Stem Cells in Regenerative Medicine

Stem cells constitute a set of undifferentiated cells with the capacity to differentiate into other cell types and to self-renew [...]

Reducing Self-Stigma in People with Severe Mental Illness Participating in a Regular Football League: An Exploratory Study

For the past 15 years, a regular indoor football competition has been taking place in Madrid (Spain) with 15 teams from different mental health services in the city, in which teams face off weekly as part of a competition lasting nine months of the year. We are not aware of whether a similar competition experience is offered in other cities. The purpose of the present study was to evaluate whether participating in this league, called Ligasame, has an influence on participants’ self-stigma. To do so, the Internalized Stigma of Mental Illness scale (ISMI) was adapted into Spanish and applied to 108 mental health patients, 40% of which participated in Ligasame, and the remainder of which did not. The results obtained reflect significant differences between those participating in Ligasame and those that did not in terms of two specific dimensions related to self-stigma (stereotype endorsement and stigma resistance) and total score. On the other hand, no significant differences were found in terms of other variables, such as patients’ prior diagnosis, age or belonging to different resources/associations. In this article, we discuss the importance of these results in relation to reducing self-stigma through participation in a regular yearly mental health football league

Generar “comportamientos inclusivos” como herramienta para operativizar la inclusión

El presente artículo trata de analizar un campo emergente en los nuevos diseños psico-instruccionales desde el punto de vista inclusivo. La incertidumbre y los vertiginosos cambios que se están produciendo en la sociedad en general y en el sistema educativo, en particular durante esta era postmoderna de la llamada cuarta revolución, activan una urgente re-adaptación del comportamiento docente tanto en los sistemas de garantía de calidad como en la práctica diaria desde el nuevo modelo inclusivo de psicología positiva; cuya idea-fuerza subyacente no es otra que permitir un comportamiento auténticamente inclusivo desde la propia voluntariedad de la acción docente, y evitar de esta forma el consiguiente malestar personal y por ende socio-laboral.

Gamma-convergence of equi-coercive nonlinear energies defined on vector-valued functions, with non-uniformly bounded coefficients

The present paper deals with the asymptotic behavior of equi-coercive sequences {Fn} of nonlinear functionals defined over vector-valued functions in W1,p 0 (Ω)M , where p > 1, M ≥ 1, and Ω is a bounded open set of RN , N ≥ 2. The strongly local energy density Fn(·, Du) of the functional Fn satisfies a Lipschitz condition with respect to the second variable, which is controlled by a positive sequence {an} which is only bounded in some suitable space L r(Ω). We prove that the sequence {Fn} Γ-converges for the strong topology of Lp(Ω)M to a functional F which has a strongly local density F(·, Du) for sufficiently regular functions u. This compactness result extends former results on the topic, which are based either on maximum principle arguments in the nonlinear scalar case, or adapted div-curl lemmas in the linear case. Here, the vectorial character and the nonlinearity of the problem need a new approach based on a careful analysis of the asymptotic minimizers associated with the functional Fn. The relevance of the conditions which are imposed to the energy density Fn(·, Du), is illustrated by several examples including some classical hyper-elastic energies.Ministerio de Economía y CompetitividadInstitut de Recherche Mathématique de Renne

Modeling of lactic acid rejection from lactose in acidified cheese whey by nanofiltration

The continuously increasing demand of lactic acid opens a window for the integration of membrane technology in the dairy industry, improving the sustainability by avoiding the use of large amounts of chemicals and waste generation. Lactic acid recovery from fermentation broth without precipitation has been studied by numerous processes. In this work, a commercial membrane with high lactose rejection and a moderate lactic acid rejection, enabling a permselectivity up to 40%, is sought to perform the simultaneous removal of lactic acid and lactose separation from the acidified sweet whey from mozzarella cheese production in a single stage. The AFC30 membrane of the thin film composite nanofiltration (NF) type was selected because of its high negative charge, low isoelectric point, and divalent ion rejection, as well as a lactose rejection higher than 98% and a lactic acid rejection lower than 37%, at pH 3.5, to minimize the need of additional separation steps. The experimental lactic acid rejection was evaluated at varying feed concentration, pressure, temperature, and flow rate. As the dissociation degree of lactic acid is negligible in industrially simulated conditions, the performance of this NF membrane was validated by the irreversible thermodynamic Kedem-Katchalsky and Spiegler-Kedem models, with the best prediction in the latter case, with the parameter values: Lp = 3.24 ± 0.87 L × m-2 × h-1 × bar-1 and = 15.06 ± 3.17 L × m-2 × h-1, and d = 0.45 ± 0.03. The results obtained in this work open the way for the up-scaling of membrane technology on the valorization of dairy effluents by simplifying the operation process and the model prediction and the choice of the membrane.Science and Innovation (Madrid, Spain; MCIN/AEI/10.13039/501100011033) and European Union “NextGenerationEU”/PRTR” under projects CTM2017-87850-R and EIN2020-112319 is gratefully acknowledged

Combination of Biomaterials and Extracellular Vesicles from Mesenchymal Stem-Cells: New Therapeutic Strategies for Skin-Wound Healing

Hard-to-heal chronic wounds associated with aging and high-prevalence pathologies, such as diabetes, are a global health problem. Therefore, it is necessary to advance effective treatments to accelerate wound healing. Among these potential treatments are new therapies based on mesenchymal stem cells (MSC) and their secretomes, including extracellular vesicles (EV). They have an important therapeutic potential for the treatment of chronic ulcers, due to their immunomodulatory activity, as well as their ability to induce angiogenesis, cell proliferation and cell migration. The use of MSC-derived EV in regenerative medicine involves cell-free therapies that decrease risks associated with cell therapies, such as the potential development of tumors. However, the short half-life of MSC-EV is a limitation for their clinical use. A therapeutic strategy to increase the regenerative efficiency of EV in wounds is to encapsulate them in biomaterials. The latter must protect and progressively release EV in damaged tissues, optimizing healing. Biomaterials that can be used include hydrogels. These, in addition to acting as a vehicle for sustained application of EV, can create favorable environments for wound healing. Thus, the aim of this review is to critically describe the latest advances in the development of such therapeutic strategies. It highlights the significance and clinical potential of these new therapies, as well as the need to develop clinical trials, to ascertain their performance

Clinical potential of mesenchymal stem cell-derived exosomes in bone regeneration

Bone metabolism is regulated by osteoblasts, osteoclasts, osteocytes, and stem cells. Pathologies such as osteoporosis, osteoarthritis, osteonecrosis, and traumatic fractures require effective treatments that favor bone formation and regeneration. Among these, cell therapy based on mesenchymal stem cells (MSC) has been proposed. MSC are osteoprogenitors, but their regenerative activity depends in part on their paracrine properties. These are mainly mediated by extracellular vesicle (EV) secretion. EV modulates regenerative processes such as inflammation, angiogenesis, cell proliferation, migration, and differentiation. Thus, MSC-EV are currently an important tool for the development of cell-free therapies in regenerative medicine. This review describes the current knowledge of the effects of MSC-EV in the different phases of bone regeneration. MSC-EV has been used by intravenous injection, directly or in combination with different types of biomaterials, in preclinical models of bone diseases. They have shown great clinical potential in regenerative medicine applied to bone. These findings should be confirmed through standardization of protocols, a better understanding of the mechanisms of action, and appropriate clinical trials. All that will allow the translation of such cell-free therapy to human clinic applications

Flavonoid Phloretin Inhibits Adipogenesis and Increases OPG Expression in Adipocytes Derived from Human Bone-Marrow Mesenchymal Stromal-Cells

Phloretin (a flavonoid abundant in apple), has antioxidant, anti-inflammatory, and glucose-transporter inhibitory properties. Thus, it has interesting pharmacological and nutraceutical potential. Bone-marrow mesenchymal stem cells (MSC) have high differentiation capacity, being essential for maintaining homeostasis and regenerative capacity in the organism. Yet, they preferentially differentiate into adipocytes instead of osteoblasts with aging. This has a negative impact on bone turnover, remodeling, and formation. We have evaluated the effects of phloretin on human adipogenesis, analyzing MSC induced to differentiate into adipocytes. Expression of adipogenic genes, as well as genes encoding OPG and RANKL (involved in osteoclastogenesis), protein synthesis, lipid-droplets formation, and apoptosis, were studied. Results showed that 10 and 20 µM phloretin inhibited adipogenesis. This effect was mediated by increasing beta-catenin, as well as increasing apoptosis in adipocytes, at late stages of differentiation. In addition, this chemical increased OPG gene expression and OPG/RANKL ratio in adipocytes. These results suggest that this flavonoid (including phloretin-rich foods) has interesting potential for clinical and regenerative-medicine applications. Thus, such chemicals could be used to counteract obesity and prevent bone-marrow adiposity. That is particularly useful to protect bone mass and treat diseases like osteoporosis, which is an epidemic worldwide

Upregulation of NKG2D ligands impairs hematopoietic stem cell function in Fanconi anemia

Cellular immune response; Immunology; Stem cellsRespuesta inmune celular; Inmunología; Células madreResposta immune cel·lular; Immunologia; Cèl·lules mareFanconi anemia (FA) is the most prevalent inherited bone marrow failure (BMF) syndrome. Nevertheless, the pathophysiological mechanisms of BMF in FA have not been fully elucidated. Since FA cells are defective in DNA repair, we hypothesized that FA hematopoietic stem and progenitor cells (HSPCs) might express DNA damage–associated stress molecules such as natural killer group 2 member D ligands (NKG2D-Ls). These ligands could then interact with the activating NKG2D receptor expressed in cytotoxic NK or CD8+ T cells, which may result in progressive HSPC depletion. Our results indeed demonstrated upregulated levels of NKG2D-Ls in cultured FA fibroblasts and T cells, and these levels were further exacerbated by mitomycin C or formaldehyde. Notably, a high proportion of BM CD34+ HSPCs from patients with FA also expressed increased levels of NKG2D-Ls, which correlated inversely with the percentage of CD34+ cells in BM. Remarkably, the reduced clonogenic potential characteristic of FA HSPCs was improved by blocking NKG2D–NKG2D-L interactions. Moreover, the in vivo blockage of these interactions in a BMF FA mouse model ameliorated the anemia in these animals. Our study demonstrates the involvement of NKG2D–NKG2D-L interactions in FA HSPC functionality, suggesting an unexpected role of the immune system in the progressive BMF that is characteristic of FA.This work was supported by the “Ministerio de Ciencia e Innovación y Competitividad y Fondo Europeo de Desarrollo Regional (FEDER)” (SAF2015-68073-R, SAF2015-64152-R, and RTI2018-097125-B-I00); Next Generation EU; Plan de Recuperación Transformación y Resilencia (Instituto de Salud Carlos III; TERAV) (RD12/0019/0023); Programs of the European Commission (HEALTHF5-2012-305421 and EUROFANCOLEN); the “Ministerio de Sanidad, Servicios Sociales e Igualdad” (EC11/060 and EC11/550 “Comunidad de Madrid” (AvanCell, B2017/BMD-3692); and the ICREA-Academia program

Non-specific inhibition of dipeptidyl peptidases 8/9 by dipeptidyl peptidase 4 inhibitors negatively affects mesenchymal stem cell differentiation

DPP4 may play a relevant role in MSC differentiation into osteoblasts or adipocytes. Dipeptidyl peptidase 4 (DPP4) inhibitors (DPP4i), such as sitagliptin and vildagliptin, are used as antidiabetic drugs. However, vildagliptin is not a specific DPP4i and also inhibits DPP8/9, which is involved in energy metabolism and immune regulation. The aim of this study is to evaluate how sitagliptin, vildagliptin or 1G244 (a DPP8/9 specific inhibitor) may influence cell viability, as well as osteogenic and adipogenic differentiation in human mesenchymal stem cells (MSC). Viability, apoptosis, osteoblastogenesis and adipogenesis markers, as well as protein synthesis of β-catenin, were studied in MSC cultures induced to differentiate into osteoblasts or adipocytes in the presence or absence of sitagliptin, vildagliptin or 1G244. The two tested DPP4i did not affect MSC viability, but 1G244 significantly decreased it in MSC and osteoblast-induced cells. Additionally, 1G244 and vildagliptin inhibited osteogenesis and adipogenesis, unlike sitagliptin. Therefore, inhibition of DPP4 did not affect MSC viability and differentiation, whereas inhibition of DPP8/9 negatively affected MSC. To the best of our knowledge, these results show for the first time that DPP8/9 have an important role in the viability and differentiation of human MSC. This data can be considered for human clinical use of drugs affecting DPP8/9 activity