Biocompatible Bacterial Cellulose-Poly(2-hydroxyethyl methacrylate) Nanocomposite Films

A series of bacterial cellulose-poly(2-hydroxyethyl methacrylate) nanocomposite films was prepared by in situ radical polymerization of 2-hydroxyethyl methacrylate (HEMA), using variable amounts of poly(ethylene glycol) diacrylate (PEGDA) as crosslinker. Thin films were obtained, and their physical, chemical, thermal, and mechanical properties were evaluated. The films showed improved translucency compared to BC and enhanced thermal stability and mechanical performance when compared to poly(2-hydroxyethyl methacrylate) (PHEMA). Finally, BC/PHEMA nanocomposites proved to be nontoxic to human adipose-derived mesenchymal stem cells (ADSCs) and thus are pointed as potential dry dressings for biomedical applications

Partnership between platelet-rich plasma and mesenchymal stem cells: in vitro experience

We aim to identify current in vitro research exploring platelet-rich plasma (PRP) effects in human Mesenchymal Stem Cells (MSCs) that may encourage or limit the clinical application of MSCs along with PRP. After a systematic search, we identified 57 in vitro studies, focused on optimization of MSC manufacturing, and expanding knowledge about how PRP modifies MSCs behavior for translational purposes. Influences of PRP on proliferation, migration, stemness, preservation of MSC immune-modulatory properties and appearance of senescence phenotype have been explored. Overall PRP stimulates MSC proliferation, preserves MSCs multipotency and does not interfere with any lineage differentiation. PRP (as platelet lysate or releasate) preserves the immune-privileged potential of MSCs and may delay the appearance of the senescent phenotype. Currently there are few data linking precise molecules and biological mechanisms. Various gaps of knowledge need to be addressed in order to obtain enough useful information for translational purpose

Investigación pre-clínica in vitro en terapias biológicas aplicadas a patología tendinosa.

165 p.Hoy en día, las patologías de tendón o tendinopatías suponen una gran parte de las lesiones del aparato locomotor y se asocian tanto a actividad deportiva como laboral. Los tratamientos actuales para tendinopatías son paliativos y de eficacia limitada. La traslación a la práctica clínica de la terapia regenerativa conocida como plasma rico en plaquetas (PRP) se ha realizado muy rápidamente, principalmente debido a su carácter autólogo que lo convierte en un tratamiento seguro. Sin embargo muchos aspectos biológicos del PRP no se conocen suficientemente y la escasa optimización de los tratamientos hace que su eficacia clínica en Traumatología y Medicina del Deporte siga siendo controvertida. El objetivo general de esta tesis es explorar el potencial terapéutico del PRP en modelos celulares, en distintas situaciones biológicas con repercusión clínica directa, asimismo, estudiar la posible combinación de PRP con terapia celular para lesiones severas en las que el tratamiento con PRP no es suficiente. Así, utilizando modelos celulares in vitro, se estudió el efecto del PRP en la inflamación (artículo I), se desarrolló un modelo de cultivo de células de tendón en 3D (artículo II), se buscó desarrollar la formulación de PRP idónea para cada situación clínica (artículo III), y se estudió la combinación de PRP con 3 tipos de células candidatas para identificar el tratamiento más idóneo para aplicar en tendinopatías severas (artículo IV). Tras estos estudios, se observó que tanto el PRP (conjunto de moléculas de señalización celular) como las células adultas expandidas ¿ex vivo¿ intervienen en los procesos de reparación tendinosa para potenciar los procesos de migración, proliferación celular y angiogénesis y para modular los procesos inflamatorios y la síntesis de matriz extracelular.Asimismo hemos mostrado que la formulación de PRP así como la fuente celular son factores importantes en el diseño de terapias biológicas para la regeneración tendinosa

Angiogenic and innate immune responses triggered by PRP in tendon cells are not modified by hyperuricemia

Background: hyperuricemia is becoming a critical medical problem, and a current focus of research. Uric acid is also a death cell associated stressor that may trigger innate immune responses via the synthesis of inflammatory and angiogenic proteins. Purpose: to investigate the angiogenic/inflammatory protein profile of tendon cells treated with Platelet Rich Plasma (PRP), and to assess if there are any differences in synthesis of angiogenic/inflammatory cytokines between PRP-treated or hyperuricemic PRP-treated cells. Methods: tendon cells were treated with PRP or hyperuricemic PRP and cell culture supernatants examined using glass based protein arrays for inflammation and angiogenesis. Relevant proteins were subsequently quantified by ELISA or EASIA methods. Results: the impact of PRP on angiogenesis and inflammation is evidenced by relevant cytokine synthesis including: Monocyte Chemoattractant Protein (MCP-1/CCL2), Regulated upon Activation Normally T cells Expressed and Secreted (RANTES/CCL5), IL-6/CXCL6, IL-8/CXCL8, Vascular Endothelial Growth Factor (VEGF), Growth Regulated Protein (GRO-a/CXCL1) and Hepatocyte Growth Factor (HGF). IL-1beta was not detected in these conditions. Taken together these data suggest an initial angiogenetic and innate immune responses driven by chemokines that is not altered by the presence of hyperuricemia, at this point, except for IL-8 secretion, p= 0.042

IBRORS-MCL study: a Spanish retrospective and observational study of relapsed/refractory mantle-cell lymphoma treated with ibrutinib in routine clinical practice

This retrospective study evaluated 66 patients diagnosed with relapsed and/or refractory mantle cell lymphoma (R/R MCL) treated with ibrutinib in Spain in routine clinical practice. At diagnosis, patients had a median age of 64.5 years, 63.6% presented with intermediate/high sMIPI (simplified prognostic index for advanced-stage mantle cell lymphoma), 24.5% had the blastoid variant, and 55.6% had a Ki67 > 30%. Patients had received a median of 2 prior lines of therapy (range 1-2; min-max 1-7). Overall response rate was 63.5%, with 38.1% of patients achieving complete response (CR). With a median duration of ibrutinib exposure of 10.7 months (range 5.2-19.6; min-max 0.3-36), the median progression-free survival (PFS) and overall survival (OS) were 20 months [95% confidence interval (CI) 8.8-31.1] and 32 months (95% CI 22.6-41.3), respectively, and were not reached in patients achieving CR. No grade ≥ 3 cardiovascular toxicity or bleeding was reported. This study supports that treatment with ibrutinib leads to high response rates and favorable survival outcomes in patients with R/R MCL

Biocompatible Bacterial Cellulose-Poly(2-hydroxyethyl methacrylate) Nanocomposite Films

A series of bacterial cellulose-poly(2-hydroxyethyl methacrylate) nanocomposite films was prepared by in situ radical polymerization of 2-hydroxyethyl methacrylate (HEMA), using variable amounts of poly(ethylene glycol) diacrylate (PEGDA) as cross-linker. Thin films were obtained, and their physical, chemical, thermal, and mechanical properties were evaluated. The films showed improved translucency compared to BC and enhanced thermal stability and mechanical performance when compared to poly(2-hydroxyethyl methacrylate) (PHEMA). Finally, BC/PHEMA nanocomposites proved to be nontoxic to human adipose-derived mesenchymal stem cells (ADSCs) and thus are pointed as potential dry dressings for biomedical applications

IBRORS-MCL study: a Spanish retrospective and observational study of relapsed/refractory mantle-cell lymphoma treated with ibrutinib in routine clinical practice.

This retrospective study evaluated 66 patients diagnosed with relapsed and/or refractory mantle cell lymphoma (R/R MCL) treated with ibrutinib in Spain in routine clinical practice. At diagnosis, patients had a median age of 64.5 years, 63.6% presented with intermediate/high sMIPI (simplified prognostic index for advanced-stage mantle cell lymphoma), 24.5% had the blastoid variant, and 55.6% had a Ki67 > 30%. Patients had received a median of 2 prior lines of therapy (range 1-2; min-max 1-7). Overall response rate was 63.5%, with 38.1% of patients achieving complete response (CR). With a median duration of ibrutinib exposure of 10.7 months (range 5.2-19.6; min-max 0.3-36), the median progression-free survival (PFS) and overall survival (OS) were 20 months [95% confidence interval (CI) 8.8-31.1] and 32 months (95% CI 22.6-41.3), respectively, and were not reached in patients achieving CR. No grade ≥ 3 cardiovascular toxicity or bleeding was reported. This study supports that treatment with ibrutinib leads to high response rates and favorable survival outcomes in patients with R/R MCL