McGowan Institute?
June 2009 | VOL.8, NO. 6 | www.McGowan.pitt.edu
Gift to Support Efforts to Cure Blindness Announced at Open Meeting
The McGowan Institute for Regenerative Medicine held its inaugural open meeting on Thursday, June 18, 2009. The purpose of the event was twofold: to highlight some of the Institute’s recent research accomplishments and share a vision for the future of regenerative medicine, and to announce the establishment of the Louis J. Fox Center for Vision Restoration.
Over 125 guests attended the open meeting. The Center for Vision Restoration of UPMC and the University of Pittsburgh today announced a $3 million gift from Louis J. Fox, a Pennsylvania native and Pitt graduate. UPMC has pledged to match Mr. Fox’s donation to the Center. Included in the meeting was a demonstration of the BrainPort, an investigational device that aims to give visual cues through non-visual neural pathways. The BrainPort vision device is an investigational non-surgical assistive visual prosthetic device that translates information from a digital video camera to your tongue, through gentle electrical stimulation.
“This generous gift by Mr. Fox will aid us in our efforts to pioneer comprehensive, patient-driven research and clinical therapies to treat people who, through disease, accident, or injury, have limited sight. To honor his generosity, the Center will now be known as the Louis J. Fox Center for Vision Restoration,” said McGowan Institute faculty member and Center executive director Maj. Gen. (retired) Gale Pollock, who, as former Deputy Surgeon General of the U.S. Army, recognized the need to find ways to restore lost vision.
Cpl. Mike Jernigan, a medically retired Marine who lost both eyes after being wounded by a roadside bomb in Iraq in 2004, demonstrated the use of BrainPort, an investigational device that is being studied at the Louis J. Fox Center for Vision Restoration. BrainPort aims to give back sight through non-visual neural pathways. The BrainPort vision device is an investigational non-surgical assistive visual prosthetic device that translates information from a digital video camera to your tongue, through gentle electrical stimulation. The body then sends signals to the brain that translates the signals into visual-like clues.
The Louis J. Fox Center for Vision Restoration is a comprehensive, multi-disciplinary research and clinical program dedicated to ocular regenerative medicine and improving the quality of life for the vision-impaired. A joint program of the UPMC Eye Center and McGowan Institute for Regenerative Medicine, the Fox Center’s main focus is discovery and development of new cures for blindness and visual impairment, especially for those with problems affecting the retina, optic nerve, cornea, and lens. Through basic and clinical research, it will provide vision restoration through the augmentation of existing visual pathways or by providing vision through non-visual means.
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McGowan Institute for Regenerative Medicine faculty member Peter Wearden, MD, PhD, assistant professor of cardiothoracic surgery at the University of Pittsburgh School of Medicine and pediatric cardiothoracic surgeon and director of pediatric mechanical cardiopulmonary support at Children’s Hospital of Pittsburgh of UPMC, is one of the leaders of Children’s Hospital Heart Center Team. Children’s Hospital is an acknowledged world leader in pediatric heart transplantation. The Heart Center Team fields requests for admission from around the country - and the world.
For some of Children’s patients, heart transplantation may not be necessary. The Heart Center Team agrees that the first goal is to do whatever you can with the patient’s current heart, either medically or surgically. Today, in some cases the use of ventricular assist devices (VADs) serve as a bridge to recovery instead, eliminating the potential issues related to heart transplantation. VADs offer great promise as a bridge to recovery, or as a bridge to a heart transplant.
"If you break a leg or arm, you rest it. But the heart and lungs can't rest," explains Dr. Wearden. "So if we have devices that can allow them to rest, they may have a chance to recover."
A scientific consortium led by Dr. Wearden, and including device manufacturer Levitronix LLC, received a $2.3 million National Heart Lung and Blood Institute Small Business Innovation Research (SBIR) grant to complete development of, and to clinically test, the first external centrifugal pump designed specifically for infants and small children in heart failure. Dr. Wearden hopes to begin clinical trials of the device, dubbed PediaVAS, this year.
Research continues on the development of a totally implantable pediatric VAD. That effort with partners including Carnegie Mellon University and the McGowan Institute has also received NIH funding. This project is developing a magnetically powered device the size of a AA battery dubbed PediaFlow, which could support a child for as long as 6 months.
Photograph: Dr. Peter Wearden holds two implantable heart pumps. At top is a prototype called the PediaFLOW, which is a compact version of the bottom pump. The pump on the right is an external pump called the PediaVAS, which Dr. Wearden hopes will replace a rolling cart-style pump used in hospitals. J.C. Schisler/Tribune-Review.
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McGowan Institute for Regenerative Medicine faculty member Kacey Marra, PhD, Director, Tissue Engineering Lab--Plastic Surgery Research, and Associate Professor, Department of Surgery, University of Pittsburgh, and a team of scientists at Pitt recently concluded a study to determine if guided fat (adipose) precursor cells (APCs) could improve nerve regeneration and functional recovery. In their work, the researchers used biodegradable nerve guides to transplant APCs into the injured peripheral nerves of laboratory rats.
"Adipose tissues, shown to be multipotent, have also been shown to be an abundant source of post-natal precursor cells that are relatively easy to isolate from fat tissue and in sufficient amounts to be injected immediately post-isolation," said Dr. Marra.
Adipose precursor cells, said Dr. Marra and co-authors, have demonstrated an ability to differentiate in vitro into cartilage (chondrogenic), bone (osteogenic), fat (adipogenic), and muscle (myogenic) cell types.
The researchers noted that the "gold standard" for nerve repair is the autograft to repair nerve gaps. Pre-clinical studies have shown that including Schwann cells within nerve conduits can enhance nerve regeneration. However, the incorporation of Schwann cells requires a second surgery, renders a secondary nerve nonfunctional, and requires Schwann cells in high numbers that are clinically challenging to obtain.
According to the researchers, significant differences in the sciatic functional index (SFI) were observed 3 weeks post-injury in the autografted, APC-transplanted group using nerve guides over a control group in which nerve guides were left empty. Researchers also observed the formation of a more robust nerve accompanied by modestly decreased muscle atrophy in the APC-transplanted group. No differences were observed after 12 weeks, however.
"We found that full regeneration of the sciatic nerve occurred in the rats receiving the autograft, the guide, and the guide loaded with APCs. No regeneration was observed in any of the rats in which the defect was left untreated," said Dr. Marra.
Their results also showed that transplanted human-derived APCs survived for up to 12 weeks in the injured peripheral nerve and formed a more robust nerve with nerve cells more than double the size of those formed using the conduit alone.
Read more. . .
McGowan Institute for Regenerative Medicine faculty member William Federspiel, PhD, William Kepler Whiteford Professor of Chemical Engineering, Surgery and Bioengineering, University of Pittsburgh, and Director of the McGowan Institute’s Medical Devices Laboratory, is a partner in a $1.9 million award from the National Heart, Lung and Blood Institute of the National Institutes of Health (NIH) to develop a groundbreaking blood-storage system. The project aims to advance New Health Sciences Inc.’s (NHSi) Hemanext Anaerobic Storage Platform (illustrated), which delivers higher quality blood for transfusion therapy and extends the shelf life of blood for transfusion. NHSi has demonstrated that this new technology can deliver higher-quality, more physiologic blood, with an improved capacity to deliver oxygen and more deformable red blood cells for better capillary perfusion, and extend by 50 percent or more the shelf life of stored red blood cells.
The 2-year Small Business Innovation Research Phase II grant from NIH follows a 2007-2008 Phase I grant of $133,290. “This grant is a major step forward for transfusion medicine,” NHSi President Martin Cannon said. “Evidence is mounting that, following transfusions, patients experience a multitude of complications resulting in increased morbidity and longer hospital stays that might have been prevented had better stored, better transported, and better preserved blood been used.”
Research has documented that the rate of complications increases with the number of units of blood transfused. Moreover, in a relatively large study, significantly worse post-operative outcomes were associated with blood stored longer than 15 days. The project partners expect widespread adoption of its new technology which will reduce the adverse side effects of life-saving blood transfusions and streamline blood-bank operations—alleviating periodic blood shortages and increasing pre-operative autologous (self-donated) blood donations.
“This research represents a paradigm shift in the approach to storage of red cells, the most significant change since the introduction of additive solutions 25 years ago,” Professor James AuBuchon of the University of Washington and President and CEO of the Puget Sound Blood Center, said.
Other partners in this effort to develop this new technology include Filtertek Inc. of Hebron, Illinois, and Multisorb Technologies of Buffalo, New York.
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McGowan Institute for Regenerative Medicine faculty member James Luketich, M.D., Co-Director of Surgical Affairs at the University of Pittsburgh Cancer Institute and the Sampson Family Endowed Chair in Thoracic Oncology at the University of Pittsburgh School of Medicine, is the head of an on-going clinical trial of a new medical device for the treatment of gastroesophageal reflux disease (GERD). The LINX™ Reflux Management System is an investigational device designed to restore the function of the Lower Esophageal Sphincter, preventing reflux and many of the symptoms that accompany it.
In patients with GERD the natural barrier has lost its muscular tone necessary to keep the contents of the stomach from routinely "refluxing" into the esophagus. This reflux is responsible for the discomfort of heartburn. More importantly, it can damage the walls of the esophagus and lead to more serious conditions such as esophagitis and Barrett's esophagus.
"On a good day, your valve opens for food and closes after you have eaten," said Dr. Luketich. "It prevents heartburn."
Dr. Luketich said that for millions of Americans, the valve malfunctions, usually after meals. So, instead of staying closed, it intermittently will leak, and that allows the acid to come back into the esophagus.
The LINX™ device is made of titanium beads that are linked together to take the shape of a small bracelet. Each of these beads contains a magnetic core that attracts it to the beads next to it.
Using a surgical technique called laparoscopy, the LINX™ device is placed around the esophagus in the area of the Lower Esophageal Sphincter. Once in place, the magnetic attraction between the beads may help support the esophagus to prevent reflux episodes.
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Technology developed by McGowan Institute Deputy Director Stephen Badylak, DVM, PhD, MD, Professor in the University of Pittsburgh Department of Surgery and Director of the Center for Pre-Clinical Tissue Engineering within the Institute, is being used in a study managed by Steven Wolf, MD, U.S. Army Institute for Surgical Research in San Antonio. The study is assessing the feasibility of restoring some function to the hands of soldiers who have suffered significant finger loss. Through regenerative medicine research and the studies that the Army is conducting at the Institute for Surgical Research, there is hope that some functionality can be added to the hands of some of our brave, wounded warriors.
As an international expert in regenerative medicine and the principal investigator of numerous research projects, Dr. Badylak was recently interviewed by Anne Underwood, Newsweek, about the efforts of the Armed Forces Institute of Regenerative Medicine research program. An excerpt of that conversation follows:
NEWSWEEK: Your work sounds like science fiction.
Stephen Badylak: Starfish, salamanders, and newts can regrow a lost limb. Human fetuses can also regenerate many structures during the early stages of fetal development. But that ability diminishes or disappears by the time we're born. The question is why, because the information is still there in our DNA. We want to resurrect fetal wound healing.
NW: Tell me about your work with AFIRM.
SB: Because of improvised explosive devices, soldiers are returning from Iraq and Afghanistan with lost fingers, lost hands, lost limbs. The only treatment options now involve prosthetic devices. For a 20-year-old, the rest of life is impacted in a negative way. The Defense Department is approaching this in a Manhattan Project mode. It's put $100 million on the table to address these horrific problems from a regenerative-medicine standpoint.
NW: Will you really be able to regrow fingers and limbs?
SB: In the foreseeable future, I doubt it. Fingers and limbs are very complex. They include nerves, bone, skin, muscle, and blood vessels. They're also large. Limb formation in a fetus is on a scale of a few millimeters. In a human, you're talking 20 pounds of flesh and bones.
NW: But you've been able to regrow large portions of muscle.
SB: A soldier in Texas had been injured by an explosive device in Afghanistan and lost a large portion of muscle in the upper portion of his leg. This loss significantly compromised his strength and range of motion and his ability to engage in normal activities. We helped regenerate a portion of that muscle, which is amazing. That never happens spontaneously. Over the next year, we'll treat another 8 to 10 soldiers.
NW: How much of the muscle has grown back?
SB: The results might be considered modest by some standards, but they're significantly better than anything tried before. He's had maybe a 12-percent increase in muscle mass, as measured by CT scan, and a 7- to 10-percent increase in strength over a 2-month period. He wants a second procedure.
NW: What made him a good candidate for this treatment?
SB: The part of the muscle at the hip was intact, and the part at the knee was intact, so we were just replacing the section in between. Once you get the process started, the body takes over.
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McGowan Institute for Regenerative Medicine faculty member Derek Angus, MD, professor and chair in the Department of Critical Care Medicine at the University of Pittsburgh School of Medicine, was the principal investigator of the study which showed important implications for understanding sex differences in life expectancy. The findings indicated the differing biological response to infection between men and women which may explain higher death rates among older men who are hospitalized with community-acquired pneumonia (CAP).
The researchers measured blood levels of inflammatory indicators, including tumor necrosis factor (TNF) and interleukins 6 and 10, coagulation indicators including Factor IX, and fibrinolysis indicators including D-dimer concentrations. They found patterns in these biomarkers that suggest men generate a stronger inflammatory and coagulation response and, perhaps, break up blood clots more quickly than women in response to infection.
Data were gathered from the multicenter Genetic and Inflammatory Markers of Sepsis (GenIMS) study. Participants were enrolled upon emergency department admission at 28 academic and community hospitals in Pennsylvania, Connecticut, Michigan, and Tennessee from 2001 to 2003. The study included 2,320 subjects, with a mean age of 64.9 years, 1,136 of whom were men. The men were sicker on admission, more likely to be smokers, and had at least one chronic health condition, such as cardiac disease or cancer. Severe sepsis occurred in 588 (31 percent) subjects. Of these, about half had severe sepsis on their first day of hospitalization.
The GenIMS researchers hope to identify whether certain changes in the genes for key inflammatory molecules are associated with the risk of developing pneumonia, and the risk of progression to severe sepsis, septic shock, organ dysfunction, or death. Because pneumonia is the most common cause of sepsis, patients with this infection represent an excellent clinical model for studying sepsis in a relatively homogeneous population.
GenIMS researchers led by Drs. Yende and Angus found that people with certain gene variations associated with higher levels of macrophage migration inhibitory factor, an innate immune response regulator, were less likely to die following CAP.
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McGowan Institute for Regenerative Medicine faculty member Savio L-Y. Woo, PhD, DSc, University Professor of Bioengineering and the Founder and Director of the Musculoskeletal Research Center, University of Pittsburgh, has been elected an Honorary Member of the European Federation of National Associations of Orthopaedic Sports Traumatology (EFOST). This prestigious honor is bestowed on an individual for exemplary efforts in support of international sports medicine. Dr. Woo is the only non-surgeon to receive such an honor from this federation of clinicians. He will be presented the “Mark of Honor” during the EFOST Meeting being held in Brussels, Germany, November 2010.
After the First World Congress Sports Traumatology which was held in Palma de Mallorca in May 1992, Dr. Hans Paessler from Germany and Dr. Jean Claude Imbert from France had the idea of founding a new organization in Europe dealing with sports traumatology based on the association of different nations. The idea was to create a Federation of National Sports Traumatology Societies and not a simple society of individual members, with the purpose of coordinating and improving knowledge of sports-related injuries. The mission of EFOST is to spread the idea of a common effort in the field of sports traumatology in Europe, coordinating the Societies, and creating new ones in countries with no such organizations.
Congratulations, Dr. Woo!
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McGowan Institute Director, Alan Russell, PhD, recently was a feature interview on the “Big Think” online forum. His conversation, “The World of Regenerative Medicine,” provided a timely update on regenerative medicine and its current and future impact on health-related issues.
“Regenerative medicine captures the body’s ability to heal itself and accelerates that to a clinically relevant time scale,” said Dr. Russell. “Within our body, we have many natural mechanisms which allow us to heal, but they just take place rather slowly and possibly not quickly enough to defeat a disease. If we can understand how the body communicates with itself at a very scientific and biologic basis, then we can learn to intervene in that discussion that the body is having and get it to steer a different course.”
Other questions addressed by Dr. Russell during the interview included:
• How can regenerative medicine revolutionize healthcare?
• Why did you decide to specialize in it?
• Can regenerative medicine aid in prevention?
• Can regenerative medicine cure cancer?
• Where is regenerative medicine going from here?
“Big Think” is a global online forum connecting people and ideas. Through an ever-expanding platform of knowledge content, including in-depth interviews with the world’s leading experts, “Big Think” is a vital hub for important information to help users function, and succeed, in a rapidly changing world.
McGowan Institute for Regenerative Medicine faculty member Bradley Keller, MD, professor of Pediatrics at the University of Pittsburgh School of Medicine, and Graduate Faculty, Cell Biology and Molecular Physiology, University of Pittsburgh, is the director of a team of medical professionals from Children’s Hospital of Pittsburgh of UPMC who travel to and from China providing medical assistance to children with treatable and survivable heart conditions in developing countries where the appropriate medical facilities, expertise, or resources do not exist. The services are funded by the Variety Children’s Lifeline Foundation. Through the Foundation, Dr. Keller’s team works with families and patients sponsored by the organization, the South East Asia Prayer Center (SEAPC) Touching Hearts in Tibet.
Begun in 1999 and officially launched in 2000, Touching Hearts in Tibet has brought many needed medical procedures to numerous children who have serious heart conditions. During these medical missions, Dr. Keller and his team are eager to share their knowledge with their medical colleagues in the correspondent country. A rich resource of medical knowledge and equipment remains in the developing country, and the mission creates an integrated cross-cultural medical team. In addition to Dr. Keller’s team of professionals, cardiologists from Japan, Venezuela, and China, have cooperated in Touching Hearts.
Variety Children's Lifeline was founded in 1982 with its primary focus on pediatric cardiac surgeries; it also provides medical care in the areas of pediatric neurosurgeries, cranial-facial procedures, neo-natal clinics, general clinics, pediatric rehabilitative medicine, and plastic surgeries for children.
Dr. Keller is a physician-scientist with extensive experience in the design, execution, and analysis of cardiovascular research related to cardiovascular developmental physiology and biomechanics. He is actively involved in the expansion of clinical care delivery to patients of all ages with congenital heart diseases.
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To take advantage of the 220 million users of Facebook, the McGowan Institute has established a Facebook site. The expectation is that the Institute’s presence on Facebook will increase the visibility of the mission, vision and accomplishments at the Institute. In the traditional format used at Facebook, if you, your family members, your staff or trainees are Facebook users, we welcome you/them to become a “fan” of the McGowan Institute on Facebook.
The Regenerative Medicine Podcasts remain a popular web destination. Informative and entertaining, this is the most recent interview:
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Regenerative Medicine Today #69
Regenerative Medicine Today welcomes Marie Csete, MD, PhD, Chief Scientific Officer of the California Institute of Regenerative Medicine (CIRM). Dr. Csete summarizes the mission and vision of CIRM, and offers her observations on the possible relative availability of different regenerative therapies. Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews. |
| Authors: | Santiago LY, Clavijo-Alvarez J, Brayfield C, Rubin JP, Marra KG |
| Title: | Delivery of adipose-derived precursor cells for peripheral nerve repair |
| Summary: | To test the hypothesis that the transplantation of adipose precursor cells (APCs) improves nerve regeneration and functional recovery, human APCs were transplanted into the lumen of a nerve guide in a 6-mm unilateral sciatic nerve defect in athymic rats. The three control groups for the study were biodegradable, polycaprolactone-based nerve conduit without APCs, autograft, and empty defect. Behavioral tests were performed every 3 weeks, and the sciatic functional index (SFI) was calculated based on measurements from the hindlimb prints. After 12 weeks, the nerve as well as right and left gastrocnemius muscles were removed and preserved for histological evaluation. Full regeneration of the sciatic nerve occurred on the rats that received the autograft, the guide, and the guide with APCs; no regeneration was observed on any of the rats in which the defect was left untreated (empty defect). APCs survived transplantation for up to 12 weeks in the injured peripheral nerve. No significant colocalization was observed between the immunostaining for glial fibrillary protein and anti-human lamin A/C, implying that the APCs did not differentiate into Schwann cells at the site of injury. In comparison with the rats with untreated defects, a decrease in muscle atrophy was observed on those rats that received the autograft and the guide with cells as indicated by the gastrocnemius muscle weight ratio and the muscle fiber ratio. Significant differences in SFI were observed 3 weeks postinjury between the rats in which the guide was left empty and those that received the guide with APCs; however, these differences were not observed at 12 weeks. The transplantation of APCs promoted the formation of a more robust nerve as evidenced by the results from the cross-sectional area of regenerated nerve, and the transplantation of APCs produced a decrease in muscle atrophy. |
| Source: | Cell Transplant. 2009;18(2):145-58 |
PI |
Steven Little, PhD |
Title |
Temporal Delivery of Growth Factors for Wound Healing Using Porous Hollow Fibers |
Description |
Our objective is to optimize wound healing through temporal delivery of growth factors using porous hollow fibers extending into a wound site. As an extension to the wound-cap technology (artificial capillary bed delivery system), these fibers can be made from materials that dissolve in the presence of a chemical or temperature-based trigger following the wound healing process. Because angiogenesis is, in many cases, one of the first steps towards wound healing, we propose to demonstrate enablement of this technology by mimicking the natural sequence of stimuli that directs angiogenesis. Our hypothesis is that sequential delivery of appropriate angiogenesis-promoting factors from our externally-regulated delivery system, as opposed to simultaneous delivery of multiple factors, will result in more mature and integrated neo-vasculature. |
Source |
PTEI via DOD |
Term |
April 1, 2009 – September 30, 2010 |
| Amount: | $91,667 |
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