Every day thousands of people of all agesare admitted to hospitals because of themalfunction of some vital organ. Becauseof a dearth of transplantable organs, many of thesepeople will die. In perhaps the most dramatic ex-ample, the American Heart Association reportsonly 2,300 of the 40,000 Americans who needed anew heart in 1997 got one. Lifesaving livers andkidneys likewise are scarce, as is skin for burn vic-tims and others with wounds that fail to heal. Itcan sometimes be easier to repair a damaged auto-mobile than the vehicle’s driver because the formermay be rebuilt using spare parts, a luxury that hu-man beings simply have not enjoyed.An exciting new strategy, however, is poised torevolutionize the treatment of patients who neednew vital structures: the creation of man-made tis-sues or organs, known as neo-organs. In one sce-nario, a tissue engineer injects or places a given mol-ecule, such as a growth factor, into a wound or anorgan that requires regeneration. These moleculescause the patient’s own cells to migrate into thewound site, turn into the right type of cell and re-generate the tissue. In the second, and more ambi-tious, procedure, the patient receives cells—either hisor her own or those of a donor—that have been har-vested previously and incorporated into three-di-mensional scaffolds of biodegradable polymers,such as those used to make dissolvable sutures. Theentire structure of cells and scaffolding is transplant-ed into the wound site, where the cells replicate, re-organize and form new tissue. At the same time, theartificial polymers break down, leaving only a com-pletely natural final product in the body—a neo-or-gan. The creation of neo-organs applies the basicknowledge gained in biology over the past fewdecades to the problems of tissue and organ recon-struction, just as advances in materials science makepossible entirely new types of architectural design.Science-fiction fans are often confronted withthe concept of tissue engineering. Various televi-sion programs and movies have pictured individu-al organs or whole people (or aliens) growingfrom a few isolated cells in a vat of some power-ful nutrient. Tissue engineering does not yet rivalthese fictional presentations, but a glimpse of thefuture has already arrived. The creation of tissuefor medical use is already a fact, to a limited ex-tent, in hospitals across the U.S. These ground-breaking applications in-volve fabricated skin, carti-lage, bone, ligament andtendon and make musings of“off-the-shelf” whole organsseem less than far-fetched.Indeed, evidence abounds that it is at least theo-retically possible to engineer large, complex or-gans such as livers, kidneys, breasts, bladders andintestines, all of which include many differentkinds of cells. The proof can be found in any ex-pectant mother’s womb, where a small group ofundifferentiated cells finds the way to develop intoa complex individual with multiple organs and tis-sues with vastly different properties and functions.Barring any unforeseen impediments, teasing outthe details of the process by which a liver becomesa liver, or a lung a lung, will eventually allow re-searchers to replicate that process. A Pinch of ProteinCells behave in predictable ways when exposedto particular biochemical factors. In the simplertechnique for growing new tissue, the engineer ex-poses a wound or damaged organ to factors that actas proponents of healing or regeneration. This con-cept is based on two key observations, in bones andin blood vessels.In 1965 Marshall R. Urist of the University ofCalifornia at Los Angeles demonstrated that new,Growing New OrgansResearchers have taken the first steps toward creatingsemisynthetic, living organs that can be used as human replacement partsby David J. Mooney and Antonios G. MikosIt is theoretically possible to engineer organssuch as livers, kidneys, breasts and intestines.60 Scientific American April 1999GROWING NEWSPECIAL REPORTCopyright 1999 Scientific American, Inc.bony tissue would form in animals that receivedimplants of powdered bone. His observation ledto the isolation of the specific proteins (the bonemorphogenetic proteins, or BMPs) responsiblefor this activity and the determination of theDNA sequences of the relevant genes. A numberof companies subsequently began to producelarge quantities of recombinant human BMPs;the genes coding for BMPs were inserted intomammalian cell lines that then produced theproteins. Various clinical trials are under way to test theability of these bone growth promoters to regen-erate bony tissue. Applications of this approachthat are currently being tested include healingacute bone fractures caused by accidents andboosting the regeneration of diseased periodon-tal tissues. Creative BioMolecules in Hopkinton,Mass., recently completed clinical trials showingthat BMP-7 does indeed help heal severe bonefractures. This trial followed 122 patients withleg fractures in which the sections failed to rejoinafter nine months. Patients whose healing wasencouraged by BMP-7 did as well as those whoreceived a surgical graft of bone harvested fromanother part of their body.A critical challenge in engineering neo-organsis feeding every cell. Tissues more than a few mil-limeters thick require blood vessels to grow intothem and supply nutrients. Fortunately, investi-gations by Judah Folkman have shown that cellsalready in the body can be coaxed into produc-ing new blood vessels. Folkman, a cancer re-searcher at Harvard Medical School’s Children’sHospital, recognized this possibility almost threedecades ago in studies aimed, ironically, at theprevention of cellular growth in the form of can-cerous tumors. Folkman perceived that developing tumorsneed to grow their own blood vessels to supplythemselves with nutrients. In 1972 he proposedthat specific molecules could be used to inhibitsuch vessel growth, or angiogenesis, and per-haps starve tumors. (This avenue of attackagainst cancer became a major news story in1998.) Realizing that other molecules wouldundoubtedly abet angiogenesis, he and othersGrowing New OrgansHuman body may be more than a sum of parts, but re-placing failing parts should extend and improve life.ORGANSGRANT JERDINGCopyright 1999 Scientific American, Inc.have subsequently identified a number of factors ineach category.That work is now being exploited by tissue engi-neers. Many angiogenesis-stimulating molecules arecommercially available in recombinant form, andanimal
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