TISSUE ENGINEERING FOR PEDIATRIC APPLICATIONS
Jane Kathryn
Rice Universitycity: Houston country: United States (us)
Grant 1R13HD071726-01 from Eunice Kennedy Shriver National Institute Of Child Health & Human Development
Abstract: This Conference Grant application will support a Pre-Conference Workshop on "Tissue Engineering for Pediatric Applications," to be held on December 11, 2011, in advance of the Annual Meeting of Tissue Engineering and Regenerative Medicine International Society - North America (TERMIS-NA) in Houston, TX. The target audience is biomedical scientists, bioengineers, and clinicians. Many investigators in the field of tissue engineering cite congenital defects and other needs for regenerative medicine in children (among other reasons) as compelling justification for their research. However, pediatric applications actually represent a surprisingly small fraction of research presented and published in the tissue engineering field. The mission of this workshop is (i) to draw attention to the specific tissue engineering and regenerative medicine needs of prenatal, neonatal, and pediatric patients; (ii) to clarify how needs for pediatric patients differ from the needs of adult patients; (iii) to inform clinicians (pediatric or otherwise) about this research, especially those who might not otherwise attend the TERMIS-NA conference; (iv) to enhance collaboration and initiate discussions between pediatric clinicians and tissue engineering researchers; and (v) to provide a platform to highlight the research of young investigators in the field of pediatric tissue engineering and regenerative medicine. To accomplish this mission, we will feature a full day of keynote lectures and oral presentations describing research investigations on pediatric tissue engineering applications including but not limited to cardiovascular, orthopedic, craniofacial, gastrointestinal, and urological. We will feature a program of invited speakers at various academic ranks from clinical and basic research institutions. All of the speakers are involved in pediatric clinical practice and/or research involving tissue engineering for pediatric applications. Clinicians, biomedical scientists, and bioengineers will be able to interact and discuss future directions through panels held after the technical presentations and numerous opportunities for informal engagement. There will also be a section of the poster session of the main TERMIS-NA conference dedicated to pediatric applications, and awards for best trainee posters will be given. Women and minorities are represented in the list of invited speakers and serve on the conference organizing committee. In addition, we will encourage trainees and faculty who are women, under-represented minorities, or persons with disabilities to attend the workshop and apply for registration discounts. A significant portion of the attendees will be persons also attending the annual TERMIS-NA conference, although we will also target a broader audience (locally and nationally). To promote attendance by clinicians, we will hold the workshop on the weekend. Publicity about the workshop will include information about child care resources. The Houston locale, and the involvement of Texas Children´s Hospital as the primary institutional sponsor, will provide a very strong scientific environment for the proposed workshop and facilitate evaluation of the depth, current status, and future challenges in pediatric tissue engineering. New technologies with the ability to engineer implantable living tissues or encourage the regeneration of tissues and organs hold great promise for the treatment and cure of a variety of birth defects and other childhood afflictions. However, a surprisingly small fraction of tissue engineering research focuses on the needs of pediatric patients when compared to adult therapies. This proposed workshop aims to bring together engineers, scientists and clinicians involved in tissue engineering research and in treating pediatric patients with tissue engineering needs in order to motivate research in these areas and enhance collaboration
Keywords: Adult; Americas; Applications Grants; Area; Attention; Award; Basic Science; Biomedical Engineering; biomedical scientist; Budgets; Cardiovascular system; Child; Child Care; Childhood; clinical practice; Clinical Research; Collaborations; Congenital Abnormality; Contracts; craniofacial; Disabled Persons; discount; Educational workshop; Engineering; Environment; Evaluation; Event; Faculty; Feedback; Future; gastrointestinal; Institution; International; Investigation; lectures; Life; Locales; Location; Logistics; meetings; member; Minority; Mission; Neonatal; new technology; North America; Oral; Organ; Orthopedics; Patients; Pediatric Hospitals; Persons; posters; prenatal; programs; Publishing; Regenerative Medicine; Research; Research Personnel; Resources; Scientist; Societies; Surveys; symposium; Technology; Texas; Tissue Engineering; tissue regeneration; Tissues; Travel; Underrepresented Minority; United States National Institutes of Health; urologic; Woman
Relevance: New technologies with the ability to engineer implantable living tissues or encourage the regeneration of tissues and organs hold great promise for the treatment and cure of a variety of birth defects and other childhood afflictions. However, a surprisingly small fraction of tissue engineering research focuses on the needs of pediatric patients when compared to adult therapies. This proposed workshop aims to bring together engineers, scientists and clinicians involved in tissue engineering research and in treating pediatric patients with tissue engineering needs in order to motivate research in these areas and enhance collaboration
Project start date: 2011-12-06
Project end date: 2012-11-30
Budget start date: 6-DEC-2011
Budget end date: 30-NOV-2012
1R13HD071726-01 (2012): $16000
Sponsored Links Excellgen http://Excellgen.com
Grants awarded to Jane Kathryn
IMMUNE REGULATION OF NEURONAL INJURY AND REPAIR
Jane Kathryn, Professor And Chair
Indiana Univ-purdue Univ At Indianapoliscity: Indianapolis country: United States (us)
Grant 7R01NS040433-10 from National Institute Of Neurological Disorders And Stroke
Abstract: This is a revised competitive renewal application of a project based on our discovery of abeneficial role for the peripheral immune system in mouse facial motoneuron (FMN)reparative processes. In the initial funding period, the immune cellular and molecular components involved were identifiedthe CD4+ effector Th2 cell is necessary for FMN survival after facial nerve injury, via an antigen-dependent process requiring peripheral activation and central re-activation. & brain-derived neurotrophic factor (BDNF) is an essential molecule. Importantly, FACS analysis of lymph node cells taken from axotomized mice indicates that Thi/Th2 cytokine-secreting cells are generated in response to peripheral nerve injury. Functional recovery from facial paralysis induced by crush injury is impaired in immunodeficient mice, but can be restored to wildtype (WT) with immune reconstitution. It is hypothesizedthat CD4+effector T cells play distinct roles in motoneuron reparative processes, with the Tha cell mediating FMN survival through a central BDNF-dependent process and the Thi cell mediating functional recovery byparticipation in the lesion site pro-inflammatory response. 4 aims will test this hypothesis. Aim #1 is to determine the mechanism underlying CD4+ effector T cell localization within the facial motor nucleus after facial nerve injury. Experiments will utilize immunodeficient mice reconstituted with GFP-expressing CD4+Tcells, in sifu hybridization with Thi/Th2 cytokine riboprobes, chemokine RT- PCR, and chemokine neutralization antibodies/knockout mice. Aim #2.is to determine the mechanism underlying CD4+ T cell-mediated FMNsurvival after facial nerve injury, and will use WT and chimeric BDNF-negative mice to test the role of CD4+T cell-derived BDNF in FMNrescue. Aim #3 is to determineif immune cell-mediated rescue of cranial motoneurons (FMN)from axotomy-induced cell death can be generalized to a spinal MN. WT,immunodeficient,and reconstituted immunodeficientmicewill be used to determine the impact ofthe immune system on sciatic MNviability after sciatic nerve injury. Aim #4 is to determine if the Thi effector cell mediates functionalrecoveryfrom peripheral nerveinjury-induced paralysis. STAT4,T-bet, and STAT6deficient mice will be used with selective reconstitution experiments to determine the role of Thi/Th.2 effector cells in recovery of motor function, assessed with behavioral tests, after a facial or sciatic nerve crush injury. The immune system can have both protective and destructive effects in neural disease (such as amyotrophic lateral sclerosis, a fatal MNdisease) and/or trauma (such as spinal cord injury), but the regulatory nature ofsuch contradictory actions has yet to be determined. Understanding how the immune system benefits the injured nervous system holds great promise in the development of effective treatment strategies to offset disease or injury progression, and reduce disability
Keywords: ALS; Amyotrophic Lateral Sclerosis; Animals; Antibodies; Antigens; ATGN; axon regeneration; axonal regeneration; Axotomy; base; BDNF; behavior test; behavioral test; biological signal transduction; Blood - brain barrier anatomy; Blood-Brain Barrier; body system, allergic/immunologic; Brain Stem; Brain-Derived Neurotrophic Factor; Brainstem; CD4 lymphocyte; CD4 Positive T Lymphocytes; CD4 T cells; CD4+ T cell; CD4+ T-Lymphocyte; CD4-Positive Lymphocytes; Cell Communication and Signaling; Cell Count; Cell Death; Cell Nucleus; Cell Number; Cell Signaling; Cells; Cells, CD4; Cephalic; Cervical Lymph Node; Cervical lymph node group; chemoattractant cytokine; chemokine; chemokine receptor; Cranial; Cranial Nerve VII; Crush Injury; cytokine; Cytokines, Chemotactic; D12S1644; Development; disability; Disease; disease/disorder; Disorder; effective therapy; Effector Cell; experiment; experimental research; experimental study; Face; facial; Facial motor nucleus; Facial Nerve; Facial Nerve Injuries; facial nerve motor nucleus; Facial nerve nucleus; Facial Nerve Paralysis; Facial nerve structure; Facial Nerve Trauma; Facial Neuropathy, Traumatic; Facial Nucleus; Facial Palsy; Facial paralysis; functional recovery; Funding; Gehrig`s Disease; Genes; Goals; helper T cell; Hemato-Encephalic Barrier; Homologous Chemotactic Cytokines; IL-4-STAT; Immune; Immune system; immunocytochemistry; Immunodeficient Mouse; immunogen; In Situ; Inflammatory Response; injured; Injuries, Cranial Nerve VII; Injury; injury and repair; Intercrines; Intracellular Communication and Signaling; Investigation; Investigators; Kinetic; Kinetics; Knock-out; Knockout; Knockout Mice; Lesion; Lou Gehrig Disease; lymph gland; Lymph node proper; lymph nodes; Mammals, Mice; Mediating; MGC34632; Mice; Mice, Knock-out; Mice, Knockout; Modeling; Molecular; motoneuron; Motor; Motor Cell; Motor Neuron Disease, Amyotrophic Lateral Sclerosis; Motor Neurons; Murine; Mus; Myelopathy, Traumatic; Natural regeneration; Nature; necrocytosis; Nerve Crush; nerve injury; Nervous; Nervous System; Nervous system structure; neural; neural injury; Neurologic Body System; Neurologic Organ System; neuron injury; Neuronal Injury; neurotrophic factor; neurotrophin; neutrophin; NRVS-SYS; Nucleus; Null Mouse; organ system, allergic/immunologic; Palsy; Paralysed; paralysis; paralytic; Peripheral; Peripheral nerve injury; Play; Plegia; Process; programs; Programs (PT); Programs [Publication Type]; recombinase; reconstitute; reconstitution; Recovery; Recovery of Function; recruit; Recruitment Activity; regenerate; Regeneration; Regulation; relating to nervous system; Research Personnel; research study; Researchers; response; Reticuloendothelial System, Lymph Node; reverse transcriptase PCR; Reverse Transcriptase Polymerase Chain Reaction; Role; RT-PCR; RTPCR; sciatic nerve; Sciatic Nerve; selective expression; selectively expressed; Seventh Cranial Nerve; Seventh Cranial Nerve Injuries; Signal Transduction; Signal Transduction Systems; Signaling; SIS cytokines; Site; social role; sorting; Sorting - Cell Movement; Spinal; Spinal cord injured; Spinal cord injuries; Spinal cord injury; Spinal Cord Trauma; Spinal Trauma; Staining method; Stainings; Stains; STAT4; STAT4 gene; STAT6; STAT6 gene; STAT6B; STAT6C; Structure of sciatic nerve; T-Cell Subsets; T-Cells; T-Lymphocyte; T-Lymphocyte Subsets; T4 Cells; T4 Lymphocytes; Testing; Th-2 Cell; Th2 Cells; thymus derived lymphocyte; Thymus-Dependent Lymphocytes; Time; Transducers; Trauma; treatment strategy; Type 2 Helper Cell; Work
Project start date: 2000-07-01
Project end date: 2011-11-30
Budget start date: 1-DEC-2010
Budget end date: 30-NOV-2011
7R01NS040433-10 (2011): $342637
TISSUE ENGINEERING STRATEGIES: EFFECTS ON VALVULAR INTERSTITIAL CELL METABOLISM
Jane Kathryn, Assistant Professor
Rice Universitycity: Houston country: United States (us)
Grant 1R03EB011576-01A1 from National Institute Of Biomedical Imaging And Bioengineering
Abstract: PROJECT SUMMARY Principal Investigator Kathryn Jane Grande-Allen, Ph.D. Heart valve disease mandates hospitalization for almost 100,000 Americans every year. Although some of the initial causes of valve disease are well recognized, the intermediate cell-mediated disease mechanisms are largely unknown. The only effective treatment for most valve diseases is surgical repair or replacement; there are no medical or therapeutic treatments for the prevention or amelioration of valve disease. The drive to dissect potential disease mechanisms and develop new medical therapies has invigorated research in valve biology. This field is in its infancy, but has theless has witnessed many recent findings about contractile, synthetic, cell communication, adhesion, and signaling characteristics of valvular interstitial cells (VICs), especially as they relate to the tissue engineering of valves and the development of calcific aortic valve disease. theless, there has been scant investigation into the metabolism of valve cells. Although recent publications have addressed how oxygen diffusion and perfusion affects valve cells and tissue engineered valves, the topic of valvular cell metabolism remains largely unaddressed. Cells within normal adult valves maintain quiescence (even within such a mechanically active tissue), but show the capacity to become activated and alter their phenotype/behavior in response to various injury or disease conditions. This activation process is quite poorly characterized, leading to several questions about the fundamental metabolic rates of VICs under these quiescent and activated conditions. It is also unknown how this metabolic rate is influenced by the environment of the cell, meaning its pericellular matrix and level of mechanical or chemical stimulation. These issues are very important given the use of exogenous stimuli in the development of tissue engineered valves, and the roles of these factors in valve remodeling and disease progression. Indeed, metabolism is recognized as the first responder to environmental stresses for most cell types. To address these questions, this research proposes to determine the fundamental metabolic rates of VICs (Aim 1). The following 2 aims will examine the effect of cytokine and hypoxic stimulation (Aim 2) and mechanical stretch (Aim 3) on metabolic rates and metabolic gene expression by VICs. This research is significant because it will provide new and fundamental information about the metabolic rates of VICs under basal and stressed culture conditions, and will establish an important new direction in the field of valve cell biology. The resulting data will complement the work of other investigators examining oxygen consumption of VICs and valve leaflets, and will guide scientists and engineers developing tissue engineered valves. This work will also promote new avenues for valve disease research, since the valve cell responses (enabled by metabolism) likely contribute to disease progression, whether the initial cause was cardiac dilatation, infection, or a congenital malformation. Information about fatty acid metabolism would be relevant to the early stages of calcific aortic valve disease, since there is a growing incidence of this condition in the setting of obesity, diabetes, and metabolic syndrome. Public Health Relevance Principal Investigator Kathryn Jane Grande-Allen, Ph.D. Heart valve disease leads to hospitalization for almost 100,000 Americans every year, but the causes of heart valve disease are a mystery, especially because much of the behavior of heart valve cells has never been previously studied. This research will study the metabolism of heart valve cells, meaning how they use sugars, fatty acids, and lactate to create fuel for their activities such as migrating and making new proteins. This research will also examine how several conditions that are used to create tissue engineered heart valves affect this metabolism. This research is also relevant due to the growing incidence of aortic valve disease in the setting of obesity, diabetes, and metabolic syndrome
Keywords: Address; Adhesions; Adult; Affect; American; Anabolism; Anisotropy; aortic valve disorder; base; Behavior; Biology; Biomedical Engineering; Blood Vessels; Cardiac; Cardiovascular system; Cell Communication; Cell Culture Techniques; cell type; Cells; Cellular biology; Characteristics; Chemical Stimulation; Complement; Congenital Abnormality; cytokine; Data; Development; Diabetes Mellitus; Diffusion; Dilatation - action; Disease; Disease Progression; Doctor of Philosophy; effective therapy; emergency service/first responder; Engineering; Environment; Explosion; Extracellular Matrix; Extracellular Matrix Proteins; fatty acid metabolism; fatty acid oxidation; Fatty Acids; Feasibility Studies; flexibility; Frequencies (time pattern); Future; Gene Expression; Glucose; Glycolysis; Glycosaminoglycans; Goals; Heart Valve Diseases; Heart Valves; Hospitalization; Hyaluronan; Hypoxia; In Vitro; in vivo; Incidence; infancy; Infection; Injury; interstitial cell; Investigation; Knowledge; Measures; Mechanical Stimulation; Mechanics; Mediating; Medical; Metabolic; metabolic abnormality assessment; Metabolic syndrome; Metabolism; Methods; Microarray Analysis; Myocardium; novel; nutrient metabolism; Obesity; Operative Surgical Procedures; oxidation; Oxygen; Oxygen Consumption; Pattern; Perfusion; Phenotype; Prevention; Principal Investigator; Process; Production; Proteins; public health relevance; Publications; repaired; Research; Research Methodology; Research Personnel; response; Role; Scientist; Signal Transduction; Smooth Muscle Myocytes; Staging; Stimulus; Stress; stressor; Stretching; success; sugar; Testing; Therapeutic; Tissue Engineering; tissue support frame; Tissues; tool; Translating; Work
Relevance: Public Health Relevance Principal Investigator: Kathryn Jane Grande-Allen, Ph.D. Heart valve disease leads to hospitalization for almost 100,000 Americans every year, but the causes of heart valve disease are a mystery, especially because much of the behavior of heart valve cells has never been previously studied. This research will study the metabolism of heart valve cells, meaning how they use sugars, fatty acids, and lactate to create fuel for their activities such as migrating and making new proteins. This research will also examine how several conditions that are used to create tissue engineered heart valves affect this metabolism. This research is also relevant due to the growing incidence of aortic valve disease in the setting of obesity, diabetes, and metabolic syndrome
Project start date: 2011-06-01
Project end date: 2013-05-31
Budget start date: 1-JUN-2011
Budget end date: 31-MAY-2012
PFA/PA: PA-10-064
1R03EB011576-01A1 (2011): $76250
BIOMATERIAL STRATEGIES FOR TISSUE ENGINEERING PEDIATRIC VALVES
Jane Kathryn, Assistant Professor
Rice Universitycity: Houston country: United States (us)
Grant 1R21HL110063-01 from National Heart, Lung, And Blood Institute
Abstract: Heart defects occur in almost 1 percent of all live births and usually include abnormalities of the semilunar heart valves. Few options exist for treating valve defects; even so, these corrections are only palliative and do not preclude the need for re-operation on the valve later in the patient´s life. The prognosis for these patients would be revolutionized by the development of a living, autologous, pediatric tissue engineered heart valve (TEHV). A major hurdle in the development of TEHVs is creating a scaffold with valve-like material behavior and microstructure. Furthermore, most research on TEHVs has focused on achieving design goals that are appropriate for adult heart valves, not those of infants and children. The primary microstructural attributes of the semilunar heart valves (aortic and pulmonary) are their anisotropic nature and their layered structure, which provide valvular interstitial cells (VICs) with heterogeneous pericellular environments. These characteristics are by the polymer mesh scaffolds being investigated for TEHVs, and there is little consensus about optimal strategies to produce acellular leaflet scaffolds. Many groups including ours have investigated natural and synthetic gel-based scaffolds for studies of VIC biology and pathology, but these have generally seeded VICs within or atop homogeneous structures. Therefore, we hypothesize that novel hydrogel-based scaffolds can be prepared using biomaterial fabrication methods to generate TEHV scaffolds that mimic the complex structure, mechanical function, biological heterogeneity, and anti-thrombotic nature of pediatric semilunar valves. Hydrogel biomaterials are biocompatible, have tunable structure and mechanics, can be biofunctionalized, and can easily encapsulate cells. In addition, pediatric heart valves are distinct from adult valves on a mechanical, microstructural, and cellular basis. Furthermore, little is known about the endothelium of pediatric heart valves, even though an intact endothelium is considered necessary for success of TEHVs. Our lab is uniquely positioned to perform this research, as we have characterized age-related differences in valve mechanics and microstructure as well as of tissues and cells from congenitally malformed pediatric semilunar valves. We also have generated novel structures and regions of differential material behavior within PEGDA hydrogels. Our objective is to apply advanced biomaterial strategies for creating pediatric TEHVs. We propose to apply patterning and quasi-layering approaches to develop hydrogel TEHV biomaterial scaffolds with customized structural features that replicate the micro-architecture, material properties, mechanical function, and durability of pediatric semilunar valves (Aim 1). To promote a valve-like enthothelial coating of the pediatric TEHV, we will then evaluate the endothelial characteristics of pediatric semilunar valves and modify the scaffold surface (Aim 2). Employing these advanced hydrogel/biomaterial strategies will generate a novel TEHV scaffold that mimics the biological and mechanical heterogeneity of native semilunar valves, and hasten the translation of this life-changing therapy for pediatric patients with valvular heart disease. Heart valve defects are among the most common birth defects, but the available options for surgical repair of these valves are not ideal and require children to have repeat surgery every few years. We propose to develop a hydrogel-based scaffold to be used in tissue engineering a replacement heart valve for children with congenital valve defects. Our goal is to prepare this scaffold in such a way to recreate the complex structure of pediatric heart valves, test the durability of these scaffolds, and coat the surface of the scaffold with endothelial cells to prevent blood clots from forming
Keywords: Adult; age related; aortic valve disorder; Architecture; Autologous; base; Behavior; Biocompatible; Biocompatible Materials; Biological; Biological Process; Biomimetics; Bioprosthesis device; Blood; Blood Clot; Blood coagulation; Cardiopulmonary Physiology; Cardiovascular Physiology; Cells; Cellular biology; Characteristics; Child; Childhood; Climacteric; Complex; Congenital Abnormality; Congenital Heart Defects; Consensus; Defect; design; Development; Disease; Encapsulated; Endothelial Cells; Endothelium; Environment; Extracellular Matrix Proteins; Gel; Goals; Heart; Heart Valve Diseases; heart valve replacement; Heart Valves; hemodynamics; Heterogeneity; Hydrogels; Infant; interstitial cell; Life; Ligands; Live Birth; Lung; Mechanics; Methods; Nature; next generation; novel; operation; Operative Surgical Procedures; outcome forecast; palliative; Pathology; Patients; Pattern; Performance; poly(ethylene glycol)diacrylate; Polymers; Population; Positioning Attribute; prevent; Property; repaired; Repeat Surgery; Research; scaffold; semilunar valve; Stem cells; Structure; Structure-Activity Relationship; success; Surface; surface coating; Testing; Time; Tissue Engineering; Tissues; Translating; Translations
Relevance: Heart valve defects are among the most common birth defects, but the available options for surgical repair of these valves are not ideal and require children to have repeat surgery every few years. We propose to develop a hydrogel-based scaffold to be used in tissue engineering a replacement heart valve for children with congenital valve defects. Our goal is to prepare this scaffold in such a way to recreate the complex structure of pediatric heart valves, test the durability of these scaffolds, and coat the surface of the scaffold with endothelial cells to prevent blood clots from forming
Project start date: 2011-08-08
Project end date: 2013-07-31
Budget start date: 8-AUG-2011
Budget end date: 31-JUL-2012
PFA/PA: PA-10-010
1R21HL110063-01 (2011): $183680