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BREAKTHROUGHS in BIOSCIENCE/ ADVISORY COMMITTEE REGENERATIVE MEDICINE CHAIR» AUTHOR» Paula H / FALL 2016 Regenerative Medicine Advances from the Convergence of Biology & Engineering WHAT'S INSIDE » EXCEPTIONAL REGENERATION IN NATURE 2 / NATURAL REGENERATION IN HUMAN TISSUES 3 TISSUE ENGINEERING 4 / CONSTRUCTING SKIN 7 / TUBULAR ORGANS 8 / BONE ENGINEERING 8 MENDING BROKEN HEARTS 8 / REAWAKENING THE HUMAN HEART 10 / THE ROAD AHEAD 11 BREAKTHROUGHS IN BIOSCIENCE/ ADVISORY COMMITTEE REGENERATIVE MEDICINE CHAIR» AUTHOR» Paula H. Stern, PhD Cathryn M. Delude, of Santa Fe, New Mexico, writes about Northwestern University Feinberg School of Medicine science and medicine for magazines, newspapers, and COMMITTEE MEMBERS» research institutes. Her articles have appeared in Nature Aditi Bhargava, PhD Outlook, The Journal of the National Cancer Association University of California, San Francisco (JNCI), AACR’s Cancer Discovery, Proto: Dispatches from David L. Brautigan, PhD the Frontiers of Medicine, Los Angeles Times, Boston Globe, University of Virginia School of Medicine New York Times, Scientific American, and The Scientist. She has also written for the Howard Hughes Medical Institute, David B. Burr, PhD Harvard Health Publications, Harvard School of Public Health, Indiana University School of Medicine Massachusetts General Hospital, Massachusetts Institute of Blanche Capel, PhD Technology, Dana Farber Cancer Center, Stowers Institute Duke University Medical Center for Medical Research, and the National Institutes of Health Rao L. Divi, PhD Office of Science Education. This is her fifth article in FASEB’s National Cancer Institute, National Institutes of Health Breakthroughs in Bioscience series. Marnie Halpern, PhD SCIENTIFIC ADVISOR» Carnegie Institution for Science Henry J. Donahue, PhD is the School of Engineering Foun- dation Professor and Chair of the Department of Biomedical Loraine Oman-Ganes, MD, FRCP(C), CCMG, FACMG Engineering at the Virginia Commonwealth University. He Sun Life Financial received his PhD in Biology from the University of California, Sharma S. Prabhakar, MD, MBA, FACP Santa Barbara and completed a post-doctoral fellowship at Texas Tech University Health Sciences Center the Mayo Clinic. He has over 25 years of experience studying R. Brooks Robey, MD, FASN, FAHA musculoskeletal biology, using both in vitro and in vivo mod- White River Junction VA Medical Center and els. His research focuses on understanding the mechanism by Geisel School of Medicine at Dartmouth which bone and muscle adapt to their mechanical environ- ment; examining the effects of space flight on musculoskeletal Scott I. Simon, PhD tissues; and exploiting biophysical signals, including shear University of California, Davis stress and nanotopography, to develop innovative strategies to regenerate musculoskeletal tissue lost to disease, injury, or aging. His research has been continually funded by the FASEB MANAGING EDITOR National Institutes of Health for nearly 25 years, and he has Anne M. Deschamps, PhD also had funding from the Department of Defense, NASA/Na- Senior Science Policy Analyst tional Space Biology Research Institute, private foundations, FASEB Office of Public Affairs and industry. SCIENTIFIC REVIEWER» Thomas A. Stewart, PhD The Breakthroughs in Bioscience series is a collection of Yale University illustrated articles that explain recent developments in basic biomedical research and how they are important to society. Electronic versions of the articles are available in html and ON THE COVER» pdf format at the Breakthroughs in Bioscience website: The image, which was a winner in the 2012 FASEB BioArt www.faseb.org/breakthroughs Competition, shows a three-dimensionally woven biomaterial FOR REPRINTS OR OTHER INFORMATION» scaffold. Multiple layers of resorbable fiber bundles have been Federation of American Societies for Experimental Biology woven into a porous structure. The scaffold is then seeded Office of Public Affairs with cells that grow to become new tissue as the fibers are 9650 Rockville Pike resorbed. Farshid Guilak, PhD, (Washington University in St. Bethesda, MD 20814-3998 Louis and Cytex Therapeutics, Inc.) and Frank Moutos, PhD, (Cytex Therapeutics, Inc.) developed this scaffold in hopes of © Copyright 2016, FASEB, All rights reserved. growing replacement cartilage to resurface joints. Regenerative Medicine Advances from the Convergence of Biology & Engineering THROUGHOUT HISTORY, WE HAVE DREAMED of healing untreatable STEM CELL FACTORIES » Spherical microcarriers wounds, replacing a disfiguring scar with healthy skin, growing replacement lungs in the (blue) aid in the growth of laboratory, reawakening the body’s dormant ability to regenerate, and replacing a leg lost adult stem cells (green) that have been isolated from to injury or disease. Those are, in fact, the ultimate goals of the interdisciplinary field called skeletal muscle. Douglas regenerative medicine. Cowan at Boston Children’s Hospital is applying this Dreams of regeneration took shape in ancient myths and also after minor injuries. Unfortunately, most of our technology in hopes of cre- and legends. Greek mythology told of how the god Pro- organs and tissues have only limited abilities to repair ating microscopic stem cell factories. Image credit: 2012 metheus, chained to a rock, regrew his liver overnight themselves and restore lost function. Instead, we re- FASEB BioArt Competition after an eagle pecked at it each day. quire prosthetics or organ transplants when we have lost or injured essential body parts. What is fascinating is that the human liver can actually regenerate itself from just a small portion—as little as The abilities of the human liver, skin, and bone to regen- a quarter of its original size. Skin and bone can also erate pale in comparison to some members of the animal partially regenerate themselves as part of daily living kingdom. Great thinkers from Aristotle and Voltaire to 1 REGENERATIVE MEDICINE » ADVANCES FROM THE CONVERGENCE OF BIOLOGY & ENGINEERING Charles Darwin and Thomas Hunt Morgan, the “father of WORDS, DEMYSTIFIED genetics,” marveled at enviable examples of regeneration DIFFERENTIATED: Mature in other animal species (Figure 1). For example, salaman- cells that have a special- ders and sea stars can perfectly regenerate lost limbs and ized structure or function arms. Zebrafish can replace lost fins to exact proportions, UNDIFFERENTIATED: and a family of flatworms called planaria can completely Immature cells that lack restore their entire body from a tiny segment. Scientists specialized structure or continue to uncover the biological principles that underlie function; can give rise these animals’ regenerative abilities in hopes of learning to specialized cells how to stimulate regeneration in humans. DE-DIFFERENTIATE: In general, regenerative medicine utilizes two approach- To lose the structure es: (1) reawakening the body’s own dormant ability to FIGURE 1 / ANIMAL MODELS OF REGENERATION and function of special- » renew and repair tissues from within, or (2) growing re- Zebrafish, salamander (axolotl), sea star, and planarian. Image ized cells and revert to placement tissues in the laboratory to implant in the body, credits: Azul via Wikimedia Commons (zebrafish); LoKiLeCh an earlier, immature via Wikimedia Commons (salamander); Nick Hobgood via Wi- an area called tissue engineering. Some tissue engineer- developmental state kimedia Commons (Sea star); Holger Brandl, HongKee Moon, ing applications, such as those for skin and cartilage, Miquel Vila-Farré, Shang-Yun Liu, Ian Henry, and Jochen C. STEM CELL: An undif- already have US Food and Drug Administration (FDA) Rink via Wikimedia Commons (planaria) ferentiated cell that approval for clinical use. Others, including tissue-engi- can self-renew and also give rise to multiple neered bladders and trachea (windpipe) are in pilot stud- Scientists also observed a similar mass of rapidly divid- specialized cell types ies in humans, and many more are being evaluated in laboratory animals in preparation for human studies. ing cells form when they amputated a fin in bony fish. PROGENITOR: A partially Within a week, a new fin emerged with the proper size, differentiated cell that has In the past twenty years, rapid advances in medicine shape, and orientation. Likewise, salamanders and more limited self-renew- and surgery, developmental and stem cell biology, newts regenerated perfectly formed tails and limbs af- al and differentiation biochemistry and bioengineering, and the material ter amputation. A young larva reproduced small limbs; potential than stem cells and physical sciences have propelled the field for- an adult regrew full-sized ones. PROLIFERATE: To multiply ward, thanks largely to key funding from the National Institutes of Health (NIH), National Science Founda- Researchers have wondered whether the cells involved tion (NSF), the Department of Defense (DOD), and in the regeneration of missing structures come from ex- the Armed Forces Institute for Regenerative Medicine isting populations of naïve, undifferentiated cells (e.g., (AFIRM). Almost every week, researchers report new stem cells) that are maintained in the body or if they successes in the laboratory, fueling optimism that we arise by de-differentiation of remaining cells. Until re- may indeed attain the age-old dream of regeneration, cently, researchers could not answer that question be- at least for some of our tissues. cause they had no way to track where dividing cells came from and where they ended up. EXCEPTIONAL REGENERATION IN NATURE New genetic and cell imaging techniques developed
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