SPECIAL REPORT GROWING NEW Researchers have taken the first steps toward creating semisynthetic living organs that can be used as human replacement parts by David J Mooney and Antonios G Mikos E very day thousands of people of all ages are admitted to hospitals because of the malfunction of some vital organ Because of a dearth of transplantable organs many of these people will die In perhaps the most dramatic example the American Heart Association reports only 2 300 of the 40 000 Americans who needed a new heart in 1997 got one Lifesaving livers and kidneys likewise are scarce as is skin for burn victims and others with wounds that fail to heal It can sometimes be easier to repair a damaged automobile than the vehicle s driver because the former struction just as advances in materials science make possible entirely new types of architectural design Science fiction fans are often confronted with the concept of tissue engineering Various television programs and movies have pictured individual organs or whole people or aliens growing from a few isolated cells in a vat of some powerful nutrient Tissue engineering does not yet rival these fictional presentations but a glimpse of the future has already arrived The creation of tissue for medical use is already a fact to a limited extent in hospitals across the U S These groundbreaking applications involve fabricated skin cartilage bone ligament and tendon and make musings of off the shelf whole organs seem less than far fetched Indeed evidence abounds that it is at least theoretically possible to engineer large complex organs such as livers kidneys breasts bladders and intestines all of which include many different kinds of cells The proof can be found in any expectant mother s womb where a small group of undifferentiated cells finds the way to develop into a complex individual with multiple organs and tissues with vastly different properties and functions Barring any unforeseen impediments teasing out the details of the process by which a liver becomes a liver or a lung a lung will eventually allow researchers to replicate that process It is theoretically possible to engineer organs such as livers kidneys breasts and intestines may be rebuilt using spare parts a luxury that human beings simply have not enjoyed An exciting new strategy however is poised to revolutionize the treatment of patients who need new vital structures the creation of man made tissues or organs known as neo organs In one scenario a tissue engineer injects or places a given molecule such as a growth factor into a wound or an organ that requires regeneration These molecules cause the patient s own cells to migrate into the wound site turn into the right type of cell and regenerate the tissue In the second and more ambitious procedure the patient receives cells either his or her own or those of a donor that have been harvested previously and incorporated into three dimensional scaffolds of biodegradable polymers such as those used to make dissolvable sutures The entire structure of cells and scaffolding is transplanted into the wound site where the cells replicate reorganize and form new tissue At the same time the artificial polymers break down leaving only a completely natural final product in the body a neo organ The creation of neo organs applies the basic knowledge gained in biology over the past few decades to the problems of tissue and organ recon60 Scientific American A Pinch of Protein C ells behave in predictable ways when exposed to particular biochemical factors In the simpler technique for growing new tissue the engineer exposes a wound or damaged organ to factors that act as proponents of healing or regeneration This concept is based on two key observations in bones and in blood vessels In 1965 Marshall R Urist of the University of California at Los Angeles demonstrated that new Growing New Organs April 1999 Copyright 1999 Scientific American Inc bony tissue would form in animals that received implants of powdered bone His observation led to the isolation of the specific proteins the bone morphogenetic proteins or BMPs responsible for this activity and the determination of the DNA sequences of the relevant genes A number of companies subsequently began to produce large quantities of recombinant human BMPs the genes coding for BMPs were inserted into mammalian cell lines that then produced the proteins Various clinical trials are under way to test the ability of these bone growth promoters to regenerate bony tissue Applications of this approach that are currently being tested include healing acute bone fractures caused by accidents and boosting the regeneration of diseased periodontal tissues Creative BioMolecules in Hopkinton Mass recently completed clinical trials showing that BMP 7 does indeed help heal severe bone fractures This trial followed 122 patients with leg fractures in which the sections failed to rejoin after nine months Patients whose healing was encouraged by BMP 7 did as well as those who received a surgical graft of bone harvested from another part of their body A critical challenge in engineering neo organs is feeding every cell Tissues more than a few millimeters thick require blood vessels to grow into them and supply nutrients Fortunately investigations by Judah Folkman have shown that cells already in the body can be coaxed into producing new blood vessels Folkman a cancer researcher at Harvard Medical School s Children s Hospital recognized this possibility almost three decades ago in studies aimed ironically at the prevention of cellular growth in the form of cancerous tumors Folkman perceived that developing tumors need to grow their own blood vessels to supply themselves with nutrients In 1972 he proposed that specific molecules could be used to inhibit such vessel growth or angiogenesis and perhaps starve tumors This avenue of attack against cancer became a major news story in 1998 Realizing that other molecules would undoubtedly abet angiogenesis he and others GRANT JERDING ORGANS Human body may be more than a sum of parts but replacing failing parts should extend and improve life Growing New Organs Copyright 1999 Scientific American Inc PRASAD SHASTRI AND IVAN MARTIN Massachusetts Institute of Technology have subsequently identified a number of factors in each category That work is now being exploited by tissue engineers Many angiogenesis stimulating molecules are commercially available in recombinant form and animal
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