Artículos de revista (CUN)
Permanent URI for this collectionhttps://hdl.handle.net/10171/70263
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- Corrigendum: Cost-effective, safe, and personalized cell therapy for critical limb ischemia in type 2 diabetes mellitus (vol 10, 1151, 2019)(Frontiers Media, 2020) Bedoya, F.J. (Francisco J.); Soria, B. (Bernat); Hmadcha, A. (Abdelkrim); Aguilera, Y. (Yolanda); Tejedo, J.R. (Juan R.); Juan, V. (Verónica); Soria-Juan, B. (Bárbara); Martinez-de-la-Cuesta, A. (Antonio); Llanos, L. (Lucía); Andreu, E.J. (Enrique José); Sackstein, R. (Robert); Castellanos, G. (Gregorio); Garcia-Olmos, D. (Damián); Miralles, M. (Manuel); Lozano, F.S. (Francisco S.); Capilla-González, V. (Vivian); Martín, F. (Franz); Prosper-Cardoso, F. (Felipe); Ruiz-Salmerón, R. (Rafael); García-Arranz, M. (Mariano); Moraleda, J. M. (José M.); Grochowicz, L. (Lukasz); Escacena, N. (Natalia); Sanchez-Guijo, F.M. (Fermín M.); Río-Solá, L. (Lourdes) delReference 86 was also included as “Escacena N. Cellular medication as a therapeutic alternative in chronic critical limb ischemia in diabetic patients without the possibility of revascularization. Dissertation Thesis. Sevilla Spain: University of Sevilla. (2016)”. This reference should be included as number 107 “Escacena N. Cellular medication as a therapeutic alternative in chronic critical limb ischemia in diabetic patients without the possibility of revascularization (Dissertation Thesis). University of Sevilla, Seville, Spain (2016).”
- Haematopoietic stem cell transplantation in adult soft-tissue sarcoma: an analysis from the European Society for Blood and Marrow Transplantation(2020) Secondino, S. (Simona); Korenbaum, C. (Clément); Koehl, U. (Ulrike); Fröhling, S. (Stefan); Krüger, W. (William); Nicolas-Virelizier, E. (Emmanuelle); Santoro, A. (Armando); Rifon, J. J. (Jose J.); Passweg, J.R. (Jakob R.); Dreger, P. (Peter); Heinz, J. (Jürgen); Pedrazzoli, P. (Paolo); Labopin, M. (Myriam); Badoglio, M. (Manuela); Di-Nicola, M. (Massimo); Siena, S. (Salvatore); Blaise, D. (Didier); Verbeek, M. (Mareike); Chabannon, C. (Christian); Heilig, C.E. (Christoph E.)Background The role of high-dose chemotherapy with autologous stem cell transplantation (ASCT) in the treatment of soft-tissue sarcoma (STS) remains an unsettled issue. Prospective clinical trials failed to prove a benefit of the procedure but were limited by small and heterogeneous patient cohorts. Thus, it is unknown if ASCT may be a valuable treatment option in specific patient subgroups. Methods The purpose of this study was to investigate the value of ASCT according to histological subtype in STS patients who were registered in the European Society for Blood and Marrow Transplantation database between 1996 and 2016. Results Median progression-free (PFS) and overall survival (OS) in the entire cohort of 338 patients were 8.3 and 19.8 months, respectively, and PFS and OS at 5 years were 13% and 25%, respectively. Analysis of outcomes in different subgroups showed that younger age, better remission status before transplantation and melphalanbased preparative regimen were predictive of benefit from ASCT, whereas histology and grading had no statistically significant impact. Conclusions Outcomes after ASCT compared favorably to those of recent trials on conventional chemotherapies and targeted therapies in STS, including histology-tailored approaches. ASCT, thus, should be reinvestigated in clinical trials focusing on defined patient subgroups.
- Vacuna idiotípica en el tratamiento del linfoma folicular: situación actual y perspectivas futuras(2009) Tañá-Rivero, P. (Pedro); Lopez-Diaz-de-Cerio, A. (Ascensión); Inoges, S. (Susana); Villanueva, H. (Helena); Bendandi, M. (Maurizio); Soria, E. (Elena); Zabalegui, N. (Natalia)El linfoma folicular (LF) está considerado como el segundo tipo de linfoma no-Hodgkin más común, representando más del 20% del total de los linfomas. Es una enfermedad de progresión lenta y curso indolente en la que, a pesar de la buena respuesta al tratamiento, las recaídas son muy frecuentes y cada vez es más difícil conseguir respuestas completas. Por ello, se puede considerar que hasta el momento, el LF es incurable. La búsqueda continua de nuevas estrategias terapéuticas en enfermedades neoplásicas, junto con un mejor conocimiento del sistema inmunitario, ha llevado a la aparición de una nueva disciplina, conocida con el nombre de inmunoterapia, que aprovecha la capacidad del sistema inmunitario de atacar lo extraño sin dañar lo propio. El LF es un tumor muy apropiado para este tipo de tratamiento por presentar un antígeno específico de tumor: el idiotipo de la inmunoglobulina monoclonal expresada en la membrana de todas las células tumorales. Se han realizado diversos estudios en los que se ha probado la inmunoterapia como tratamiento complementario al tratamiento convencional. Recientemente, nuestro grupo ha publicado un estudio en el que se observa claramente que los resultados que se obtienen tras la vacunación idiotípica, cuando se consigue la inmunización adecuada del paciente, son mejores que los obtenidos con quimioterapia sola. En este sentido, es necesario seguir investigando para aclarar si la vacunación idiotípica pudiera no sólo mantener remisiones completas duraderas en los pacientes vacunados, sino incluso conseguir la curación de los mismos. Por ello, resulta interesante abordar un mejor planteamiento de los ensayos clínicos, la mejora de la producción de la vacuna y el estudio de mecanismos de la célula tumoral capaces de modificar la inmunoglobulina específica del tumor.
- Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: long-term follow up of a multicenter randomized controlled clinical trial (phase I/II)(BMC, 2018) Cañizo, C. (C.) del; Granero-Moltó, F. (Froilán); Bondia, J.M. (J. M.); Aquerreta, D. (Dámaso); López-Elío, S. (Silvia); Villarón, E. (Eva); Mora, G. (Gonzalo); Andreu, E.J. (Enrique José); Blanco, J.F. (J. F.); Valentí-Nin, J.R. (Juan Ramón); Prosper-Cardoso, F. (Felipe); Nuñez-Cordoba, J.M. (Jorge M.); Lamo-Espinosa, J.M. (J. M.); Sanchez-Guijo, F.M. (Fermín M.); Valentí-Azcárate, A. (Andrés)Background: Mesenchymal stromal cells (MSCs) are a promising option to treat knee osteoarthritis (OA). Their safety and usefulness have been reported in several short-term clinical trials but less information is available on the longterm efects of MSC in patients with osteoarthritis. We have evaluated patients included in our previous randomized clinical trial (CMM-ART, NCT02123368) to determine their long-term clinical efect. Materials: A phase I/II multicenter randomized clinical trial with active control was conducted between 2012 and 2014. Thirty patients diagnosed with knee OA were randomly assigned to Control group, intraarticularly administered hyaluronic acid alone, or to two treatment groups, hyaluronic acid together with 10×106 or 100×106 cultured autol‑ ogous bone marrow-derived MSCs (BM-MSCs), and followed up for 12 months. After a follow up of 4 years adverse efects and clinical evolution, assessed using VAS and WOMAC scorings are reported. Results: No adverse efects were reported after BM-MSCs administration or during the follow-up. BM-MSCs-adminis‑ tered patients improved according to VAS, median value (IQR) for Control, Low-dose and High-dose groups changed from 5 (3, 7), 7 (5, 8) and 6 (4, 8) to 7 (6, 7), 2 (2, 5) and 3 (3, 4), respectively at the end of follow up (Low-dose vs Control group, p=0.01; High-dose vs Control group, p=0.004). Patients receiving BM-MSCs also improved clinically accord‑ ing to WOMAC. Control group showed an increase median value of 4 points (−11;10) while Low-dose and Highdose groups exhibited values of −18 (−28;−9) and −10 (−21;−3) points, respectively (Low-dose vs Control group p=0.043). No clinical diferences between the BM-MSCs receiving groups were found. Conclusions: Single intraarticular injection of in vitro expanded autologous BM-MSCs is a safe and feasible proce‑ dure that results in long-term clinical and functional improvement of knee OA.
- Preclinical evaluation of a cell-based gene therapy using the sleeping beauty transposon system in choroidal neovascularization(Elsevier BV, 2019) Ivics, Z. (Zoltán); Garcia-Garcia, L. (Laura); Marie, C. (Corinne); Johnen, S. (S.); Rodriguez-Madoz, J.R. (Juan Roberto); Scherman, D. (Daniel); Pouillot, S. (Severine); Garcia-Layana, A. (Alfredo); Izsvák, Z. (Zsuzsanna); Thumann, G. (Gabriele); Diarra, S. (Sabine); Bezunartea, J. (Jaione); Miskey, C. (Csaba); Fernandez-Robredo, P. (Patricia); Sebe, A. (Attila); Prosper-Cardoso, F. (Felipe); Kropp, M. (Martina); Hernandez, M. (María); Recalde, S. (Sergio)Age-related macular degeneration (AMD) is a progressive retinal disorder characterized by imbalanced pro- and antiangiogenic signals. The aim of this study was to evaluate the effect of ex vivo cell-based gene therapy with stable expression of human pigment epithelium-derived factor (PEDF) release using the non-viral Sleeping Beauty (SB100X) transposon system delivered by miniplasmids free of antibiotic resistance markers (pFAR4). Retinal pigment epithelial (RPE) cells and iris pigment epithelial (IPE) cells were co-transfected with pFAR4-inverted terminal repeats (ITRs) CMV-PEDF-BGH and pFAR4-CMV-SB100X-SV40 plasmids. Laser-induced choroidal neovascularization (CNV) was performed in rats, and transfected primary cells (transfected RPE [tRPE] and transfected IPE [tIPE] cells) were injected into the subretinal space. The leakage and CNV areas, vascular endothelial growth factor (VEGF), PEDF protein expression, metalloproteinases 2 and 9 (MMP-2/9), and microglial/macrophage markers were measured. Injection with tRPE/IPE cells significantly reduced the leakage area at 7 and 14 days and the CNV area at 7 days. There was a significant increase in PEDF and the PEDF/VEGF ratio with tRPE cells and a reduction in the MMP-2 activity. Our data demonstrated that ex vivo non-viral gene therapy reduces CNV and could be an effective and safe therapeutic option for angiogenic retinal diseases.
- Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice(Wiley, 2021) Calvo, I.A. (Isabel A.); Granero-Moltó, F. (Froilán); Paramo, J.A. (José Antonio); Ripalda-Cemboráin, P. (Purificación); Montiel-Terrón, V. (Verónica); Aldazabal, J. (Javier); Orbe, J. (Josune); Rodriguez, J.A. (José Antonio); Lopez, T. (Tania); Valdés-Fernández, J. (José); Muiños-López, E. (Emma); Romero-Torrecilla, J.A. (Juan Antonio); Prosper-Cardoso, F. (Felipe); Saez, B. (Borja)The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion
- Catheter-based intramyocardial injection of FGF1 or NRG1-loaded MPs improves cardiac function in a preclinical model of ischemia-reperfusion(Nature Publishing Group, 2016) Garcia-de-Yebenes, M. (Manuel); Blanco-Prieto, M.J. (María José); Gavira, J.J. (Juan José); Garbayo, E; Prosper-Cardoso, F. (Felipe); Pelacho, B. (Beatriz); Lana, H. (Hugo); Abizanda-Sarasa, G. (Gloria)Cardiovascular protein therapeutics such as neuregulin (NRG1) and acidic-fibroblast growth factor (FGF1) requires new formulation strategies that allow for sustained bioavailability of the drug in the infarcted myocardium. However, there is no FDA-approved injectable protein delivery platform due to translational concerns about biomaterial administration through cardiac catheters. We therefore sought to evaluate the efficacy of percutaneous intramyocardial injection of poly(lactic-co-glycolic acid) microparticles (MPs) loaded with NRG1 and FGF1 using the NOGA MYOSTAR injection catheter in a porcine model of ischemia-reperfusion. NRG1- and FGF1-loaded MPs were prepared using a multiple emulsion solvent-evaporation technique. Infarcted pigs were treated one week after ischemiareperfusion with MPs containing NRG1, FGF1 or non-loaded MPs delivered via clinically-translatable percutaneous transendocardial-injection. Three months post-treatment, echocardiography indicated a significant improvement in systolic and diastolic cardiac function. Moreover, improvement in bipolar voltage and decrease in transmural infarct progression was demonstrated by electromechanical NOGA-mapping. Functional benefit was associated with an increase in myocardial vascularization and remodeling. These findings in a large animal model of ischemia-reperfusion demonstrate the feasibility and efficacy of using MPs as a delivery system for growth factors and provide strong evidence to move forward with clinical studies using therapeutic proteins combined with catheter-compatible biomaterials.
- Polymeric electrospun scaffolds: neuregulin encapsulation and biocompatibility studies in a model of myocardial ischemia(Mary Ann Liebert, 2015) Heffels K.H. (Karl‐Heinz); Groll, J. (Jürgen); Blanco-Prieto, M.J. (María José); Rossi, A. (Ángela); Prosper-Cardoso, F. (Felipe); Simon-Yarza, T. (Teresa)Cardiovascular disease represents one of the major health challenges in modern times and is the number one cause of death globally. Thus, numerous studies are under way to identify effective cell‐ and/or growth factor‐based therapies for repairing damaged cardiac tissue. In this regard, improving the engraftment or survival of regenerative cells and prolonging growth factor exposure have become fundamental goals in advancing these therapeutic approaches. Biomaterials have emerged as innovative scaffolds for the delivery of both cells and proteins in tissue engineering applications. In the present study, electrospinning was used to generate smooth homogenous polymeric fibers, which consisted of a PLGA/NCO‐sP(EO‐stat‐PO) polymer blend encapsulating the cardioactive growth factor, Neuregulin‐1 (Nrg). We evaluated the biocompatibility and degradation of this Nrg‐containing biomaterial in a rat model of myocardial ischemia. Histological analysis revealed the presence of an initial acute inflammatory response after implantation, which was followed by a chronic inflammatory phase, characterized by the presence of giant cells. Notably, the scaffold remained in the heart after 3 months. Furthermore, an increase in the M2:M1 macrophage ratio following implantation suggested the induction of constructive tissue remodeling. Taken together, the combination of Nrg‐encapsulating scaffolds with cells capable of inducing cardiac regeneration could represent an ambitious and promising therapeutic strategy for repairing diseased or damaged myocardial tissue.
- Generation and characterization of human iPSC line generated from mesenchymal stem cells derived from adipose tissue(Elsevier, 2016) Rodriguez-Madoz, J.R. (Juan Roberto); Rodriguez, S. (Saray); Andreu, E.J. (Enrique José); Barajas, M. (Miguel); Mazo, M. (Manuel); Prosper-Cardoso, F. (Felipe); Abizanda-Sarasa, G. (Gloria); Zapata-Linares, N.M. (Natalia María)Abstract In this work, mesenchymal stem cells derived from adipose tissue (ADSCs) were used for the generation of the human-induced pluripotent stem cell line G15.AO. Cell reprogramming was performed using retroviral vectors containing the Yamanaka factors, and the generated G15.AO hiPSC line showed normal karyotype, silencing of the exogenous reprogramming factors, induction of the typical pluripotency-associated markers, alkaline phosphatase enzymatic activity, and in vivo and in vitro differentiation ability to the three germ layers.
- Molecular and cellular basis for immunomodulation with monoclonal antibodies(BioMed Central, 2015) Melero, I. (Ignacio)