Foundation Eduardo Anitua

Gasteiz / Vitoria, Spain

Foundation Eduardo Anitua

Gasteiz / Vitoria, Spain

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Anitua E.,Foundation Eduardo Anitua | Pascual C.,Institute Investigacion Hospital 12 Of Octubre I12 | Pascual C.,CIBER ISCIII | Antequera D.,Institute Investigacion Hospital 12 Of Octubre I12 | And 7 more authors.
Neurobiology of Aging | Year: 2014

Impaired growth factor function is thought to drive many of the alterations observed in Alzheimer's disease (AD) patients. Endogenous regenerative technology, PRGF (plasma rich in growth factor)-Endoret, is designed for the delivery of a complex pool of patient's own active morphogens that may stimulate tissue regeneration. We obtained and characterized PRGF-Endoret preparations from human blood. We used, as experimental approach invivo, APP/PS1 mice, characterized by age-dependent brain amyloid-β (Aβ) accumulation. Intranasal administration of PRGF-Endoret to APP/PS1 mice resulted in an important decrease in brain Aβ deposition and tau phosphorylation. PRGF-Endoret-treated APP/PS1 mice also showed decreased astrocyte reactivity, and prevented protein synaptic loss. Invitro approaches demonstrated that PRGF-Endoret treatment modulated astrocyte activation, reducing inflammatory responses, and promoted Aβ degradation. Furthermore, PRGF-Endoret stimulated global improvements in anxiety, learning, and memory behaviors. Our findings show that PRGF-Endoret exerts multifunctional and complementary effects that result in the reversal of the broad range of cognitive deficits in AD, suggesting that PRGF-Endoret may hold promise as an innovative therapy in AD. © 2014 Elsevier Inc.


Sanchez M.,Arthroscopic Surgery Unit | Yoshioka T.,Arthroscopic Surgery Unit | Yoshioka T.,University of Tsukuba | Ortega M.,Galdakao Usansolo Hospital | And 2 more authors.
Knee Surgery, Sports Traumatology, Arthroscopy | Year: 2014

Purpose: Peroneal nerve palsy in traumatic knee dislocations associated with multiple ligament injuries is common. Several surgical approaches are described for this lesion with less-than-optimal outcomes. The present case represents the application of plasma rich in growth factors (PRGF) technology for the treatment of peroneal nerve palsy with drop foot. This technology has already been proven its therapeutic potential for various musculoskeletal disorders. Based on these results, we hypothesized that PRGF could stimulate the healing process of traumatic peroneal nerve palsy with drop foot. Methods: The patient was a healthy 28-year-old man. He suffered peroneal nerve palsy with drop foot after multiple ligament injuries of the knee. PRGF was prepared according to the manufactured instruction. Eleven months after the trauma with severe axonotmesis, serial intraneural infiltrations of PRGF were started using ultrasound guidance. The therapeutic effect was assessed by electromyography (EMG), echogenicity of the peroneal nerve under ultrasound (US) and manual muscle testing. Results: Twenty-one months after the first injection, not complete but partial useful recovery is obtained. He is satisfied with walking and running without orthosis. Sensitivity demonstrates almost full recovery in the peroneal nerve distribution area. EMG controls show complete reinnervation for the peroneus longus and a better reinnervation for the tibialis anterior muscle, compared with previous examinations. Conclusion: Plasma rich in growth factors (PRGF) infiltrations could enhance healing process of peroneal nerve palsy with drop foot. This case report demonstrates the therapeutic potential of this technology for traumatic peripheral nerve palsy and the usefulness of US-guided PRGF. Level of evidence: V. © 2013 Springer-Verlag Berlin Heidelberg.


PubMed | Biotechnology Institute BTI, Foundation Medicine and Foundation Eduardo Anitua
Type: Journal Article | Journal: PloS one | Year: 2015

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions.


PubMed | Eduardo Anitua Foundation
Type: | Journal: Current pharmaceutical biotechnology | Year: 2016

Ultraviolet irradiation is able to deeply penetrate into the dermis and alter fibroblast structure and function, leading to a degradation of the dermal extracellular matrix.The regenerative effect of plasma rich in growth factors (PRGF) on skin ageing was investigated using UVB photo-stressed human dermal fibroblasts as an in vitro culture model.PRGF was assessed over the main indicative features of ultraviolet B irradiation, including ROS formation, cell viability and death detection, apoptosis/necrosis analysis and biosynthetic activity measurement. Four different UV irradiation protocols were tested in order to analyze the beneficial effects of PRGF.Ultraviolet irradiation exhibited a dose dependent cytotoxicity and dose of 400mJ/cm2 was selected for subsequent experiments. PRGF increased the cell viability and decreased the cell death comparing to the non-treated group. The apoptosis and necrosis were significantly lower in PRGF treated fibroblasts. ROS production after UV irradiation was significantly reduced in the presence of PRGF. Procollagen type I, hyaluronic acid and TIMP-1 levels were higher in the when treated with PRGF.This preliminary in vitro study suggests that PRGF is able to prevent UVB derived photo-oxidative stress and to diminish the cell damage caused by ultraviolet irradiation.


Anitua E.,Foundation Eduardo Anitua | Anitua E.,Biotechnology Institute BTI | Zalduendo M.,Biotechnology Institute BTI | Troya M.,Biotechnology Institute BTI | And 2 more authors.
PLoS ONE | Year: 2015

One of the main differences among platelet-rich plasma (PRP) products is the inclusion of leukocytes that may affect the biological efficacy of these autologous preparations. The purpose of this study was to evaluate whether the addition of leukocytes modified the morphological, biomechanical and biological properties of PRP under normal and inflammatory conditions. The release of pro-inflammatory cytokines from plasma rich in growth factors (PRGF) and leukocyte-platelet rich plasma (L-PRP) scaffolds was determined by enzyme-linked immunosorbent assay (ELISA) and was significantly increased under an inflammatory condition when leukocytes were included in the PRP. Fibroblasts and osteoblasts treated with L-PRP, under an inflammatory situation, underwent a greater activation of NFκB pathway, proliferated significantly less and secreted a higher concentration of pro-inflammatory cytokines. These cellular events were assessed through Western blot and fluorimetric and ELISA methods, respectively. Therefore, the inclusion of leukocytes induced significantly higher pro-inflammatory conditions. © 2015 Anitua et al.


Sanchez M.,Hospital Vithas San Jose | Anitua E.,Biotechnology Institute BTI Vitoria | Anitua E.,Foundation Eduardo Anitua | Delgado D.,Hospital Vithas San Jose | And 4 more authors.
Injury | Year: 2014

Muscle injuries account for between 10% and 55% of all sporting injuries. Although the skeletal muscle is a plastic organ capable of responding efficiently to environmental changes, the appropriate treatment of muscle injuries remains a daunting clinical challenge in sports medicine. There is considerable evidence to indicate that growth factors, such as transforming growth factor-β (TGFβ), hepatocyte growth factor (HGF) or insulin-like growth factor (IGF), and fibrin matrix are key in cellular events required for muscle repair and regeneration, namely myogenesis, angiogenesis and fibrogenesis. An innovative biological approach to the treatment of muscle injuries is the application of Plasma Rich in Growth Factors (PRGF) in intramuscular infiltrations. PRGF delivers growth factors, cytokines and adhesive proteins present in platelets and plasma, as well as other biologically-active proteins conveyed by the plasma, such as fibrinogen, prothrombin and fibronectin. This autologous, mimetic biomaterial embedded with a pool of growth factors acts as a smart dynamic scaffold, and should be applied taking into account a biological approach. A clinical trial is required to assess the functional repair outcome of PRGF infiltrations in muscle injuries. © 2014 Elsevier Ltd. All rights reserved.


Anitua E.,Foundation Eduardo Anitua | Zalduendo M.M.,Foundation Eduardo Anitua | Prado R.,Foundation Eduardo Anitua | Alkhraisat M.H.,Foundation Eduardo Anitua | Orive G.,Foundation Eduardo Anitua
Journal of Biomedical Materials Research - Part A | Year: 2015

The potential influence of leukocyte incorporation in the kinetic release of growth factors from platelet-rich plasma (PRP) may explain the conflicting efficiency of leukocyte platelet-rich plasma (L-PRP) scaffolds in tissue regeneration. To assess this hypothesis, leukocyte-free (PRGF-Endoret) and L-PRP fibrin scaffolds were prepared, and both morphogen and proinflammatory cytokine release kinetics were analyzed. Clots were incubated with culture medium to monitor protein release over 8 days. Furthermore, the different fibrin scaffolds were morphologically characterized. Results show that leukocyte-free fibrin matrices were homogenous while leukocyte-containing ones were heterogeneous, loose and cellular. Leukocyte incorporation produced a significant increase in the contents of proinflammatory cytokines interleukin (IL)-1β and IL-16 but not in the platelet-derived growth factors release (<1.5-fold). Surprisingly, the availability of vascular endothelial growth factor suffered an important decrease after 3 days of incubation in the case of L-PRP matrices. While the release of proinflammatory cyto-kines was almost absent or very low from PRGF-Endoret, the inclusion of leukocytes induced a major increase in these cytokines, which was characterized by the presence of a latent period. The PRGF-Endoret matrices were stable during the 8 days of incubation. The inclusion of leukocytes alters the growth factors release profile and also increased the dose of proinflammatory cytokines. © 2014 Wiley Periodicals, Inc.


PubMed | Foundation Eduardo Anitua
Type: Journal Article | Journal: Current pharmaceutical biotechnology | Year: 2016

The field of medicine is rapidly moving towards the development of personalized treatments and non-invasive tools to achieve a more predictable and optimal tissue regeneration. In this sense, the goal of periodontal healing is to arrest disease progression and functionally regenerate all the tissues that comprise the periodontium. The latter implies a well-orchestrated interaction among oral cells, growth factors and extracellular matrix. Although several procedures are performed in an attempt to regenerate lost periodontal tissue, outcomes are not always predictable. Growth factors represent a class of biologically active polypeptides that have a critical role in the healing process. Their use provides a new paradigm to understand the regenerative medicine. The use of platelet- rich plasma (PRP) products as a local source and delivery system of autologous growth factors has emerged recently. Among them, PRGF stands for its remarkable stimulatory effect on oral tissue regeneration, making it a very safe and successful tool with a great value in Dentistry.


PubMed | Foundation Eduardo Anitua and Institute Investigacion Hospital 12 Of Octubre I12
Type: | Journal: Journal of controlled release : official journal of the Controlled Release Society | Year: 2015

Parkinsons disease is a common neurodegenerative disorder of unknown pathogenesis characterized by the loss of nigrostriatal dopaminergic neurons. Oxidative stress, microglial activation and inflammatory responses seem to contribute to the pathogenesis. Recent data showed that growth factors mediate neuroprotection in rodent models of Parkinsons disease, modulating pro-inflammatory processes. Based on our recent studies showing that plasma rich in growth factors (PRGF-Endoret) mediates neuroprotection as inflammatory moderator in Alzheimers disease, in the present study we examined the effects of plasma rich in growth factors (PRGF-Endoret) in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mouse as a translational therapeutic approach for Parkinsons disease. We found substantial neuroprotection by PRGF-Endoret in our model of Parkinsons disease, which resulted in diminished inflammatory responses and improved motor performance. Additionally, these effects were associated with robust reduction in nuclear transcription factor-B (NF-B) activation, and nitric oxide (NO), cyclooxygenase-2 (COX-2), and tumor necrosis factor-alpha (TNF-) expression in the substantia nigra. We propose that PRGF-Endoret can prevent dopaminergic degeneration via an NF-B-dependent signaling process. As the clinical safety profile of PRGF-Endoret is already established, these data suggest that PRGF-Endoret provides a novel neuroprotective strategy for Parkinsons disease.


PubMed | Foundation Eduardo Anitua
Type: Journal Article | Journal: Current pharmaceutical biotechnology | Year: 2016

Optimal skin repair has been a desired goal for many researchers. Recently, plasma rich in growth factors (PRGF) has gained importance in dermatology proving it is beneficial effects in wound healing and cutaneous regeneration.The anti-fibrotic, pro-contractile and photo-protective effect of PRGF on dermal fibroblasts and 3D skin models has been evaluated.The effect against TGF1 induced myofibroblast differentiation was tested. Cell contractile activity over collagen gel matrices was analyzed and the effect against UV derived photo-oxidative stress was assessed. The effectiveness of PRGF obtained from young aged and middle aged donors was compared. Furthermore, 3D organotypic skin explants were used as human skin models with the aim of analyzing ex vivo cutaneous preventive and regenerative photo-protection after UV exposure.TGF1 induced myofibroblast levels decreased significantly after treatment with PRGF while the contractile activity increased compared to the control group. After UV irradiation, cell survival was promoted while apoptotic and ROS levels were noticeably reduced. Photo-exposed 3D explants showed higher levels of metabolic activity and lower levels of necrosis, cell damage, irritation and ROS formation when treated with PRGF. The histological integrity and connective tissue fibers showed lower signals of photodamage among PRGF injected skin models. No significant differences for the assessed biological outcomes were observed when PRGF obtained from young aged and middle aged donors were compared.These findings suggest that this autologous approach might be useful for antifibrotic wound healing and provide an effective protection against sun derived photo-oxidative stress regardless the age of the patient.

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