Hypoxia leads to necrotic hepatocyte death

Hepatocyte transplantation is being investigated as a therapy for liver disease; however, its success has been limited by rapid death of the cells following transplantation. This study was dedicated to elucidating the mode of death responsible for loss of transplanted hepatocytes in order to guide future strategies for promoting their survival. Using a tissue engineering model, it was found that the environment within polymer scaffolds containing transplanted cells was hypoxic after 5 days in vivo , with (90 ± 3)% of hepatocytes existing at pO 2 < 10 mmHg. The primary mode of hepatocyte death in response to hypoxic conditions of 0 or 2 vol % oxygen was then determined in vitro . Several assays for features of apoptosis and necrosis demonstrated that hepatocytes cultured in an anoxic environment died via necrosis, while culture at 2% oxygen inhibited proliferation. These results suggest it will not be possible to prevent hepatocyte death by interfering with the apoptotic process, and hypoxic conditions in the transplants must instead be addressed. The finding that the environment within cell transplantation scaffolds is hypoxic is likely applicable to many cell-based therapies, and a similar analysis of the primary mode of death for other cell types in response to hypoxia may be valuable in guiding future strategies for their transplantation. © 2006 Wiley Periodicals, Inc. J Biomed Mater Res, 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55977/1/30930_ftp.pd

Facilitating Integrating Mission into the Classroom: Reaching Senior Faculty Members

Given the increasing challenges faced by institutions of higher education, Catholic colleges and universities are facing an increasing need to present clear, unique missions to their stakeholders. The development of a unique mission, however, is only the first step – truly integrating a mission into the institution’s activities is often easier said than done. This paper explores the activities by one Catholic university to integrate its mission into its classroom activities, with primary attention placed on a program (Xavier Mission Academy) targeted to senior faculty

Cyclic strain inhibits switching of smooth muscle cells to an osteoblastâ like phenotype

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154437/1/fsb2fj020459fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154437/2/fsb2fj020459fje-sup-0001.pd

A Biomimetic Approach for the Creation of Two-Dimensional Microscale Surface Patterns: Creation of Isolated Immunological Synapses

Current efforts in surface functionalization have not produced a robust technique capable of creating specific two-dimensional microscale geometrical arrays composed of multiple proteins. Such a capability is desirable for engineering substrates in sensing and cell patterning applications where at least two different protein functionalities in a specific configuration are required. Here we introduce a new approach for the creation of arrays of microscale geometries. We demonstrate our approach with a biomimetic structure inspired by the immunological synapse, a cell-cell interfacial structure characterized by two concentric rings of proteins: an outer adhesion protein structure and an inner recognition ligand core. The power of the technique lies in its ability to pattern any protein in any defined geometry as well as to create arrays in parallel

A Front Tracking Model of the MAXUS-8 Microgravity Solidification Experiment on a Ti-45.5at.% Al-8at.%Nb Alloy

On 26th March 2010 the MAXUS-8 sounding rocket was launched from the Esrange Space Center in Sweden. As part of the Intermetallic Materials Processing in Relation to Earth and Space Solidification (IMPRESS) project, a solidification experiment was conducted on a Ti-45.5at.%Al-8at.%Nb intermetallic alloy in a module on this rocket. The experiment was designed to investigate columnar and equiaxed microstructures in the alloy. A furnace model of the MAXUS 8 experiment with a Front Tracking Model of solidification has been developed to determine the macrostructure and thermal history of the samples in the experiment. This paper gives details of results of the front tracking model applied to the MAXUS 8 microgravity experiment. A model for columnar growth is presented and compared to experimental results for furnace A of the experiment module

Delivery of Hepatotrophic Factors Fails to Enhance Longer-Term Survival of Subcutaneously Transplanted Hepatocytes

Tissue engineering approaches have been investigated as a strategy for hepatocyte transplantation; however the death of a majority of transplanted cells critically limits success of these approaches. In a previous study, a transient increase in hepatocyte survival was achieved through delivery of vascular endothelial growth factor (VEGF) from the porous polymer scaffold utilized for cell delivery. To enhance longer-term survival of the hepatocytes, this delivery system was modified to additionally deliver epidermal growth factor (EGF) and hepatocyte growth factor (HGF) in a sustained manner. Hepatocytes were subcutaneously implanted in SCID mice on scaffolds containing EGF and/or HGF, in addition to VEGF, and survival was monitored for two weeks. A short-term enhancement of hepatocyte survival was observed after one week and is attributed to VEGF-enhanced vascularization, which was not altered by EGF or HGF. Surprisingly, long-term hepatocyte engraftment was not improved, as survival declined to the level of control conditions for all growth factor combinations after two weeks. This investigation indicates that the survival of hepatocytes transplanted into heterotopic locations is dependent on multiple signals. The delivery system developed for the current study may be useful in elucidating the specific factors controlling this process, and bring therapeutic transplantation of hepatocytes closer to implementation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63254/1/ten.2006.12.235.pd

Role of Vascular Endothelial Growth Factor in Bone Marrow Stromal Cell Modulation of Endothelial Cells

One of the fundamental principles that underlies tissue-engineering strategies using cell transplantation is that a newly formed tissue must acquire and maintain sufficient vascularization in order to support its growth. Enhancing angiogenesis through delivery of growth factors is one approach to establishing a vascular network to these tissues. In this study, we tested the potential of bone marrow stromal cells (BMSCs) to modulate the growth and differentiation activities of blood vessel precursors, endothelial cells (ECs), by their secretion of soluble angiogenic factors. The growth and differentiation of cultured ECs were enhanced in response to exposure to BMSC conditioned medium (CM). Enzyme-linked immunosorbent assays demonstrated that both mouse and human BMSCs secreted significant quantities of vascular endothelial growth factor (VEGF) (2.4-3.1 ng/106 cells per day). Furthermore, eliminating the activity of BMSC-secreted VEGF with blocking antibodies completely blocked the CM effects on cultured ECs. These data demonstrate that human BMSCs secrete sufficient quantities of VEGF to enhance survival and differentiation of endothelial cells in vitro, and suggest they may be capable of directly orchestrating angiogenesis in vivo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63256/1/107632703762687573.pd