The Experts below are selected from a list of 6867 Experts worldwide ranked by ideXlab platform
Lingjun Wang - One of the best experts on this subject based on the ideXlab platform.
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transplantation of isl1 cardiac progenitor cells in small intestinal submucosa improves infarcted heart function
Stem Cell Research & Therapy, 2017Co-Authors: Lingjun Wang, Elizabeth M Meier, Shuo Tian, Shaoxiang Xian, Zhong WangAbstract:Application of cardiac stem cells combined with Biomaterial Scaffold is a promising therapeutic strategy for heart repair after myocardial infarction. However, the optimal cell types and Biomaterials remain elusive. In this study, we seeded Isl1+ embryonic cardiac progenitor cells (CPCs) into decellularized porcine small intestinal submucosa extracellular matrix (SIS-ECM) to assess the therapeutic potential of Isl1+ CPCs and the biocompatibility of SIS-ECM with these cells. We observed that SIS-ECM supported the viability and attachment of Isl1+ CPCs. Importantly, Isl1+ CPCs differentiated into cardiomyocytes and endothelial cells 7 days after seeding into SIS-ECM. In addition, SIS-ECM with CPC-derived cardiomyocytes showed spontaneous contraction and responded to β-adrenergic stimulation. Next, patches of SIS-ECM seeded with CPCs for 7 days were transplanted onto the outer surface of infarcted myocardium in mice. Four weeks after transplantation, the patches were tightly attached to the surface of the host myocardium and remained viable. Transplantation of patches improved cardiac function, decreased the left ventricular myocardial scarring area, and reduced fibrosis and heart failure. Transplantation of Isl1+ CPCs seeded in SIS-ECM represents an effective approach for cell-based heart therapy.
David L Kaplan - One of the best experts on this subject based on the ideXlab platform.
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multi layered silk film coculture system for human corneal epithelial and stromal stem cells
Journal of Tissue Engineering and Regenerative Medicine, 2018Co-Authors: Emily A Gosselin, Tess Torregrosa, Chiara E Ghezzi, Alexandra C Mendelsohn, Rachel Gomes, James L Funderburgh, David L KaplanAbstract:With insufficient options to meet the clinical demand for cornea transplants, one emerging area of emphasis is on cornea tissue engineering. In the present study, the goal was to combine the corneal stroma and epithelium into one co-culture system, in order to monitor both human corneal stromal stem cell (hCSSC) and human corneal epithelial cell (hCE) growth and differentiation into keratocytes and differentiated epithelium in these 3D tissue systems in vitro. Co-culture conditions were first optimized, including the medium, air/liquid interface culture, and surface topography and chemistry of Biomaterial Scaffold films based on silk protein. The silk was used as Scaffolding for both stromal and epithelial tissue layers because it is cell compatible, can be surface patterned, and is optically clear. Next, the effects of proliferating and differentiating hCEs and hCSSCs in this in vitro system were studied, including the effects on cell proliferation, matrix formation by immunochemistry, and gene expression by RT-qPCR. The incorporation of both cell types into the co-culture system demonstrated more complete differentiation and growth for both cell types compared to the corneal stromal cells and corneal epithelial cells alone. Silk films for corneal epithelial culture were optimized to combine a 4.0 micron-scale surface pattern with bulk-loaded collagen type IV. Differentiation of each cell type was in evidence based on increased expression of corneal stroma and epithelial proteins and transcript levels after 6 weeks in co-culture on the optimized silk Scaffolds. This article is protected by copyright. All rights reserved.
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a silk based Scaffold platform with tunable architecture for engineering critically sized tissue constructs
Biomaterials, 2012Co-Authors: Lindsay S Wray, Jelena Rnjakkovacina, Biman B Mandal, Daniel Schmidt, David L KaplanAbstract:In the field of tissue engineering and regenerative medicine there is significant unmet need for critically-sized, fully degradable Biomaterial Scaffold systems with tunable properties for optimizing tissue formation in vitro and tissue regeneration in vivo. To address this need, we have developed a silk-based Scaffold platform that has tunable material properties, including localized and bioactive functionalization, degradation rate, and mechanical properties and that provides arrays of linear hollow channels for delivery of oxygen and nutrients throughout the Scaffold bulk. The Scaffolds can be assembled with dimensions that range from millimeters to centimeters, addressing the need for a critically-sized platform for tissue formation. We demonstrate that the hollow channel arrays support localized and confluent endothelialization. This new platform offers a unique and versatile tool for engineering ‘tailored’ Scaffolds for a range of tissue engineering and regenerative medicine needs.
Sarah C Heilshorn - One of the best experts on this subject based on the ideXlab platform.
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Biomaterial design strategies for the treatment of spinal cord injuries
Journal of Neurotrauma, 2010Co-Authors: Karin S Straley, Cheryl Wong Po Foo, Sarah C HeilshornAbstract:The highly debilitating nature of spinal cord injuries has provided much inspiration for the design of novel Biomaterials that can stimulate cellular regeneration and functional recovery. Many experts agree that the greatest hope for treatment of spinal cord injuries will involve a combinatorial approach that integrates Biomaterial Scaffolds, cell transplantation, and molecule delivery. This manuscript presents a comprehensive review of Biomaterial-Scaffold design strategies currently being applied to the development of nerve guidance channels and hydrogels that more effectively stimulate spinal cord tissue regeneration. To enhance the regenerative capacity of these two Scaffold types, researchers are focusing on optimizing the mechanical properties, cell-adhesivity, biodegradability, electrical activity, and topography of synthetic and natural materials, and are developing mechanisms to use these Scaffolds to deliver cells and biomolecules. Developing Scaffolds that address several of these key design parameters will lead to more successful therapies for the regeneration of spinal cord tissue.
Stephanie M. Willerth - One of the best experts on this subject based on the ideXlab platform.
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Biomaterial Strategies for Delivering Stem Cells as a Treatment for Spinal Cord Injury.
Cells tissues organs, 2016Co-Authors: Andrew Agbay, John M. Edgar, Meghan Robinson, Tara Styan, Krista Wilson, Julian Schroll, Nima Khadem Mohtaram, Martin B.g. Jun, Stephanie M. WillerthAbstract:Ongoing clinical trials are evaluating the use of stem cells as a way to treat traumatic spinal cord injury (SCI). However, the inhibitory environment present in the injured spinal cord makes it challenging to achieve the survival of these cells along with desired differentiation into the appropriate phenotypes necessary to regain function. Transplanting stem cells along with an instructive Biomaterial Scaffold can increase cell survival and improve differentiation efficiency. This study reviews the literature discussing different types of instructive Biomaterial Scaffolds developed for transplanting stem cells into the injured spinal cord. We have chosen to focus specifically on Biomaterial Scaffolds that direct the differentiation of neural stem cells and pluripotent stem cells since they offer the most promise for producing the cell phenotypes that could restore function after SCI. In terms of Biomaterial Scaffolds, this article reviews the literature associated with using hydrogels made from natural Biomaterials and electrospun Scaffolds for differentiating stem cells into neural phenotypes. It then presents new data showing how these different types of Scaffolds can be combined for neural tissue engineering applications and provides directions for future studies.
Lonnie D. Shea - One of the best experts on this subject based on the ideXlab platform.
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Lentiviral Interleukin-10 Gene Therapy Preserves Fine Motor Circuitry and Function After a Cervical Spinal Cord Injury in Male and Female Mice
Neurotherapeutics, 2020Co-Authors: Jessica Y. Chen, Paras R. Patel, Alexander J. Hostetler, Hasan A. Sawan, Kayla A. Moss, Sarah E. Hocevar, Aileen J. Anderson, Cynthia A. Chestek, Lonnie D. SheaAbstract:In mammals, spinal cord injuries often result in muscle paralysis through the apoptosis of lower motor neurons and denervation of neuromuscular junctions. Previous research shows that the inflammatory response to a spinal cord injury can cause additional tissue damage after the initial trauma. To modulate this inflammatory response, we delivered lentiviral anti-inflammatory interleukin-10, via loading onto an implantable Biomaterial Scaffold, into a left-sided hemisection at the C5 vertebra in mice. We hypothesized that improved behavioral outcomes associated with anti-inflammatory treatment are due to the sparing of fine motor circuit components. We examined behavioral recovery using a ladder beam, tissue sparing using histology, and electromyogram recordings using intraspinal optogenetic stimulation at 2 weeks post-injury. Ladder beam analysis shows interleukin-10 treatment results in significant improvement of behavioral recovery at 2 and 12 weeks post-injury when compared to mice treated with a control virus. Histology shows interleukin-10 results in greater numbers of lower motor neurons, axons, and muscle innervation at 2 weeks post-injury. Furthermore, electromyogram recordings suggest that interleukin-10-treated animals have signal-to-noise ratios and peak-to-peak amplitudes more similar to that of uninjured controls than to that of control injured animals at 2 weeks post-injury. These data show that gene therapy using anti-inflammatory interleukin-10 can significantly reduce tissue damage and subsequent motor deficits after a spinal cord injury. Together, these results suggest that early modulation of the injury response can preserve muscle function with long-lasting benefits.
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Evaluation of Biomaterial Scaffold delivery of IL-33 as a localized immunomodulatory agent to support cell transplantation in adipose tissue.
Journal of immunology and regenerative medicine, 2018Co-Authors: Jeffrey M.h. Liu, Xiaomin Zhang, Shelby Joe, Xunrong Luo, Lonnie D. SheaAbstract:Abstract Introduction The development of novel immunomodulatory strategies that might decrease the need for systemic immune suppression would greatly enable the utility of cell-based therapies. Cell transplantation on Biomaterial Scaffolds offers a unique opportunity to engineer a site to locally polarize immunogenic antigen generation. Herein, we investigated the localized delivery of IL-33, which is a novel cytokine that has been shown to have beneficial immunomodulatory effects in certain transplant models as mediating anti-inflammatory properties in the adipose tissue, to determine its feasibility for use as an immunomodulatory agent. Results Localized IL-33 delivery from poly(lactide-co-glycolide) (PLG) Scaffolds implanted into the epididymal fat specifically increased the Foxp3+ population of CD4+ T cells in both blank Scaffold implants and Scaffolds seeded with allogeneic islets. In allogeneic islet transplantation, we found IL-33 delivery results in a local upregulation of graft-protective T cells where 80% of the local CD4+ population is Foxp3+ and overall numbers of graft destructive CD8+ T cells are decreased, resulting in a prolonged graft survival. Interestingly, local IL-33 also delayed islet engraftment by primarily inducing a local upregulation of Th2 cytokines, including IL-4 and IL-5, leading to increased populations of ST2+ Type 2 innate lymphoid cells (ILC2s) and Siglec F+ eosinophils. Conclusions These results suggest that local IL-33 delivery from Biomaterial Scaffolds can be used to increase Tregs enriched in adipose tissue and reduce graft-destructive T cell populations but may also promote innate cell populations that can delay cell engraftment.
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Biomaterial Scaffolds for localized IL-33 release to modulate the local immune environment and enhance extrahepatic allogeneic islet transplant
Journal of Immunology, 2017Co-Authors: Jeffrey M.h. Liu, Xiaomin Zhang, Xunrong Luo, Lonnie D. SheaAbstract:Allogeneic islet transplantation represents a promising therapeutic option to restore endogenous insulin production in Type-1 diabetes patients. Clinically, new methods of regulating the immune response against the islet allograft without using general immunosuppression are required. We have previously demonstrated the viability of transplanting syngeneic islets on porous poly-lactide-co-glycolide (PLG) Scaffolds within the epididymal fat pad to restore long-term euglycemia. The use of a Biomaterial Scaffold also provides an opportunity to incorporate novel immunomodulatory factors that can modify the local immune response to transplanted cells. Due to the prevalence of ST2+ regulatory T cells and M2 macrophages linked to promotion of an anti-inflammatory phenotype within adipose tissue, we hypothesized Scaffold-mediated IL-33 release could promote a tolerogenic environment to extend islet allograft survival. We found incubation of an IL-33 loaded Scaffold in vitro with naive T cells undergoing anti-CD3 TCR stimulation stimulated release of IL-13, demonstrating maintenance of IL-33 bioactivity. We found that IL-33 loaded Scaffolds implanted into the epididymal fat pad expanded the CD4+ Foxp3+ population within the graft site, most strikingly amongst CD4+ Foxp3+ ST2+ Tregs. Using an allogeneic murine islet transplant model, preliminary data showed diabetic C57BL/6 recipients receiving 250 Balb/c islets on IL-33 Scaffolds had extended graft survival time compared to BSA-loaded control Scaffolds. Collectively, these results indicate the potential for IL-33 to modulate the local immune response to support graft function, and support ongoing studies to investigate mechanisms to extend graft survival.
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Biomaterial Scaffolds for Controlled, Localized Gene Delivery of Regenerative Factors.
Advances in wound care, 2013Co-Authors: Robert Michael Gower, Lonnie D. SheaAbstract:Significance: Biomaterials play central roles in tissue regeneration by maintaining a space for tissue growth and facilitating its integration with the host. The regenerative capacity of materials can be enhanced through delivery of factors that promote tissue formation. Gene delivery is a versatile strategy to obtain sustained production of tissue inductive factors. Biomaterial Scaffolds capable of gene delivery have been shown to induce transgene expression and tissue growth. Critical Issues: The widespread application of Biomaterial Scaffold systems requires identifying the design principles for the material and vectors that modulate transgene expression temporally and spatially. These technologies and others will ultimately enable spatial and temporal control over expression to recreate the cellular organization and gene expression required for formation of complex tissues. Recent Advances: The design parameters for the Biomaterials and vectors that modulate the extent and duration of transgene expres...