by Laura Lane
The use of human tissue in the life sciences is hardly new. In 1951, a researcher at Johns Hopkins University created the first human cell line with samples taken from an unwitting cancer patient. Named HeLa cells, they went on to serve crucial roles in the development of the polio vaccine and in the study of many diseases.
These days, human tissue research is more important than ever. The biopharmaceutical industry is now increasingly looking to human cells and tissues as a way to improve clinical trial results.
Traditionally, drug discovery and development have relied heavily on animal-based tests to assess efficacy, toxicity, and other parameters for potential new drugs. “You’ve only got to look at the current success rate of the pharmaceutical industry to see the problem with that,” says Robert Coleman, a human tissue research consultant. “The introduction of safe and effective new drugs onto the market is way below target, and even some of those that do make it are subsequently found to exhibit use-limiting side effects or even frank toxicity in patients.”
Animal house of cards
Having worked in drug discovery at Glaxo for 30 years, Coleman has firsthand experience with the frequent shortcomings of animal-based assays and animal studies. He gradually came to realize that positive results could often be obtained simply through the careful choice of animal model. Whereas one compound could pass with flying colors in one test species, another species could spell failure for that same compound.
“Those who have reviewed objectively the predictive power of animal experiments, have shown them to be consistently unreliable,” Coleman says. “Logically, it makes more sense to evaluate drugs intended for humans in human-based tests.”
More and more, the cells and tissues themselves serve as the treatment. The burgeoning field of tissue engineering is creating bones, blood vessels, organs, and other bodily structures in answer to an assortment of maladies. In addition, researchers are extracting cells from patients to “bioengineer skin substitutes, aid wound healing, counteract chronic inflammation, treat burns and pressure ulcers, and improve postoperative healing,” according to a 2009 paper in the journal Wounds (1).
In the near future, physicians will be able to rely on human tissue engineering know-how to treat an even wider set of conditions, such as cancer, stroke, heart disease, blood disorders, autoimmune diseases, spinal cord injuries, eye disorders, and hearing loss.
Fortunately, the explosion of enthusiasm for employing human tissues corresponds with the necessary supportive technologies and services. This includes the incubators that replicate the warm, nurturing environment of the human body. Big, small, short, and wide, incubators come in various sizes with all sorts of bells and whistles.
For culturing human cells and tissues, maintaining an environment with a neutral pH is of optimal importance. Outside of the pH range of 7.4 to 7.6, the growth and health of samples can be compromised. Carbon dioxide (CO2) incubators address this by ensuring a constant 5% CO2 atmosphere.
“By having that, it controls the pH in the media at neutral pH like in the human body,” says Ron Breuer, business development manager at Binder Inc.
Many incubators, such as those at Binder, can also help modulate the amount of oxygen and nitrogen to mimic special conditions. For example, researchers who want to create a hypoxic environment can opt for Binder’s CB series of feature-rich incubators. These offer a control circuit that feeds oxygen and nitrogen, in addition to CO2, in measured doses in response to a zirconium oxide sensor.
The latest addition to the CB series is the CB 53, a compact version with 53 liters, or 1.9 cubic feet, of storage space. And, like the other two in the CB series, you have the option of purchasing hardware for stacking the units on top of each other. Not only does the miniature size save precious space in congested laboratories, Breuer says, but it can also help to keep patients’ cells segregated and safe.
“You can buy a bunch of small ones and dedicate an incubator to one patient,” he says, noting that the doors come with a lock. “You’re less likely to have problems with confusing cells.”
Thomas Patzenhauer, online marketing manager at Binder, points out that the compact size comes in handy for fertility clinics. One unit can house the samples from one couple, thus reducing the chance of mishap with the emotionally tied process of in vitro fertilization. Binder’s reliable method of temperature regulation and ensuring that every corner of the unit remains at 37 degrees Celsius provides clinic technicians with added confidence.
“Any influence to this [temperature] and the cells might die,” Patzenhauer says. “And that’s not good if you want to have a baby in those Petri dishes.”
Contamination by extraneous microbial agents will also prove disappointing. Bacteria, yeast, fungi, and viruses can deprive cell cultures of essential nutrients, change the culture’s pH, alter cell morphology, and induce changes on the genetic and chromosomal level, says Daniela Maurer, Binder’s scientific product manager.
Choosing an incubator that provides adequate sterilization to guard against contamination can prevent such potholes in the research process. In addition, international standards dictate that sterilization employ heat of certain temperatures. For example, during sterilization in Binder’s incubators, temperatures reach 180 degrees Celsius, which meets or surpasses every standard.
While sufficient temperatures are of utmost importance, other features of Binder incubators’ design also support the fight against contamination. The air-circulating fan is located in an outer chamber to prevent any contamination from spreading throughout the inner chamber, which contains the samples. A unique double basin at the bottom of the inner chamber collects all condensation, keeping the other surfaces dry and depriving contaminants of the water they need to thrive. In addition, the entire structure is constructed of “just one piece of stainless steel,” says Uwe Ross, executive vice president at Binder. That means no sharp corners, seams, or pockets where contamination can hide.
Procure or purchase
Choosing and handling incubators are only a small part of life science and biomedical projects. Acquiring human cells and tissues, as well as plasma and serum, can bring true trials and tribulations to the task at hand. Researchers must first locate and identify patients or other donors who may harbor specimens of certain diseases, genetic types and other parameters, and then surmount the hurdles of ethics boards, gaining permission, and transport.
That’s where companies like Asterand come into play. They navigate through all those challenges, freeing researchers to focus on the science. With the many companies that offer human cells and tissues, the selection offers a very comprehensive set of diseases, types, and variations. Some companies also will take orders for custom procurements if they don’t already offer specific specimens.
The format may dictate which company earns your business. In addition to frozen and formalin-fixed paraffin embedded (FFPE), the tissues can also come in various formats, such as a tissue array.
Asterand offers a format that includes the tumor and adjacent normal tissue from a single case that is sliced into two pieces. Part of the QuadSet™ biospecimen collection, one section is formalin-fixed and comes as an FFPE sample, while the other section is flash frozen. Each are sliced in half to present mirror image faces for study. Quad Set Plus™ comes with the patient’s serum and plasma in addition to the tissues. This format is especially well suited for biomarker discovery and validation studies.
“We have 10 board-certified pathologists who review all the samples to validate the tissue quality and the specimen diagnosis so it’s accurate for the client,” says Shannon Richey, director of marketing for Asterand.
Soon, the company will begin to provide longitudinal patient outcomes of up to five years, in addition to the clinical data already provided. The additional information will give researchers more insight as they study the patients’ tissues, Richey says. “At the end of the day, this is about accelerating the discovery of new treatments for patients. Scientists need to know a lot about disease, and human tissue research can help improve their understanding.”
1. Kazmi et al., “Autologous Cell Therapy: Current Treatments and Future Prospects”, Wounds, 21:9, Sept, 9, 2009.