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Cell and Tissue Engineering

Tissue engineering research aims to develop artificial tissues from natural materials using genetically modified cells and matrices. It also seeks to develop uses for artificial biopolymers, both degradable and nondegradable, to improve tissue and organ function. It is an integrated approach that utilizes engineering and biomaterial sciences, biochemistry, and cell and molecular biology.

Tissue Engineering research is conducted by faculty of the Department of Bioengineering and the Institute for Medicine and Engineering. The underpinnings of the future of this field are likely to be in stem cell biology/technology, molecular biology, and genomics. Dependable matrices to aid in the delivery of natural materials will continue to play an important role. Stem cell research in various areas takes place at the School of Medicine. Pioneering work is conducted at Penn's Center for Neurodegenerative Disease Research (CNDR), where investigators study the use of human embryonal cells as neuron grafts for cell therapy in stroke, and as a platform for the delivery of gene therapy for other brain diseases. Extensive gene therapy research is conducted in Penn's Institute for Human Gene Therapy (IHGT), and the use of biopolymeric matrices is studied by several investigators at the Laboratory for Research on the Structure of Matter (LRSM) and the Institute for Medicine and Engineering (IME).

Transplantation Of Human Neurons To Treat Brain Diseases at Penn's Center For Neurodegenerative Disease Research

The mission of Penn's Center for Neurodegenerative Disease Research (CNDR) is to conduct multidisciplinary clinical and basic research studies that increase understanding of the causes and mechanisms leading to brain dysfunction and degeneration in Alzheimer's disease, Parkinson's disease, motor neuron disease and other less common neurodegenerative disorders that also occur more frequently with advancing age.

CNDR was founded in 1991 and was awarded a grant from the National Institute on Aging of the National Institutes of Health (NIH) to establish the first and only NIH-funded Alzheimer Disease Center in the Delaware Valley, part of a network of 27 cooperating NIH-funded Centers throughout the nation. John Q. Trojanowski M.D., Ph.D., and Virginia M.-Y. Lee, Ph.D. established and are co-directors of CNDR. Together, they lead a team of over 35 University of Pennsylvania researchers, including Penn undergraduates, School of Medicine graduate students, postdoctoral fellows, technicians, and research associates. CNDR researchers and their network of collaborators within and outside Penn work on a variety of projects that are funded by several NIH and foundation grants to CNDR. The Center is housed in a state-of-the-art suite of laboratories contained within 6,500 square feet of research space on the third floor of Maloney Building in the heart of the Penn campus. However, the Center also functions as a "virtual center without walls" where University of Pennsylvania investigators and collaborators at other institutions converge to conduct multidisciplinary research studies of in Alzheimer's disease, Parkinson's disease, and related neurodegenerative diseases of aging. Given the mission of the Center to facilitate the development of better diagnostic strategies and effective new therapies of these disorders, CNDR encourages the rapid translation of progress at the lab bench to the bedside. Accordingly, Center researchers pursue a comprehensive array of research activities that extend from studies in test-tubes or cell-culture systems to those involving animal models of neurodegenerative diseases as well as to patient-based clinical and basic research studies.

Transplantation Of Human Neurons To Treat Brain Diseases:

CNDR investigators have characterized a human embryonal carcinoma cell line (NTera-2 or NT2 cells) that is transfectable and capable of differentiating into post-mitotic neuron-like cells (NT2N cells) following treatment with retinoic acid in order to identify a human neuronal cell line that might serve as a "platform" for gene therapy or for use as cell therapy for human neurological diseases. Studies of NT2N cells transplanted into the brain or spinal cord of immune competent and immunodeficient rodents show that NT2N cells integrate into the host central nervous system (CNS), and establish the molecular and structural polarity of authentic neurons in vivo. Further, grafted NT2N cells acquire the molecular phenotype of fully mature neurons within 6 months post-implantation and the grafts survive 1 year in immunodeficient mice without reverting to a neoplastic state. Following the demonstration in a rodent model of ischemic stroke that grafted NT2N neurons ameliorated motor and cognitive impairments in this animal model, an FDA approved clinical trial of the use of NT2N grafts to treat stroke patients was initiated in 1998 by investigators at the University of Pittsburgh, and the Phase 1 stage of the trial was completed successfully as reported by Kondziolka et al. in the journal NEUROLOGY (55:565-569, 2000). Based on these and related studies, the Phase 2 clinical trial of NT2N grafts for stroke will begin soon, and current data suggest it is plausible that grafted NT2N cells could serve as a suitable "platform" for the delivery of exogenous proteins into the CNS for gene therapy of human nervous system diseases or for use as cell therapy for these disorders.

For more information on Penn's Center for Neurodegenerative Disease Research, please visit http://www.med.upenn.edu/cndr

For more information on Penn's Department of Bioengineering, please visit http://www.seas.upenn.edu/be/index.html

For more information on Penn's Institute for Human Gene Therapy, please visit http://www.med.upenn.edu/ihgt/

For more information on Penn's Institute for Medicine and Engineering, please visit http://www.med.upenn.edu/ime/

For more information on Penn's Laboratory for Research on the Structure of Matter, please visit http://www.lrsm.upenn.edu

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Biological Engineering Network at the University of Pennsylvania
1010 Vagelos Research Labs / 3340 Smith Walk / Philadelphia PA 19104-6383
tel. 215-573-6813 ~ fax. 215-573-6815 ~ e-mail: ben-penn@pobox.upenn.edu