The Experts below are selected from a list of 3111 Experts worldwide ranked by ideXlab platform
Shelly E Sakiyamaelbert - One of the best experts on this subject based on the ideXlab platform.
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Fibrin based tissue engineering Scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Philip J Johnson, Stanley R Parker, Shelly E SakiyamaelbertAbstract:The purpose of this study was to evaluate the effects of Fibrin Scaffolds on subacute rat spinal cord injury (SCI). Long Evans rats were anesthetized and underwent a dorsal hemisection injury, two weeks later the injury site was re-exposed, scar tissue was removed, and a Fibrin Scaffold was implanted into the wound site. An effective method for Fibrin Scaffold implantation following subacute SCI was investigated based on the presence of Fibrin within the lesion site and morphological analysis 1 week after implantation. Pre-polymerized Fibrin Scaffolds were found to be present within the lesion site 1 week after treatment and were used for the remainder of the study. Fibrin Scaffolds were then implanted for 2 and 4 weeks, after which spinal cords were harvested and evaluated using markers for neurons, astrocytes, and chondroitin sulfate proteoglycans. Compared to untreated control, the Fibrin-treated group had significantly higher levels of neural fiber staining in the lesion site at 2 and 4 weeks after treatment, and the accumulation of glial fibrillary acidic protein (GFAP) positive reactive astrocytes surrounding the lesion was delayed. These results show that Fibrin is conducive to regeneration and cellular migration, and illustrates the advantage of using Fibrin as a Scaffold for drug delivery and cell-based therapies for SCI.
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controlled release of neurotrophin 3 from Fibrin based tissue engineering Scaffolds enhances neural fiber sprouting following subacute spinal cord injury
Biotechnology and Bioengineering, 2009Co-Authors: Philip J Johnson, Stanley R Parker, Shelly E SakiyamaelbertAbstract:This study investigated whether delayed treatment of spinal cord injury with controlled release of neurotrophin-3 (NT-3) from Fibrin Scaffolds can stimulate enhanced neural fiber sprouting. Long Evans rats received a T9 dorsal hemisection spinal cord injury. Two weeks later, the injury site was re-exposed, and either a Fibrin Scaffold alone, a Fibrin Scaffold containing a heparin-based delivery system with different concentrations of NT-3 (500 and 1000 ng/mL), or a Fibrin Scaffold containing 1000 ng/mL of NT-3 (no delivery system) was implanted into the injury site. The injured spinal cords were evaluated for morphological differences using markers for neurons, astrocytes, and chondroitin sulfate proteoglycans 2 weeks after treatment. The addition of 500 ng/mL of NT-3 with the delivery system resulted in an increase in neural fiber density compared to Fibrin alone. These results demonstrate that the controlled release of NT-3 from Fibrin Scaffolds can enhance neural fiber sprouting even when treatment is delayed 2 weeks following injury.
Gorka Orive - One of the best experts on this subject based on the ideXlab platform.
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leukocyte inclusion within a platelet rich plasma derived Fibrin Scaffold stimulates a more pro inflammatory environment and alters Fibrin properties
PLOS ONE, 2015Co-Authors: Eduardo Anitua, Sabino Padilla, Mar Zalduendo, Maria Troya, Gorka OriveAbstract: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 NFĸB 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.
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endogenous morphogens and Fibrin bioScaffolds for stem cell therapeutics
Trends in Biotechnology, 2013Co-Authors: Eduardo Anitua, Roberto Prado, Gorka OriveAbstract:Clinical translation of mesenchymal stem cells (MSCs) is leading to optimization of procedures for ex vivo expansion. Endogenous growth factors and Fibrin Scaffolds can be used to support MSC expansion and transplantation. Cell growth on a Fibrin Scaffold mimics the 3D environment of tissue and facilitates handling and subsequent transplantation. This approach is presented as an essential toolbox in the substitution of fetal bovine serum in all large-scale ex vivo processes, providing quick and safe expansion of MSCs. This paper reviews the state of the art of platelet-rich plasma technology applied to clinical use of stem cells, focusing on current technology and methods, new challenges, and controversies.
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Platelet-Rich Plasma to Improve the Bio-Functionality of Biomaterials
BioDrugs, 2013Co-Authors: Eduardo Anitua, Ricardo Tejero, Mohammad Hamdan Alkhraisat, Gorka OriveAbstract:Growth factors and cytokines are active players in controlling the different stages of wound healing and tissue regeneration. Recent trends in personalized regenerative medicine involve using patient’s own platelet-rich plasma for stimulating wound healing and tissue regeneration. This technology provides a complex cocktail of growth factors and even a Fibrin Scaffold with multiple biologic effects. In the last few years, an increasing number of studies provide evidence of the potential of combining platelet-rich plasma with different biomaterials in order to improve their properties, including handling, administration, bioactivity, and level of osseointegration, among others. In this review, we discuss the use of platelet-rich plasma as an alternative, easy, cost-effective, and controllable strategy for the release of high concentrations of many endogenous growth factors. Additionally, we provide an overview of the current progress and future directions of research combining different types of biomaterials with platelet-rich plasma in tissue engineering and regenerative medicine.
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High-throughput proteomic characterization of plasma rich in growth factors (PRGF-Endoret)-derived Fibrin clot interactome.
Journal of Tissue Engineering and Regenerative Medicine, 2013Co-Authors: Eduardo Anitua, Roberto Prado, Mikel Azkargorta, Eva Rodríguez-suárez, Ibon Iloro, Juan Casado-vela, Felix Elortza, Gorka OriveAbstract:Plasma rich in growth factors (PRGF®-Endoret®) is an autologous technology that contains a set of proteins specifically addressed to wound healing and tissue regeneration. The Scaffold formed by using this technology is a clot mainly composed of Fibrin protein, forming a three-dimensional (3D) macroscopic network. This biomaterial is easily obtained by biotechnological means from blood and can be used in a range of situations to help wound healing and tissue regeneration. Although the main constituent of this clot is the Fibrin Scaffold, little is known about other proteins interacting in this clot that may act as adjuvants in the healing process. The aim of this study was to characterize the proteins enclosed by PRGF–Endoret Scaffold, using a double-proteomic approach that combines 1D-SDS–PAGE approach followed by LC–MS/MS, and 2-DE followed by MALDI–TOF/TOF. The results presented here provide a description of the catalogue of key proteins in close contact with the Fibrin Scaffold. The obtained lists of proteins were grouped into families and networks according to gene ontology. Taken together, an enrichment of both proteins and protein families specifically involved in tissue regeneration and wound healing has been found. Copyright © 2013 John Wiley & Sons, Ltd.
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Perspectives and challenges in regenerative medicine using plasma rich in growth factors
Journal of Controlled Release: Official Journal of the Controlled Release Society, 2011Co-Authors: Eduardo Anitua, Mohammad Hamdan Alkhraisat, Gorka OriveAbstract:Plasma rich in growth factors (PRGF-Endoret) is an endogenous therapeutic technology that is gaining interest in regenerative medicine due to its potential to stimulate and accelerate tissue healing and bone regeneration. This autologous biotechnology is designed for the in situ delivery of multiple cellular modulators and the formation of a Fibrin Scaffold, thereby providing different formulations that can be widely used in numerous medical and scientific fields including dentistry, oral implantology, orthopedics, ulcer treatment and tissue engineering among others. Here we discuss the important progress that has been accomplished in this field. Furthermore, a comprehensive outlook of the intriguing therapeutic applications of this technology is presented.
Paulo Jose Ferreira Tucci - One of the best experts on this subject based on the ideXlab platform.
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cell therapy attenuates cardiac dysfunction post myocardial infarction effect of timing routes of injection and a Fibrin Scaffold
PLOS ONE, 2009Co-Authors: Juliana Sanajotti Nakamuta, Maria E. Danoviz, Giovana A. Gonçalves, Paula F. Vassallo, Isomar T. Schettert, Claudia Becker, Fabio Marques, Leonardo Hunaldo Dos Santos, Paulo Jose Ferreira TucciAbstract:Background Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer Scaffold to improve cardiac cell retention and function. Methodology/Principal Findings 99mTc-labeled BMC (6×106 cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV+) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by γ-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%). Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16%) vs. 1, 2 or 3 (average of 7%) days post-MI. Cardiac cell retention was further improved by an injectable Fibrin Scaffold at day 3 post-MI (17 vs. 7%), even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. Conclusions/Significance These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a Fibrin Scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these novel approaches.
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Cell therapy attenuates cardiac dysfunction post myocardial infarction: Effect of timing, routes of injection and a Fibrin Scaffold
PLoS ONE, 2009Co-Authors: Juliana Sanajotti Nakamuta, Maria E. Danoviz, Fabio L.n. Marques, Leonardo Dos Santos, Giovana A. Gonçalves, Paula F. Vassallo, Isomar T. Schettert, Claudia Becker, Paulo Jose Ferreira Tucci, Jose E. KriegerAbstract:BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer Scaffold to improve cardiac cell retention and function.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: (99m)Tc-labeled BMC (6 x 10(6) cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV(+)) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by gamma-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (
Philip J Johnson - One of the best experts on this subject based on the ideXlab platform.
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Tissue-engineered Fibrin Scaffolds containing neural progenitors enhance functional recovery in a subacute model of SCI.
Soft Matter, 2010Co-Authors: Philip J Johnson, Alexander M. Tatara, Dylan A. Mccreedy, Alicia Shiu, Shelly E. Sakiyama-elbertAbstract:Two recurring problems with stem/neural progenitor cell (NPC) transplantation therapies for spinal cord injury (SCI) are poor cell survival and uncontrolled cell differentiation. The current study evaluated the viability and differentiation of embryonic stem cell-derived neural progenitor cells (ESNPCs) transplanted within Fibrin Scaffolds containing growth factors (GFs) and a heparin-binding delivery system (HBDS) to enhance cell survival and direct differentiation into neurons. Mouse ESNPCs were generated from mouse embryonic stem cells (ESCs) using a 4−/4+ retinoic acid (RA) induction protocol that resulted in a population of cells that was 70% nestin positive NPCs. The ESNPCs were transplanted directly into a rat subacute dorsal hemisection lesion SCI model. ESNPCs were either encapsulated in a Fibrin Scaffold; encapsulated in Fibrin containing the HBDS, neurotrophin-3 (NT-3) and platelet derived growth factor (PDGF-AA); or encapsulated in Fibrin Scaffolds with NT-3 and PDGF-AA without the HBDS. We report that the combination of GFs and Fibrin Scaffold (without HBDS) enhanced the total number of ESNPCs present in the treated spinal cords and increased the number of ESNPC-derived NeuN positive neurons 8 weeks after transplantation. All experimental groups treated with ESNPCs exhibited an increase in behavioral function 4 weeks after transplantation. In a subset of animals, the ESNPCs over-proliferated as evidenced by SSEA-1 positive/Ki67 positive ESCs found at 4 and 8 weeks. These results demonstrate the potential of tissue-engineered Fibrin Scaffolds to enhance the survival of NPCs and highlight the need to purify cell populations used in therapies for SCI.
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Fibrin based tissue engineering Scaffolds enhance neural fiber sprouting and delay the accumulation of reactive astrocytes at the lesion in a subacute model of spinal cord injury
Journal of Biomedical Materials Research Part A, 2010Co-Authors: Philip J Johnson, Stanley R Parker, Shelly E SakiyamaelbertAbstract:The purpose of this study was to evaluate the effects of Fibrin Scaffolds on subacute rat spinal cord injury (SCI). Long Evans rats were anesthetized and underwent a dorsal hemisection injury, two weeks later the injury site was re-exposed, scar tissue was removed, and a Fibrin Scaffold was implanted into the wound site. An effective method for Fibrin Scaffold implantation following subacute SCI was investigated based on the presence of Fibrin within the lesion site and morphological analysis 1 week after implantation. Pre-polymerized Fibrin Scaffolds were found to be present within the lesion site 1 week after treatment and were used for the remainder of the study. Fibrin Scaffolds were then implanted for 2 and 4 weeks, after which spinal cords were harvested and evaluated using markers for neurons, astrocytes, and chondroitin sulfate proteoglycans. Compared to untreated control, the Fibrin-treated group had significantly higher levels of neural fiber staining in the lesion site at 2 and 4 weeks after treatment, and the accumulation of glial fibrillary acidic protein (GFAP) positive reactive astrocytes surrounding the lesion was delayed. These results show that Fibrin is conducive to regeneration and cellular migration, and illustrates the advantage of using Fibrin as a Scaffold for drug delivery and cell-based therapies for SCI.
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Controlled Release of Neurotrophin-3 and Platelet-Derived Growth Factor from Fibrin Scaffolds Containing Neural Progenitor Cells Enhances Survival and Differentiation into Neurons in a Subacute Model of SCI:
Cell Transplantation, 2010Co-Authors: Philip J Johnson, Alexander M. Tatara, Alicia Shiu, Shelly E. Sakiyama-elbertAbstract:A consistent problem with stem/neural progenitor cell transplantation following spinal cord injury (SCI) is poor cell survival and uncontrolled differentiation following transplantation. The current study evaluated the feasibility of enhancing embryonic stem cell-derived neural progenitor cell (ESNPC) viability and directing their differentiation into neurons and oligodendrocytes by embedding the ESNPCs in Fibrin Scaffolds containing growth factors (GF) and a heparin-binding delivery system (HBDS) in a subacute rat model of SCI. Mouse ESNPCs were generated from mouse embryonic stem cells (ESCs) using a 4-/4+ retinoic acid (RA) induction protocol. The ESNPCs were then transplanted as embryoid bodies (EBs, 70% neural progenitor cells) into the subacute model of SCI. ESNPCs (10 EBs per animal) were implanted directly into the SCI lesion, encapsulated in Fibrin Scaffolds, encapsulated in Fibrin Scaffolds containing the HBDS, neurotrophin-3 (NT-3), and platelet-derived growth factor (PDGF), or encapsulated in Fibrin Scaffolds with NT-3 and PDGF with no HBDS. We report here that the combination of the NT-3, PDGF, and Fibrin Scaffold (with or without HBDS) enhanced the total number of ESNPCs present in the spinal cord lesion 2 weeks after injury. In addition, the inclusion of the HBDS with growth factor resulted in an increase in the number of ESNPC-derived NeuN-positive neurons. These results demonstrate the ability of Fibrin Scaffolds and the controlled release of growth factors to enhance the survival and differentiation of neural progenitor cells following transplantation into a SCI model.
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controlled release of neurotrophin 3 from Fibrin based tissue engineering Scaffolds enhances neural fiber sprouting following subacute spinal cord injury
Biotechnology and Bioengineering, 2009Co-Authors: Philip J Johnson, Stanley R Parker, Shelly E SakiyamaelbertAbstract:This study investigated whether delayed treatment of spinal cord injury with controlled release of neurotrophin-3 (NT-3) from Fibrin Scaffolds can stimulate enhanced neural fiber sprouting. Long Evans rats received a T9 dorsal hemisection spinal cord injury. Two weeks later, the injury site was re-exposed, and either a Fibrin Scaffold alone, a Fibrin Scaffold containing a heparin-based delivery system with different concentrations of NT-3 (500 and 1000 ng/mL), or a Fibrin Scaffold containing 1000 ng/mL of NT-3 (no delivery system) was implanted into the injury site. The injured spinal cords were evaluated for morphological differences using markers for neurons, astrocytes, and chondroitin sulfate proteoglycans 2 weeks after treatment. The addition of 500 ng/mL of NT-3 with the delivery system resulted in an increase in neural fiber density compared to Fibrin alone. These results demonstrate that the controlled release of NT-3 from Fibrin Scaffolds can enhance neural fiber sprouting even when treatment is delayed 2 weeks following injury.
Juliana Sanajotti Nakamuta - One of the best experts on this subject based on the ideXlab platform.
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cell therapy attenuates cardiac dysfunction post myocardial infarction effect of timing routes of injection and a Fibrin Scaffold
PLOS ONE, 2009Co-Authors: Juliana Sanajotti Nakamuta, Maria E. Danoviz, Giovana A. Gonçalves, Paula F. Vassallo, Isomar T. Schettert, Claudia Becker, Fabio Marques, Leonardo Hunaldo Dos Santos, Paulo Jose Ferreira TucciAbstract:Background Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer Scaffold to improve cardiac cell retention and function. Methodology/Principal Findings 99mTc-labeled BMC (6×106 cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV+) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by γ-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%). Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16%) vs. 1, 2 or 3 (average of 7%) days post-MI. Cardiac cell retention was further improved by an injectable Fibrin Scaffold at day 3 post-MI (17 vs. 7%), even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. Conclusions/Significance These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a Fibrin Scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these novel approaches.
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Cell therapy attenuates cardiac dysfunction post myocardial infarction: Effect of timing, routes of injection and a Fibrin Scaffold
PLoS ONE, 2009Co-Authors: Juliana Sanajotti Nakamuta, Maria E. Danoviz, Fabio L.n. Marques, Leonardo Dos Santos, Giovana A. Gonçalves, Paula F. Vassallo, Isomar T. Schettert, Claudia Becker, Paulo Jose Ferreira Tucci, Jose E. KriegerAbstract:BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer Scaffold to improve cardiac cell retention and function.\n\nMETHODOLOGY/PRINCIPAL FINDINGS: (99m)Tc-labeled BMC (6 x 10(6) cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV(+)) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by gamma-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (