NEWS FEATURE to personally pick up the samples from the sur- Tracking down tissues geons’ offices, eventually building a network of more than 18 surgeons who contribute an aver- FDA inspections of tissue banks remain a work in progress, and no age of 50 liters of fat per month from consenting patients. Using that tissue, Cytori developed an clear path yet exists for procuring human tissues for biomedicine or automated system that separates stem and other drug development. Emily Waltz investigates. regenerative cells from the fat, and the company is now developing cell-based therapies that treat cardiovascular disease and aid healing in recon- Last year’s headlines about an underground structive breast surgery. trade in human body parts in New Jersey1 Cytori researchers are not alone in concocting prompted a public outcry and the formation a patchwork method for gleaning human tissue. of the Human Tissue Task Force (HTTF)—an Companies frequently approach clinical col- internal US Food and Drug Administration leagues, body donation programs, tissue banks, (FDA) body with the specific mission of tight- for-profit brokers and even their own employees ening the oversight of human tissue procure- to get samples for drug studies. Obtaining tissue ment. This summer, the HTTF released its using these methods is usually legal and ethi- first report, which identified several areas in cal, say experts, as long as the proper consent is need of improvement, such as tracking systems obtained and the tissues themselves are not sold and more regular audits2. Two months later, for a profit. FDA inspections of a few hundred (of several Some of the most frequently studied tissues thousand) human tissue banking and procur- are biopsies and tumors from living donors. ing facilities revealed that the number of estab- Like many companies, Bristol-Myers Squibb, http://www.nature.com/naturebiotechnology lishments with ‘objectionable conditions’ had based in Princeton, New Jersey, collects tissue more than doubled (http://www.fda.gov/cber/ samples from consenting cancer patients in its tissue/inspdata.htm). Although according to the clinical trials to look for molecular corollaries FDA these situations pose little risk to human and potential targets. health, companies requiring human tissue for To help cut down on surprises when a com- R&D still face a mélange of options in a supply pound goes from animal models to the clinic, system that is disorganized and scattered. And as companies sometimes use human tissue as an the demand for human tissue grows, companies Inc. Researchers, AJPhoto/Photo additional preclinical step. “We do a lot of weed- are having to find their own ways of collecting In the US, the demand for human tissues for drug ing out in that process,” says Mark Cockett, vice material and determining its quality. R&D is growing. president of applied genomics at Bristol-Myers. “There have been a number of programs that Nature Publishing Group Group Nature Publishing 7 Big demand we have stopped working on because we discov- The HTTF was set up last year by the FDA after back to the question: What is the best material to ered that the human biology is different than the 200 © it discovered that a New Jersey tissue recov- use? Time and time again, the answer is human mouse biology.” ery company and several funeral homes were tissue,” he says. “This industry has spent billions “Using human cells allows an early read stealing body parts from the deceased, forging of dollars trying to duplicate what already exists on safety,” adds Neil Warma, CEO of Viron medical records and passing the tissues on to [in nature].” Therapeutics in London, Canada. “It gives hospitals for transplant. The FDA closed down Yet in the United States, there is no central you the advantage of stopping development the company and the principals were indicted. clearinghouse or resource center for these tis- early, and the cost savings associated with that Experts say this kind of egregious abuse is sues. Instead, tissue providers have popped up are enormous.” Viron is developing viral pro- driven largely by the great demand from the all over the country to meet clinical needs, scat- tein–based anti-inflammatory therapeutics medical community for donated human tis- tering the tissue supply. A mishmash of US state and often demonstrates efficacy using human sue—a demand that has increased rapidly over and federal oversight hasn’t helped organize the tissues, such as endothelial cells and hepato- the past two decades. As drug discovery becomes system and, at the same time, has allowed some cytes, that are configured into customized cell- increasingly target driven, scientists are finding nefarious characters peddling dirty body parts interaction assays. more applications for human tissue. Nearly to succeed in the industry. Scientists, especially Hepatocytes, isolated from whole donated liv- any scientist who tests drug candidates, har- those looking for specific or unusual tissue, are ers and liver resections, are a frequent request vests regenerative cells, makes delivery devices often forced to find their own way. from scientists who study toxicology and drug– or creates bioimplants will likely have a use for drug interaction of compounds. The cells, which donated human tissues. Do-it-yourself networks act as a filter through which drugs must pass and But with the unpredictability of death and When the founders of San Diego–based Cytori do a majority of the detoxification and metab- the reluctance of the public to donate, there Therapeutics realized in 2004 that they needed olism in the body, are important indicators of often isn’t enough tissue to go around. “If sup- enormous amounts of human fat to develop whether a drug might change or become inac- ply wasn’t a problem, human tissue would be their technologies, they began collecting it the tive. The FDA requires metabolism and toxicol- used in every procedure out there,” says Jamie best way they knew how: they called the plastic ogy data for every new drug before it is approved Grooms, CEO of AxoGen in Alachua, Florida. surgeons in their address books and asked them and sometimes specifically recommends that a The firm is developing peripheral nerve grafts to save the fat from their patients’ liposuction company test its candidate on human tissue from donated nerve tissue. “It always comes procedures. The company sent its employees before it reaches clinical stages. 1204 VOLUME 25 NUMBER 11 NOVEMBER 2007 NATURE BIOTECHNOLOGY NEWS FEATURE clearinghouse for research tissue. It keeps an Table 1 Selected vendors of human whole tissues and cells inventory of frozen samples of everything from Institute/Company Tissues arteries to uteri and also places fresh tissue National Disease Research Frozen tissue inventory and fresh tissue liaison; big selection, directly with researchers. Interchange (NDRI) including rare diseases, HIV, cord blood, stem cells, tissue microar- rays, pancreatic islets, arteries and whole organs Nonorgan tissue destined for implantation International Institute for the Fresh tissue liaison; frozen tissue inventory; whole body donation is sent to processing companies that special- Advancement of Medicine (IIAM) program; normal and diseased tissue; whole organs ize in cleaning and shaping it. Allosource, of (Jessup, Pennsylvania) Centennial, Colorado, specializes in musculo- Lonza Walkersville Isolated cells from fresh, normal tissue; inventory of frozen cells; skeletal tissue and sells everything from patella custom procurement of non-normal tissue wedges to Achilles tendons. They obtain the tis- AllCells (Emeryville, California) Primary cells from normal and diseased tissue, including sue through four large OPOs, screen it for dis- hematopoietic, endothelial, leukemia and dendritic cells eases, eradicate bacteria and then cut and shape Asterand (Detroit, Michigan) Fresh, frozen and formalin-fixed paraffin-embedded samples; it. Tissue distributors, such as Medtronic’s spinal primary cells; tissue microarrays; custom procurement division in Memphis, Tennessee, often connect processing companies with implant surgeons. Other companies specialize in isolating cells In addition, a host of firms incorporate Sharing (UNOS; http://www.unos.org) to find from donated tissues. Lonza Corporation has human tissue into implant products and regen- a recipient and helps coordinate the transfer of a division called Lonza Walkersville, based erative therapies. For example, Organogenesis, the organ. In 2006, nearly 15,000 people donated in Walkersville, Maryland, that specializes in based in Canton, Massachusetts, makes a cir- an organ, but at any given time nearly 100,000 this area and will set up customized donation cular piece of bioengineered skin the size of a people are awaiting an organ transplant, accord- programs to meet specific requests. Columbia, hockey puck that integrates into wounds, such ing to statistics kept by UNOS. Maryland–based Osiris Therapeutics goes to as venous leg ulcers, and helps them heal. The Viable organs, particularly the kidneys, liver, Lonza for bone marrow. Osiris is developing http://www.nature.com/naturebiotechnology bilayered product is made by incorporating heart, lungs and pancreas, get priority over therapies using mesenchymal cells separated collagen with fibroblasts and keratinocytes research needs when there is a potential recipi- from bone marrow for graft-versus-host disease, from newborns’ circumcised foreskin, which ent waiting for a transplant. For organs that Crohn’s disease, acute myocardial infarction and the company gets from local hospitals where cannot be used for transplantation, some OPOs, arthritis of the knee. parents have consented to donate, according to such as the New York Organ Donor Network, Living donations—such as biopsies, amni- Geoff MacKay, Organogenesis’ CEO. Now that in New York City, have established relationships otic fluid and tumors—that would other- they’ve honed their technique, they can make with researchers and connect them directly with wise be disposed of as hazardous waste, are about 100,000 final products from one piece of the fresh tissue. fairly plentiful and more likely to end up with discarded foreskin.