What's Happening At The
McGowan Institute?

October 2006 | VOL. 5, No 10 | www.McGowan.pitt.edu

Studies find differentiated cells are more efficient than stem cells for somatic cell nuclear transfer

Dr ChengNew research dismisses the notion that adult stem cells are necessary for successful animal cloning, proving instead that cells that have completely evolved to a specific type not only can be used for cloning purposes, but they may be a better and more efficient starting point. In a study led by Xiangzhong (Jerry) Yang, Ph.D., of the University of Connecticut, and Tao Cheng, M.D., of the University of Pittsburgh, published in the journal Nature Genetics, the researchers report they created two mouse pups from a type of blood cell that itself is incapable of dividing to produce a second generation of its own kind.

This is the first demonstration that an animal can be derived directly from a fully differentiated cell; moreover, the researchers say results of their studies provide compelling evidence that Dolly the sheep and other mammals cloned by somatic cell nuclear transfer were most likely derived from fully differentiated cells, not adult stem cells, as most have argued in the nine years since Dolly was first created. Because stem cells have the ability to self-renew and differentiate into any specialized cell type, they have been heralded for their promise for treating a variety of diseases and conditions. Yet, even for cloning of an embryo to the blastocyst stage, from which embryonic stem cells can be generated, adult stem cells have yielded disappointing results, with success rates in the range of 1 to 5 percent.

In their studies, the researchers compared the efficiency for cloning mice using a fully differentiated blood cell called a granulocyte with its ancestor cells at different stages: hematopoietic stem cells, which are found in bone marrow and give rise to all red and white blood cells, and progenitor cells. Granulocytes are well characterized white blood cells unique for their segmented nuclei and the numerous granules in the cells’ cytoplasm.

Surprisingly, the granulocytes were the most efficient donor cells for nuclear transfer among the different lineage cells, with 35 to 39 percent becoming a blastocyst, an early embryo consisting of about 100 to 150 cells, compared to 11 percent for the progenitor cells and only 4 percent for the stem cells. Only the granulocytes were able to produce two live cloned pups, although both died within a few hours of birth. As a control, the researchers performed nuclear transfer using embryonic stem cells; 49 percent developed to the blastocyst stage and 18 cloned pups were born.

MORE

PITT TO RECEIVE $8.4 MILLION FROM NIH TO DETERMINE BEST TREATMENTS FOR SEPSIS

Dr AngusSepsis is among the top causes of death in the United States, affecting 750,000 Americans each year, of which 30 percent die. It also is one of the most expensive diseases, with a cost to U.S. hospitals of $17 billion each year. To investigate and determine the best methods for treating this life-threatening disease, the National Institute of General Medical Sciences (NIGMS) has awarded an $8.4 million, five-year grant to the University of Pittsburgh School of Medicine to head a multidisciplinary, multi-center consortium.

The Protocolized Care for Early Septic Shock (ProCESS) study will attempt to determine if there is a “golden hour” in the management of sepsis and septic shock when a prompt, rigorous, standardized treatment regimen can be used to improve clinical outcomes and halt the cascade of events that often lead to organ failure and death. The study takes a cue from the realm of coronary care, which has significantly reduced mortality from acute coronary diseases and dramatically reduced the costs of care by determining such best practices.

The investigators, led by Derek C. Angus, M.D., M.P.H., professor and vice chair of research, department of critical care medicine, School of Medicine, share a sense of urgency about their research. They hope that the project will generate useful and comprehensive data on the clinical and biological aspects of standardized treatment for septic shock – data that can have an immediate impact on and improve the care of the critically ill.

The trial, to be conducted at several leading hospitals around the country, will enroll up to 2,000 participants who present to the emergency department with septic shock. Participants will be randomized to receive alternative treatment protocols involving intravenous fluids, drugs that reverse the shock and hemodynamic monitoring during the first six hours of care. The protocols will be evaluated on three measures: clinical effectiveness as evidenced by improved mortality rates; effectiveness in reducing concentrations of biological markers that are associated with the four fundamental pathways of sepsis-related organ dysfunction – cellular hypoxia, oxidative stress, inflammation and coagulation/thrombosis; and cost effectiveness.

MORE

ADULT STEM CELLS TO REPAIR HEARTS

Dr LeeJoon Sup Lee, M.D. of the University of Pittsburgh School of Medicine is leading a novel clinical trial to study if a patient’s own stem cells can treat a form of severe coronary artery disease.

Dr. Lee plans to enroll 10 to 20 subjects in the study, known officially as the Autologous Cellular Therapy CD34-Chronic Myocardial Ischemia (ACT34-CMI) Trial. The ACTC34-CMI trial is the first human Phase II adult stem cell therapy study in the United States designed to investigate the efficacy, tolerability and safety of blood-derived selected CD34+ stem cells to improve symptoms and clinical outcomes in patients with chronic myocardial ischemia (CMI), a severe form of coronary artery disease.

ACT34-CMI is a prospective, randomized, double-blind, placebo-controlled study that involves adult patients with severe coronary artery disease who are currently on maximal medical therapy and are not suitable candidates for conventional procedures to improve blood flow to the heart, such as angioplasty, stents or coronary artery bypass surgery.

Dr. Lee’s study is one of 15 to 20 research sites nationwide participating in the study, which is sponsored by the Cellular Therapies business unit of the Baxter Healthcare Corporation. Baxter technology is used to select the patient’s own CD34+ stem cells that are under investigation in this trial.

MORE

STEM CELLS FROM FAT BEING STUDIED AS OPTION FOR BREAST RECONSTRUCTION

Dr RubinNIH has funded the University of Pittsburgh to explore unique stem cell and tissue engineering approach. Breast cancer survivors might one day avoid the prospect of invasive breast reconstruction surgery, opting instead for an approach that would involve using stem cells derived from their own fat, suggest University of Pittsburgh researchers who are studying the potential these cells may have for regenerating new breast tissue.

In animal models, the researchers hope to prove that an injection of fat-derived stem cells that are seeded onto microscopic scaffold structures will enable the production of a durable, replacement soft tissue. The team, led by J. Peter Rubin, M.D., assistant professor of plastic and reconstructive surgery, School of Medicine, recently received a three-year grant from the National Cancer Institute to further explore this unique approach.

The use of stem cells to treat disease or regenerate tissue is believed to hold promise because of their potential to develop into different specialized cell types. Indeed, when exposed to specific conditions in the laboratory, fat-derived stem cells have been shown to differentiate into cells characteristic of those from tissues such as fat, bone, cartilage, nerve, muscle and blood vessels.

Working with Dr. Rubin on the NIH-funded grant are co-investigators Kacey G. Marra, Ph.D., Albert D. Donnenberg, Ph.D., Vera S. Donnenberg, Ph.D., Stephen Badylak, D.V.M., M.D., Ph.D., and Howard D. Edington, M.D. 

MORE

GRANT RENEWED FOR SPINAL CORD INJURY RESEARCH CENTER

Dr BoningerThe University of Pittsburgh has received a $2.2 million grant from the National Institute on Disability and Rehabilitation Research (NIDRR) renewing funding for its University of Pittsburgh Model Center on Spinal Cord Injury (UPMC-SCI), which researches innovative assistive technologies that improve mobility and independence for people with spinal cord injuries.

The original funding for the UPMC-SCI was received in 2000. “Over the past six years, the Model Center has demonstrated a commitment to groundbreaking research that holds great promise for individuals with spinal cord injuries,” UPMC-SCI Director Michael Boninger, M.D., said.  “This continued funding will allow us to expand our efforts in several areas and evaluate patient data and outcomes more extensively, both here at Pitt as well as in multiple Model Centers throughout the country,” added Dr. Boninger, who also is professor and vice chair for research in the department of physical medicine and rehabilitation at the University of Pittsburgh School of Medicine.

MORE

SPINE RESEARCH LABORATORY

Dr KangThe Spine Research Laboratory, under the direction of James D. Kang, MD, is actively engaged in the development of novel cell and molecular biology based treatments of intervertebral disc degeneration. 

By way of background, preclinical feasibility studies of gene therapy for the treatment of disc degeneration established that viral vectors were successful in delivering exogenous marker genes to rabbit lumbar intervertebral discs in-vivo.  Delivery of hTGF-beta growth factor genes to the rabbit disc resulted in increased synthesis of a critical extracellular matrix component, proteoglycan, which is crucial for disc hydration and healthy function.  More recently, the laboratory has developed a rabbit model of intervertebral disc degeneration, with quantitative outcome measures: x-ray, MRI, histology, and gene expression.  Recent work [in press] has shown BMP-2 gene therapy results in preservation of MRI signal in this model. 

While the above studies used adenoviral vectors to establish feasibility and efficacy of gene transfer for the treatment of intervertebral disc degeneration, the Spine Research Laboratory—with an eye towards clinical translation—has performed extensive safety studies, and has developed an adeno-associated viral vector strategy which may be less immunogenic than the experimental adenovirus-based approaches (hence a better candidate for clinical translation. 

Parallel studies have been performed in-vitro using intervertebral disc cells cultured from surgical specimens—demonstrating that human disc cells are responsive to gene transfer.  Additional in-vitro studies of cells from degenerated human discs has established that increased proteoglycan synthesis can be achieved by gene transfer of the catabolic inhibitor TIMP-1.  Accordingly, the Spine Research Laboratory has established preliminary efficacy of pro-anabolic as well as anti-catabolic gene therapy strategies.  The latter strategy presents theoretical advantages over the former such as less nutritional demand, and is supported by previous studies showing that cells from degenerating discs produce elevated levels of catabolic agents that potentially could be blocked by an anti-catabolic gene transfer approach. 

The Spine Research Laboratory continues to assess the exciting potential of molecular approaches to the treatment of spinal disorders. 

RESEARCHERS RECEIVE $12.8 MILLION NIH GRANT TO IMPROVE DIAGNOSIS/TREATMENT OF CHRONIC LUNG DISEASE

Dr KollsChildren’s Hospital of Pittsburgh of UPMC and University of Pittsburgh School of Medicine researchers have been awarded a $12.8 million grant to improve the diagnosis and predict the therapeutic response of several devastating lung diseases.

This five-year grant from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) establishes Children’s and the University of Pittsburgh as a Specialized Center of Clinically Oriented Research (SCCOR) in Pediatric and Adult Pulmonology. This kind of center award is designed to facilitate more rapid translation of basic research findings into effective therapies for specific and troublesome diseases. Jay K. Kolls, MD, principal investigator and a professor of Pediatrics and Immunology at the University of Pittsburgh, and his collaborators not only hope to determine prevention strategies for patients suffering from allergic and fibrotic lung diseases, but also anticipate developing more effective treatments for these patients. The SCCOR consists of four research projects and two cores.
Hyperlink above

MORE

DR. BILLIAR ELECTED MEMBER TO INSTITUTE OF MEDICINE

Dr BilliarThe Institute of Medicine (IOM) has elected Timothy R. Billiar, M.D., the George V. Foster Professor of Surgery and chair of the department of surgery at the University of Pittsburgh School of Medicine, to its 2006 class. The 65 new members join the exclusive ranks of those whose contributions have advanced the fields of medical science and public health. Election is considered one of medicine’s highest honors.

Dr. Billiar is internationally renowned for his research that has brought significant understanding to the role that nitric oxide plays in the body’s response to septic shock, trauma and liver diseases. He holds six U.S. patents associated with his research, including one that he shares for the human inducible nitric oxide (iNOS) gene and a recombinant protein. His current research interest focuses on the mechanisms of trauma-induced organ damage due to inflammation. A practicing trauma and general surgeon, Dr. Billiar leads a department of surgery that ranks third in the nation among similar departments for National Institutes of Health-funded research.

MORE

MEDICAL DEVICE PIONEER SHARES 20 YEARS OF ACCOMPLISHMENTS

Dr BorovetzTwenty years ago, a pioneering team of clinicians and engineers had a vision to use a mechanical heart-assist device as an aid to a patient with a failing heart, and to ascertain if such a heart assist device could serve as a “bridge” for an ailing heart until a transplantable organ became available.

While the team consisted of many diverse disciplines, the lead biomedical engineer was Dr. Harvey Borovetz. Through the Regenerative Medicine Today podcast, in an interview with Leah Kauffman, Dr. Borovetz provides a retrospective look at the initial days of what has become a relatively routine clinical procedure to support a weakened heart with a ventricular assist device until a heart transplant can be implemented. Dr. Borovetz shares the progress that has been made over 20 years in the engineering as well as the clinical procedures.

He also provides a glimpse at the future, sharing his vision on the emerging technology development that he is leading to provide equivalent cardiac care for infants and children.

LISTEN TO THE INTERVIEW

DR. VORP ELECTED TO BMES BOARD

Dr VorpAssociate Professor of Bioengineering and Surgery Dr. David A. Vorp was elected to a 3-year term to the Board of Directors for the Biomedical Engineering Society.  Dr. Vorp also recently was named to the Executive Board of the Bioengineering Division of the American Society of Mechanical Engineers (ASME), and to the Executive Council of the International Society of Applied Cardiovascular Biology.  He also was named to the Editorial Board of the Journal of Biomechanics.

Dr. Vorp was recently awarded a $1.7 million grant from the NIH for the “Biomechanical Evaluation of Abdominal Aortic Aneurysm.”  The project will be funded over a five-year period.

WELCOME PROFESSOR FUCHS

Dr FuchsThe McGowan Institute joins in welcoming Julie Robin Fuchs, M.D. to Pittsburgh. Dr. Fuch's primary academic appointment is Assistant Professor of Surgery, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh.  Clinically, she serves as an Attending Surgeon, School of Medicine, Children's Hospital of Pittsburgh, Division of Pediatric Surgery.

Dr. Fuchs received her M.D. from Washington University School of Medicine, and served as a Research Fellow, in the Laboratory of Tissue Engineering and Organ Fabrication, under the leadership of Joseph P. Vacanti, M.D. Her training also included residencies in general surgery at the Harvard Medical School, Beth Israel Deaconess Medical Center, Chief Resident in General Surgery and Administrative Chief Resident in General Surgery at the Beth Israel Deaconess Medical Center, and served as a Fellow in Pediatric Surgery, Indiana University School of Medicine, J. W. Riley Hospital for Children.

MORE

DR. OGILVIE JOINS BIOENGINEERING DEPARTMENT

Jennifer B. Ogilvie, M.D. has received a secondary appointment in the Department of Bioengineering
Subject: Secondary in Bioengineering.  Her primary appointment is an Assistant Professor in the Department of Surgery, Division of Surgical Oncology, Section of Endocrine Surgery.

REGENERATIVE MEDICINE PODCASTS

The Regenerative Medicine Podcasts continue to be well received. There have been over 4,700 downloads to date. The most recent podcasts are:

Regenerative Medicine Today#18- Dr. Harvey Borovetz
Twenty years ago, a pioneering team of clinicians and engineers had a vision to use a mechanical heart-assist device as an aid to a patient with a failing heart, and to ascertain if such a heart assist device could serve as a “bridge” for an ailing heart until a transplantable organ became available.

While the team consisted of many diverse disciplines, the lead biomedical engineer was Dr. Harvey Borovetz.  In this interview, Dr. Borovetz provides a retrospective look at the initial days of what has become a relatively routine clinical procedure to support a weakened heart with a ventricular assist device until a heart transplant can be implemented. Dr. Borovetz shares the progress that has been made in the engineering as well as the clinical procedures.

In podcast #18, Dr. Borovetz also provides a glimpse at the future, sharing his vision on the emerging technology development that he is leading to provide equivalent cardiac care for infants and children.

#19- Dr. Robert Kormos
Our last podcast featured the bioengineer responsible for much of today’s artificial heart technology. Now meet Dr. Robert Kormos, a clinician who has used those artificial hearts to help people survive until donor hearts were available. Some patients even recovered enough heart function to eliminate the need for transplantation.

#20- Dr. William Wagner
Dr. Wagner is working to reconstruct damaged arteries and veins with scaffolds, and is leading a team that is developing a tissue engineered cardiac patch that could help to strengthen heart muscle that has been damaged by a heart attack.

Dr. Wagner also will tell us about his work to improve the interface between artificial devices and the body’s tissues, and about a new imaging technique his lab is working on that could help physicians view whether a transplanted heart has been rejected without performing a biopsy.

Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.

MOLECULAR ART NETWORKING SESSIONS

Patient SiteBased on the requests of faculty and graduate students for more and different types of networking sessions, the Moleculart project will continue in the Fall term. Our goal is to have a scientific gathering that fosters networking in a different environment. Please save the date and join us on December 6th;

  • December 6, 2006
    Artist: Laura Backman
    Time: 4:30 – 6:30 PM
    Place: S-100 BST

More

MCGOWAN INSTITUTE RETREAT-PLEASE SAVE THE DATE

On-Line Registration Will Be Available in January

McGowan Institute - 2007 Scientific Retreat
March 5 and 6, 2007

Nemacolin Woodlands Resort - Farmington, PA

ARTIFICIAL HEART PATIENTS REACH A COLLECTIVE CENTURY MILESTONE

Dr KormosThe University of Pittsburgh Medical Center (UPMC) Artificial Heart Program recently reached a new milestone. More than 350 patients who have received implants of various mechanical heart assist devices at UPMC within the past 21 years have together clocked more than a century that they have been supported by heart assist devices while awaiting transplantation. To celebrate the occasion, UPMC hosted the Heart of Pittsburgh Gala on Saturday, Oct. 14 at the West Club, Heinz Field.

“One hundred years is a wonderful milestone,” stated Robert Kormos, M.D., professor of surgery and director of the artificial heart program at UPMC. “Our heart assist devices have given new life and new hope to a broad range of patients. As the technology continues to evolve, this will provide new opportunities for resolving end-stage congestive heart failure. We are most excited at their potential for enhancing recovery of heart function following severe heart disease.”

In the 21 years that the UPMC program has been in existence, the longest that one of its patients was supported on a VAD was 670 days. The shortest period a patient was on a device was one day – a donor heart became available and organ transplantation was performed. About 75 percent of UPMC’s patients have been successfully “bridged” to transplant, meaning more than 200 patients who would have otherwise died without a heart transplant survived until a suitable heart was found. Ventricular assist devices have remarkably allowed 10 UPMC patients to regain heart function, making heart transplantation no longer necessary. 

MORE

PUBLICATION OF THE MONTH

Publication of the Month | October 2006
Author(s)

Li-Ying Sung1, 6, Shaorong Gao1, 6, Hongmei Shen2, Hui Yu2, Yifang Song2, Sadie L Smith1, Ching-Chien Chang1, Kimiko Inoue1, Lynn Kuo3, Jin Lian4, Ao Li5, X Cindy Tian1, David P Tuck5, Sherman M Weissman4, Xiangzhong Yang1 & Tao Cheng2

1-Center for Regenerative Biology and Department of Animal Science, University of Connecticut, Storrs, Connecticut 06269, USA.
2-Cancer Stem Cell Program, University of Pittsburgh Cancer Institute and Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
3-Department of Statistics, University of Connecticut, Storrs, Connecticut 06269, USA.
4-Department of Genetics, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
5-Department of Pathology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
6-These authors contributed equally to this work.

Title

Differentiated cells are more efficient than adult stem cells for cloning by somatic cell nuclear transfer

Summary

Since the creation of Dolly via somatic cell nuclear transfer (SCNT)1, more than a dozen species of mammals have been cloned using this technology2. One hypothesis for the limited success of cloning via SCNT (1%–5%)3 is that the clones are likely to be derived from adult stem cells4. Support for this hypothesis comes from the findings that the reproductive cloning efficiency for embryonic stem cells is five to ten times higher than that for somatic cells as donors5, 6 and that cloned pups cannot be produced directly from cloned embryos derived from differentiated B and T cells or neuronal cells7, 8, 9, 10. The question remains as to whether SCNT-derived animal clones can be derived from truly differentiated somatic cells. We tested this hypothesis with mouse hematopoietic cells at different differentiation stages: hematopoietic stem cells, progenitor cells and granulocytes. We found that cloning efficiency increases over the differentiation hierarchy, and terminally differentiated postmitotic granulocytes yield cloned pups with the greatest cloning efficiency.

Source

Nature Genetics - 38, 1323 - 1328 (2006)

GRANT OF THE MONTH

Grant of the Month | October 2006
PI

J. Peter Rubin, M.D.

Co-PIs Kacey G. Marra, Ph.D., Albert D. Donnenberg, Ph.D., Vera S. Donnenberg, Ph.D., Stephen Badylak, D.V.M., M.D., Ph.D., and Howard D. Edington, M.D.
Title

Stem Cells From Fat Being Studied As Option For Breast Reconstruction

Description

Breast cancer is endemic in the United States, with nearly 216,000 new cases expected this year (American Cancer Society statistics). For patients undergoing mastectomy, the loss of one or both breasts can cause significant discomfort and psychosocial distress. The number of breast reconstruction operations exceeds 80,000 cases per year (American Society of Plastic Surgeons statistics). Current surgical options including autologous tissue flaps and implants, have significant problems.

The use of adipose precursor cells, or preadipocytes, may represent a better solution for soft tissue reconstruction for cancer defects. We hypothesize that human preadipocytes can be seeded on microcarrier scaffolds and be injected into an animal model to produce a durable engineered soft tissue replacement. Furthermore, we speculate that the preadipocytes will deifferentiate into both adipocytes and elements of the new vascular system that perfuses the fat tissue.

The specific aims of this study are to:

  • Characterize cell surface markers of human preadipocytes using flow cytometry and assess the variability of differentiation of cloned subpopulations. Preadipocytes will be isolated from adipose tissue of breast cancer patients for clinical relevance.
  • Evaluate the adherence, proliferation and adipogenic differentiation of human preadipocytes within macroporous collagenous beads and small intestinal submucosa (SIS) microparticles in culture.
  • Determine the ability of human preadipocytes to generate mature adipose tissue when seeded in collagen and SIS particles and injected subcutaneously into a nude mouse.
Source NIH
Term 3 Years

CONTRIBUTIONS TO BMES ANNUAL MEETING

The annual fall meeting of the Biomedical Engineering Society (BMES) was held in Chicago in October 2006. Numerous members of the McGowan Institute and the Bioengineering department contributed to the success of the meeting; there were fifty papers on a wide range of topics presented by McGowan Institute faculty and/or trainees:

Thrombotic Complications Associated With The Berlin Heart Pediatric VAD
T.A. Snyder, P.D. Wearden, V.O. Morell, S.A. Webber, R.L. Kormos, S Winowich, and W.R. Wagner

The Use Of An Electrospun Elastomeric Scaffold As A Small Diameter Vascular Graft In A Rat Model
A. Nieponice, L. Soletti, J.J. Stankus, T.M. Maul, J. Guan, W.R. Wagner, and D.A. Vorp

PKC-Induced Troponin I Phosphorylation And The Dynamic Force-Length Relationship In Mouse Myocardium
S.H. Smith, J.A. Kirk and S.G. Shroff

Effect Of Altered Cardiac Waveform On The Hemodynamic Features Of Human Cerebral Aneurysms
H. Zakaria, H. Yonas, and A.M. Robertson

Multiscale Models Of Aortic Valve Mechanics And Mechano-Biology
M.S. Sacks, and D. Schmidt

In vivo Biocompatibility Assessment Of A Magnetically Levitated Pediatric Ventricular Assist Device
T.A. Snyder, C.A. Johnson, J.R. Woolley, P.D. Wearden, M.V. Kameneve, J.S. Richardson, A.J. Koert, and W.R. Wagner

Development Of Flow Cytometric Assays For Biocompatibility Assessment In Ovines
C.A. Johnson, T.A. Snyder, J.R. Woolley, and W.R. Wagner

Aortic Valve Interstitial Cell Mechanobiology: Response To Cyclic Tension And Tgf-1
W.D. Merryman, H.D. Lukoff, R.A. Long, G.C. Engelmayr, R.A. Hopkins, and M.S. Sacks

Pressure-Calcium Relationships In Perfused Mouse Hearts
J.A. Kirk, G.A. Macgowan, C. Evans, and S.G. Shroff

Interleukin-6 Stimulates Increased Superoxide Production Via NADPH Oxidase
C.H. Coyle, R. Kato, F. De Miguel, W.C. De Groat, M.B. Chancellor, and N. Yoshimura

Mn2+ Enhances Integrin 51 Binding Affinity By Resisting Ca2+ Induced Down Regulation
N.A. Perrusquia, H. Lin, and S.G. Shroff

Multivariate Cue-Signal-Response Analysis Of Tnf-Induced Hepatocyte Proliferation And Apoptosis
B.D. Cosgrove, D.B. Stolz, L.G. Griffith, and D.A. Lauffenburger

Conducting Polymer/Hydrogel-Based Skin Electodes For High Quality Multi-Channel EEG Acquisition
G. Justin, r. Wadhwa, K. Lesk, R. Sclabassi, M. Sun, and X.T. Cui

Design Of P-Selection-Targeted Ultrasound Contrast Agents Using Mathematical Modeling
E.M. Tom, S. Kilic, F.S. Villanueva, and W.R. Wagner

A Novel Clinical Cardiovascular Internship For Undergraduate BME Students
R. Schaub

Electrically Controlled Drug Release System Based On Electroactive Conducting Polymers
X.T. Cui

Whole Blood Biocompatibility Of A Hollow Fiber-Based Four Compartment Bioreactor
K.L. Gage, M.J. Baun, D.T. McKeel, M.S. Hout, and J.C. Gerlach

Role Of Contraction Dyssynchrony On Global Left Ventricular Mechanics And Performance
L. Johnson, H.K. Kim, M.P. Cannesson, S.G. Shroff, and M.R. Pinsky

Localized Thermal Phase Response Of Cellular Structures
C. Cheng and P. Leduc

Exploring Cellular Structures During Chemotaxis Via Semiconductor Quantum Dots And Microfluidics
L. Mays, A. Antunez De Mayolo, and P. Leduc

The Cardiologists Toolbox
M. Simon

Cell Based Cardiac Therapies
R.L. Kormos

Supporting The Failing Lung: The Need For New Strategies
W.J. Federspiel

Application Of Carbonic Anhydrase For Improved CO2 Gas Exchange In Artificial Lungs
H. Oh, J.L. Kaar, A.J. Russell, and W.J. Federspiel

Effects Of Decellularization On Mechanical And Structural Properties Of Porcine Aortic Valve Leaflet
E.M. Joyce, J. Liao, and M.S. Sacks

Biocompatibility Challenges In The Design Of A Pediatric VAD
W.R. Wagner

The Tandemheart Pediatric Ventricular Assist System
D.H. Wang, D. Smith, and R.G. Svitek

High Throughput Fabrication Of Polymeric Microparticles
S.R. Little

Specific Antibody Filter (SAF) For Removal Of Anti-A Antibodies For ABO-Incompatible Transplantation
E.M. Ciak, S. Gautam, A. Alikhani, and W.J. Federspiel

Design Of A Novel Scaffold For Autologous Stem Cells In Peripheral Nerve Tissue Engineering
L.E. Kokai, L. Santiago, J. Clavijo, L. Soletti, D.A. Vorp, J. Rubin, and K. Marra

Diabetes Induced Alternations In The Biomechanic Properties Of The Urinary Bladder Wall
C. Wang, J. Nagatomi, K. Toosi2, N. Yoshimura, M.B. Chancellor, and M.S. Sacks

Synergistic Effects Of EGF And Adhesion Ligands On Differentiation Of Mesenchymal Stem Cells
N.A. Marcantonio, A. Au, C.A. Boehm, A.M. Mayes, G.F. Muschler, A. Wells, and L. Griffith

Compressive Behavior Of Intraluminal Thrombi From Abdominal Aortic Aneurysms
F. Boschetti, M. Camera, R. Spirito, and E.S. Dimartino

Regional Dynamic Strains Of The Native Aortic Valve
D.M. Gaitan, P. Bienek, B. Zubiate, and M.S. Sacks

Probing Modalities Of Cytoskeletal Reorganization Under Mechanical Stimulation
K.S. Smith, K. Puskar, and P. Leduc

Utilizing Surface Plasmon Resonace To Increase Antibody Removal Of Specific Antibody Filters
Alikhani, N.V. Bovin, and W.J. Ferderspiel

PID Control Of An Ex-Vivo Vascular Perfusion System
M.S. El-Kurdi, J.S. Vipperman, and D.A. Vorp

Mathematical Model Of Adsorption Column Used Treatment Of Liver Failure
S.A. Safta, R. Miller, and J. Patzer II

Clustering Patters Of Erythrocyte Transmembrane Proteins Reveal Elements Of Mechanotransduction
I.Pagani, P. Leduc, and S.C. Watkins

Mechanotransduction Through Transmembrane Syndecan Proteins
J.D. Kubicek, H. Barnes, L. Duncan, A. Kamien, R. Bellin, and P. Leduc

Structural Constitutive Model Of The Urinary Bladder Wall With Basal Smooth Muscle Tone
S. Wognum and M.S. Sacks

Ex Vivo Alterations Of The Female Rat Urethra After Spinal Cord Injury
R. Prantil, W. De Groat, and D.A. Vorp

Applications Of Multiphase Computational Fluid Dynamics To Analyze Monocyte Adhesion
R.W. Lyczkowski, B.R. Alevriadou, M. Horner, C.B. Panchal, and S.G. Shroff

Bone Marrow Derived Cells Express More Collagen When Seeded On Elongated Small Intestine Submucosa
A.J. Almarza, G. Yang, T. Nguyen, S. Abramowitch, and S.L. Woo

Comparing The Remodeling Capabilities Of Aortic And Pulmonary Valve Interstitial Cells
W.D. Merryman, J. Liao, A. Parekh, J.E. Candiello, H. Lin, M.S. Sacks

Subspace System Identification Of An Ex-Vivo Vascular Perfusion System
M.S. El-Kurdi, J.S. Vipperman, and D.A. Vorp

Constitutive Models For Cell-Integrated Elastomeric Scaffolds For Soft Tissue Engineering
T. Courtney, J. Liao, J. Stankus, J. Guan, W.R. Wagner, and M.S. Sacks

Development Of Flexible Thermosensitive Hydrogels For Soft Tissue Engineering
J. Guan And W.R. Wagner

Fabrication Of A Cell Intergrated Tissue Engineered Vascular Graft
J. Stankus, L. Soletti, K.L. Fujimoto, J. Guan, D.A. Vorp, and W.R. Wagner

Gene Regulation By Controlled Release From A Biodegradable Poly(Ester Urethane) Urea
P. Ramaswami, J. Friz, D. Cress, J.Guan, and W.R. Wagner

Newsletter Comments or Questions:

McGowan@pitt.edu