved: induced cells expressed neuronal markers but lacked the ability of firing action potentials. Our work demonstrates that direct conversion of adult olfactory ensheathing glia to mature, functional neurons cannot be induced only with pharmacological tools

Cell therapy for spinal cord injury with olfactory ensheathing glia cells (OECs).

The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs). The devastating consequences of SCIs are due to the immediate and significant disruption of the ascending and descending spinal pathways, which result in varying degrees of motor and sensory impairment. Recent therapeutic studies for SCI have focused on cell transplantation in animal models, using cells capable of inducing axon regeneration like Schwann cells (SchCs), astrocytes, genetically modified fibroblasts and olfactory ensheathing glia cells (OECs). Nevertheless, and despite the improvements in such cell‐based therapeutic strategies, there is still little information regarding the mechanisms underlying the success of transplantation and regarding any secondary effects. Therefore, further studies are needed to clarify these issues. In this review, we highlight the properties of OECs that make them suitable to achieve neuroplasticity/neuroregeneration in SCI. OECs can interact with the glial scar, stimulate angiogenesis, axon outgrowth and remyelination, improving functional outcomes following lesion. Furthermore, we present evidence of the utility of cell therapy with OECs to treat SCI, both from animal models and clinical studies performed on SCI patients, providing promising results for future treatments.pre-print48973 K