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Article ; Online: Neurite Outgrowth and Gene Expression Profile Correlate with Efficacy of Human Induced Pluripotent Stem Cell-Derived Dopamine Neuron Grafts.

Hills, Rachel / Mossman, Jim A / Bratt-Leal, Andres M / Tran, Ha / Williams, Roy M / Stouffer, David G / Sokolova, Irina V / Sanna, Pietro P / Loring, Jeanne F / Lelos, Mariah J

Stem cells and development

2023 Volume 32, Issue 13-14, Page(s) 387–397

Abstract: Transplantation of human induced pluripotent stem cell-derived dopaminergic (iPSC-DA) neurons is a promising therapeutic strategy for Parkinson's disease (PD). To assess optimal cell characteristics and reproducibility, we evaluated the efficacy of iPSC- ... ...

Abstract	Transplantation of human induced pluripotent stem cell-derived dopaminergic (iPSC-DA) neurons is a promising therapeutic strategy for Parkinson's disease (PD). To assess optimal cell characteristics and reproducibility, we evaluated the efficacy of iPSC-DA neuron precursors from two individuals with sporadic PD by transplantation into a hemiparkinsonian rat model after differentiation for either 18 (d18) or 25 days (d25). We found similar graft size and dopamine (DA) neuron content in both groups, but only the d18 cells resulted in recovery of motor impairments. In contrast, we report that d25 grafts survived equally as well and produced grafts rich in tyrosine hydroxylase-positive neurons, but were incapable of alleviating any motor deficits. We identified the mechanism of action as the extent of neurite outgrowth into the host brain, with d18 grafts supporting significantly more neurite outgrowth than nonfunctional d25 grafts. RNAseq analysis of the cell preparation suggests that graft efficacy may be enhanced by repression of differentiation-associated genes by REST, defining the optimal predifferentiation state for transplantation. This study demonstrates for the first time that DA neuron grafts can survive well in vivo while completely lacking the capacity to induce recovery from motor dysfunction. In contrast to other recent studies, we demonstrate that neurite outgrowth is the key factor determining graft efficacy and our gene expression profiling revealed characteristics of the cells that may predict their efficacy. These data have implication for the generation of DA neuron grafts for clinical application.
MeSH term(s)	Humans ; Rats ; Animals ; Dopaminergic Neurons ; Induced Pluripotent Stem Cells ; Transcriptome ; Reproducibility of Results ; Cell Differentiation/physiology ; Neuronal Outgrowth
Language	English
Publishing date	2023-06-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2142214-X
ISSN	1557-8534 ; 1547-3287
ISSN (online)	1557-8534
ISSN	1547-3287
DOI	10.1089/scd.2023.0043
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Article ; Online: A microparticle approach to morphogen delivery within pluripotent stem cell aggregates.

Bratt-Leal, Andrés M / Nguyen, Anh H / Hammersmith, Katy A / Singh, Ankur / McDevitt, Todd C

Biomaterials

2013 Volume 34, Issue 30, Page(s) 7227–7235

Abstract: Stem cell fate and specification is largely controlled by extrinsic cues that comprise the 3D microenvironment. Biomaterials can serve to control the spatial and temporal presentation of morphogenic molecules in order to direct stem cell fate decisions. ... ...

Abstract	Stem cell fate and specification is largely controlled by extrinsic cues that comprise the 3D microenvironment. Biomaterials can serve to control the spatial and temporal presentation of morphogenic molecules in order to direct stem cell fate decisions. Here we describe a microparticle (MP)-based approach to deliver growth factors within multicellular aggregates to direct pluripotent stem cell differentiation. Compared to conventional soluble delivery methods, gelatin MPs laden with BMP4 or noggin induced efficient gene expression of mesoderm and ectoderm lineages, respectively, despite using nearly 12-fold less total growth factor. BMP4-laden MPs increased the percentage of cells expressing GFP under the control of the Brachyury-T promoter as visualized by whole-mount confocal imaging and quantified by flow cytometry. Furthermore, the ability to localize MPs laden with different morphogens within a particular hemisphere of stem cell aggregates allowed for spatial control of differentiation within 3D cultures. Overall, localized delivery of growth factors within multicellular aggregates from microparticle delivery vehicles is an important step towards scalable differentiation technologies and the study of morphogen gradients in pluripotent stem cell differentiation.
MeSH term(s)	Animals ; Bone Morphogenetic Protein 4/pharmacology ; Cell Aggregation/drug effects ; Cell Differentiation/drug effects ; Coculture Techniques ; Embryoid Bodies/cytology ; Embryoid Bodies/drug effects ; Embryoid Bodies/metabolism ; Gelatin/pharmacology ; Mesoderm/cytology ; Mesoderm/drug effects ; Mice ; Microspheres ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/drug effects ; Pluripotent Stem Cells/metabolism ; Spheroids, Cellular/cytology ; Spheroids, Cellular/drug effects ; Spheroids, Cellular/metabolism
Chemical Substances	Bone Morphogenetic Protein 4 ; Gelatin (9000-70-8)
Language	English
Publishing date	2013-07-01
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2013.05.079
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Article ; Online: Engineering the embryoid body microenvironment to direct embryonic stem cell differentiation.

Bratt-Leal, Andrés M / Carpenedo, Richard L / McDevitt, Todd C

Biotechnology progress

2009 Volume 25, Issue 1, Page(s) 43–51

Abstract: Embryonic stem cells (ESCs) are pluripotent cells capable of differentiating into all somatic and germ cell types. The intrinsic ability of pluripotent cells to generate a vast array of different cells makes ESCs a robust resource for a variety of cell ... ...

Abstract	Embryonic stem cells (ESCs) are pluripotent cells capable of differentiating into all somatic and germ cell types. The intrinsic ability of pluripotent cells to generate a vast array of different cells makes ESCs a robust resource for a variety of cell transplantation and tissue engineering applications, however, efficient and controlled means of directing ESC differentiation is essential for the development of regenerative therapies. ESCs are commonly differentiated in vitro by spontaneously self-assembling in suspension culture into 3D cell aggregates called embryoid bodies (EBs), which mimic many of the hallmarks of early embryonic development, yet the 3D organization and structure of EBs also presents unique challenges to effectively direct the differentiation of the cells. ESC differentiation is strongly influenced by physical and chemical signals comprising the local extracellular microenvironment, thus current methods to engineer EB differentiation have focused primarily on spatially controlling EB size, adding soluble factors to the media, or culturing EBs on or within natural or synthetic extracellular matrices. Although most such strategies aim to influence differentiation from the exterior of EBs, engineering the microenvironment directly within EBs enables new opportunities to efficiently direct the fate of the cells by locally controlling the presentation of morphogenic cues.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Humans ; Tissue Engineering/methods
Language	English
Publishing date	2009-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Review
ZDB-ID	165657-0
ISSN	1520-6033 ; 8756-7938
ISSN (online)	1520-6033
ISSN	8756-7938
DOI	10.1002/btpr.139
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Article: A microparticle approach to morphogen delivery within pluripotent stem cell aggregates

Bratt-Leal, Andrés M / Nguyen, Anh H / Hammersmith, Katy A / Singh, Ankur / McDevitt, Todd C

Biomaterials. 2013 Oct., v. 34, no. 30

2013

Abstract	Stem cell fate and specification is largely controlled by extrinsic cues that comprise the 3D microenvironment. Biomaterials can serve to control the spatial and temporal presentation of morphogenic molecules in order to direct stem cell fate decisions. Here we describe a microparticle (MP)-based approach to deliver growth factors within multicellular aggregates to direct pluripotent stem cell differentiation. Compared to conventional soluble delivery methods, gelatin MPs laden with BMP4 or noggin induced efficient gene expression of mesoderm and ectoderm lineages, respectively, despite using nearly 12-fold less total growth factor. BMP4-laden MPs increased the percentage of cells expressing GFP under the control of the Brachyury-T promoter as visualized by whole-mount confocal imaging and quantified by flow cytometry. Furthermore, the ability to localize MPs laden with different morphogens within a particular hemisphere of stem cell aggregates allowed for spatial control of differentiation within 3D cultures. Overall, localized delivery of growth factors within multicellular aggregates from microparticle delivery vehicles is an important step towards scalable differentiation technologies and the study of morphogen gradients in pluripotent stem cell differentiation.
Keywords	biocompatible materials ; cell aggregates ; cell differentiation ; flow cytometry ; gelatin ; gene expression ; growth factors ; image analysis ; stem cells
Language	English
Dates of publication	2013-10
Size	p. 7227-7235.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2013.05.079
Database	NAL-Catalogue (AGRICOLA)

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Article: Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates

Bratt-Leal, Andrés M / Kepple, Kirsten L / Carpenedo, Richard L / Cooke, Marissa T / McDevitt, Todd C

Integrative biology. 2011 Dec. 1, v. 3, no. 12

2011

Abstract: The controlled assembly and organization of multi-cellular systems to mimic complex tissue structures is critical to the engineering of tissues for therapeutic and diagnostic applications. Recent advances in micro-scale technologies to control multi- ... ...

Abstract	The controlled assembly and organization of multi-cellular systems to mimic complex tissue structures is critical to the engineering of tissues for therapeutic and diagnostic applications. Recent advances in micro-scale technologies to control multi-cellular aggregate formation typically require chemical modification of the interface between cells and materials and lack multi-scale flexibility. Here we demonstrate that simple physical entrapment of magnetic microparticles within the extracellular space of stem cells spheroids during initial formation enables scaffold-free immobilization, translocation and directed assembly of multi-cellular aggregates across multiple length and time scales, even under dynamic suspension culture conditions. The response of aggregates to externally applied magnetic fields was a direct function of microparticle incorporation, allowing for rapid and transient control of the extracellular environment as well as separation of heterogeneous populations. In addition, spatial patterning of heterogeneous spheroid populations as well as individual multi-cellular aggregates was readily achieved by imposing temporary magnetic fields. Overall, this approach provides novel routes to examine stem cell differentiation and tissue morphogenesis with applications that encompass the creation of new model systems for developmental biology, scaffold-free tissue engineering strategies and scalable bioprocessing technologies.
Keywords	bioprocessing ; cell aggregates ; cell differentiation ; extracellular space ; magnetic fields ; microparticles ; models ; morphogenesis ; stem cells ; therapeutics ; tissue engineering ; tissues
Language	English
Dates of publication	2011-1201
Size	p. 1224-1232.
Publishing place	The Royal Society of Chemistry
Document type	Article
ZDB-ID	2480063-6
ISSN	1757-9708 ; 1757-9694
ISSN (online)	1757-9708
ISSN	1757-9694
DOI	10.1039/c1ib00064k
Database	NAL-Catalogue (AGRICOLA)

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Article: Incorporation of biomaterials in multicellular aggregates modulates pluripotent stem cell differentiation

Bratt-Leal, Andrés M / Carpenedo, Richard L / Ungrin, Mark D / Zandstra, Peter W / McDevitt, Todd C

Biomaterials. 2011 Jan., v. 32, no. 1

2011

Abstract: Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell–biomaterial ... ...

Abstract	Biomaterials are increasingly being used to engineer the biochemical and biophysical properties of the extracellular stem cell microenvironment in order to tailor niche characteristics and direct cell phenotype. To date, stem cell–biomaterial interactions have largely been studied by introducing stem cells into artificial environments, such as 2D cell culture on biomaterial surfaces, encapsulation of cell suspensions within hydrogel materials, or cell seeding on 3D polymeric scaffolds. In this study, microparticles fabricated from different materials, such as agarose, PLGA and gelatin, were stably integrated, in a dose-dependent manner, within aggregates of pluripotent stem cells (PSCs) prior to differentiation as a means to directly examine stem cell–biomaterial interactions in 3D. Interestingly, the presence of the materials within the stem cell aggregates differentially modulated the gene and protein expression patterns of several differentiation markers without adversely affecting cell viability. Microparticle incorporation within 3D stem cell aggregates can control the spatial presentation of extracellular environmental cues (i.e. soluble factors, extracellular matrix and intercellular adhesion molecules) as a means to direct the differentiation of stem cells for tissue engineering and regenerative medicine applications. In addition, these results suggest that the physical presence of microparticles within stem cell aggregates does not compromise PSC differentiation, but in fact the choice of biomaterials can impact the propensity of stem cells to adopt particular differentiated cell phenotypes.
Keywords	adhesion ; agarose ; biocompatible materials ; cell aggregates ; cell differentiation ; cell suspension culture ; cell viability ; cellular microenvironment ; encapsulation ; extracellular matrix ; gelatin ; gene expression ; genes ; hydrocolloids ; medicine ; phenotype ; protein synthesis ; stem cells ; tissue engineering ; tissue repair
Language	English
Dates of publication	2011-01
Size	p. 48-56.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2010.08.113
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Microfluidic-based patterning of embryonic stem cells for in vitro development studies.

Suri, Shalu / Singh, Ankur / Nguyen, Anh H / Bratt-Leal, Andres M / McDevitt, Todd C / Lu, Hang

Lab on a chip

2013 Volume 13, Issue 23, Page(s) 4617–4624

Abstract: In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study ... ...

Abstract	In vitro recapitulation of mammalian embryogenesis and examination of the emerging behaviours of embryonic structures require both the means to engineer complexity and accurately assess phenotypes of multicellular aggregates. Current approaches to study multicellular populations in 3D configurations are limited by the inability to create complex (i.e. spatially heterogeneous) environments in a reproducible manner with high fidelity thus impeding the ability to engineer microenvironments and combinations of cells with similar complexity to that found during morphogenic processes such as development, remodelling and wound healing. Here, we develop a multicellular embryoid body (EB) fusion technique as a higher-throughput in vitro tool, compared to a manual assembly, to generate developmentally relevant embryonic patterns. We describe the physical principles of the EB fusion microfluidic device design; we demonstrate that >60 conjoined EBs can be generated overnight and emulate a development process analogous to mouse gastrulation during early embryogenesis. Using temporal delivery of bone morphogenic protein 4 (BMP4) to embryoid bodies, we recapitulate embryonic day 6.5 (E6.5) during mouse embryo development with induced mesoderm differentiation in murine embryonic stem cells leading to expression of Brachyury-T-green fluorescent protein (T-GFP), an indicator of primitive streak development and mesoderm differentiation during gastrulation. The proposed microfluidic approach could be used to manipulate hundreds or more of individual embryonic cell aggregates in a rapid fashion, thereby allowing controlled differentiation patterns in fused multicellular assemblies to generate complex yet spatially controlled microenvironments.
MeSH term(s)	Animals ; Bone Morphogenetic Protein 4/genetics ; Bone Morphogenetic Protein 4/metabolism ; Cell Differentiation ; Cells, Cultured ; Embryoid Bodies/cytology ; Embryoid Bodies/metabolism ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/metabolism ; Fetal Proteins/genetics ; Fetal Proteins/metabolism ; Green Fluorescent Proteins/genetics ; Green Fluorescent Proteins/metabolism ; Mesoderm/cytology ; Mice ; Microfluidic Analytical Techniques/instrumentation ; Recombinant Fusion Proteins/biosynthesis ; Recombinant Fusion Proteins/genetics ; T-Box Domain Proteins/genetics ; T-Box Domain Proteins/metabolism ; Transfection
Chemical Substances	Bone Morphogenetic Protein 4 ; Fetal Proteins ; Recombinant Fusion Proteins ; T-Box Domain Proteins ; Green Fluorescent Proteins (147336-22-9) ; Brachyury protein (EQ43SC3GDB)
Language	English
Publishing date	2013-10-08
Publishing country	England
Document type	Journal Article ; Research Support, American Recovery and Reinvestment Act ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2056646-3
ISSN	1473-0189 ; 1473-0197
ISSN (online)	1473-0189
ISSN	1473-0197
DOI	10.1039/c3lc50663k
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Article ; Online: Magnetic manipulation and spatial patterning of multi-cellular stem cell aggregates.

Bratt-Leal, Andrés M / Kepple, Kirsten L / Carpenedo, Richard L / Cooke, Marissa T / McDevitt, Todd C

Integrative biology : quantitative biosciences from nano to macro

2011 Volume 3, Issue 12, Page(s) 1224–1232

Abstract	The controlled assembly and organization of multi-cellular systems to mimic complex tissue structures is critical to the engineering of tissues for therapeutic and diagnostic applications. Recent advances in micro-scale technologies to control multi-cellular aggregate formation typically require chemical modification of the interface between cells and materials and lack multi-scale flexibility. Here we demonstrate that simple physical entrapment of magnetic microparticles within the extracellular space of stem cells spheroids during initial formation enables scaffold-free immobilization, translocation and directed assembly of multi-cellular aggregates across multiple length and time scales, even under dynamic suspension culture conditions. The response of aggregates to externally applied magnetic fields was a direct function of microparticle incorporation, allowing for rapid and transient control of the extracellular environment as well as separation of heterogeneous populations. In addition, spatial patterning of heterogeneous spheroid populations as well as individual multi-cellular aggregates was readily achieved by imposing temporary magnetic fields. Overall, this approach provides novel routes to examine stem cell differentiation and tissue morphogenesis with applications that encompass the creation of new model systems for developmental biology, scaffold-free tissue engineering strategies and scalable bioprocessing technologies.
MeSH term(s)	Animals ; Cell Aggregation/physiology ; Cell Aggregation/radiation effects ; Cell Separation/methods ; Cells, Cultured ; Embryonic Stem Cells/cytology ; Embryonic Stem Cells/physiology ; Embryonic Stem Cells/radiation effects ; Magnetic Fields ; Mice ; Micromanipulation/methods ; Spheroids, Cellular/cytology ; Spheroids, Cellular/physiology ; Spheroids, Cellular/radiation effects
Language	English
Publishing date	2011-11-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2480063-6
ISSN	1757-9708 ; 1757-9694
ISSN (online)	1757-9708
ISSN	1757-9694
DOI	10.1039/c1ib00064k
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Systematic engineering of 3D pluripotent stem cell niches to guide blood development.

Purpura, Kelly A / Bratt-Leal, Andrés M / Hammersmith, Katy A / McDevitt, Todd C / Zandstra, Peter W

Biomaterials

2011 Volume 33, Issue 5, Page(s) 1271–1280

Abstract: Pluripotent stem cells (PSC) provide insight into development and may underpin new cell therapies, yet controlling PSC differentiation to generate functional cells remains a significant challenge. In this study we explored the concept that mimicking the ... ...

Abstract	Pluripotent stem cells (PSC) provide insight into development and may underpin new cell therapies, yet controlling PSC differentiation to generate functional cells remains a significant challenge. In this study we explored the concept that mimicking the local in vivo microenvironment during mesoderm specification could promote the emergence of hematopoietic progenitor cells from embryonic stem cells (ESCs). First, we assessed the expression of early phenotypic markers of mesoderm differentiation (E-cadherin, brachyury (T-GFP), PDGFRα, and Flk1: +/-ETPF) to reveal that E-T+P+F+ cells have the highest capacity for hematopoiesis. Second, we determined how initial aggregate size influences the emergence of mesodermal phenotypes (E-T+P+F+, E-T-P+/-F+, and E-T-P+F-) and discovered that colony forming cell (CFC) output was maximal with ~100 cells per PSC aggregate. Finally, we introduced these 100-cell PSC aggregates into a low oxygen environment (5%; to upregulate endogenous VEGF secretion) and delivered two potent blood-inductive molecules, BMP4 and TPO (bone morphogenetic protein-4 and thrombopoietin), locally from microparticles to obtain a more robust differentiation response than soluble delivery methods alone. Approximately 1.7-fold more CFCs were generated with localized delivery in comparison to exogenous delivery, while combined growth factor use was reduced ~14.2-fold. By systematically engineering the complex and dynamic environmental signals associated with the in vivo blood developmental niche we demonstrate a significant role for inductive endogenous signaling and introduce a tunable platform for enhancing PSC differentiation efficiency to specific lineages.
MeSH term(s)	Biomedical Engineering/methods ; Body Patterning/drug effects ; Bone Morphogenetic Protein 4/pharmacology ; Cell Aggregation/drug effects ; Cell-Derived Microparticles/drug effects ; Cell-Derived Microparticles/metabolism ; Gelatin/pharmacology ; Hematopoietic Stem Cells/cytology ; Humans ; Mesoderm/drug effects ; Mesoderm/embryology ; Mesoderm/metabolism ; Oxygen/pharmacology ; Phenotype ; Pluripotent Stem Cells/cytology ; Stem Cell Niche/drug effects
Chemical Substances	Bone Morphogenetic Protein 4 ; Gelatin (9000-70-8) ; Oxygen (S88TT14065)
Language	English
Publishing date	2011-11-12
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603079-8
ISSN	1878-5905 ; 0142-9612
ISSN (online)	1878-5905
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2011.10.051
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Article: Spatial distribution and acute anti-inflammatory effects of Methylprednisolone after sustained local delivery to the contused spinal cord.

Chvatal, Stacie A / Kim, Young-Tae / Bratt-Leal, Andres M / Lee, Hyunjung / Bellamkonda, Ravi V

Biomaterials

2008 Volume 29, Issue 12, Page(s) 1967–1975

Abstract: Methylprednisolone (MP) has been shown to reduce acute inflammation resulting from a secondary damage cascade initiated by the primary physical injury to the spinal cord. The current clinical practice for delivering systemic MP is inefficient, and high ... ...

Abstract	Methylprednisolone (MP) has been shown to reduce acute inflammation resulting from a secondary damage cascade initiated by the primary physical injury to the spinal cord. The current clinical practice for delivering systemic MP is inefficient, and high doses are required, resulting in adverse, undesired, dose-related side effects in patients. Here, we report a novel, minimally invasive, localized drug delivery system for delivering MP to the contused adult rat spinal cord that potentially side-steps the deleterious consequences of systemic cortico-steroid therapy. MP was encapsulated in biodegradable PLGA based nanoparticles (NP), and these nanoparticles were embedded in an agarose hydrogel for localization to the site of contusion injury. To visualize and quantify its spatial distribution within the injured spinal cord, MP was conjugated to Texas-red cadaverine prior to encapsulation in nanoparticles. When delivered via the hydrogel-nanoparticle system, MP entered the injured spinal cord and diffused up to 1.5mm deep and up to 3mm laterally into the injured spinal cord within 2 days. Furthermore, topically delivered MP significantly decreased early inflammation inside the contusion injured spinal cord as evidenced by a significant reduction in the number of ED-1(+) macrophages/activated microglia. This decreased early inflammation was accompanied by a significantly diminished expression of pro-inflammatory proteins including Calpain and iNOS. Additionally, topically delivered MP significantly reduced lesion volume 7 days after contusion injury. The minimally invasive MP delivery system reported in this study has the potential to enhance the effectiveness of MP therapy after contusion injury to the spinal cord and avoid the side effects arising from high dose cortico-steroid therapy.
MeSH term(s)	Acute Disease ; Animals ; Anti-Inflammatory Agents/administration & dosage ; Delayed-Action Preparations/administration & dosage ; Drug Carriers/administration & dosage ; Drug Carriers/chemistry ; Male ; Methylprednisolone/administration & dosage ; Methylprednisolone/pharmacokinetics ; Rats ; Rats, Sprague-Dawley ; Sepharose/chemistry ; Spinal Cord Injuries/drug therapy ; Spinal Cord Injuries/metabolism ; Spinal Cord Injuries/pathology ; Tissue Distribution ; Treatment Outcome
Chemical Substances	Anti-Inflammatory Agents ; Delayed-Action Preparations ; Drug Carriers ; Sepharose (9012-36-6) ; Methylprednisolone (X4W7ZR7023)
Language	English
Publishing date	2008-02-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	603079-8
ISSN	0142-9612
ISSN	0142-9612
DOI	10.1016/j.biomaterials.2008.01.002
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