The Importance of Human Tissue Samples and Bio-Fluid Biospecimens in Cancer Research

Medical research on cancer and other diseases requires access to unique tools and materials, including human biospecimens and biofluids to study. Since most biological materials are both fragile and perishable, special care must be taken to be certain that they are processed and preserved properly to ensure viability. 

Fresh human tissue biospecimens and biofluids are best for modeling living tissue in the human body. For scientists and researchers, fresh tissue provides a platform for early-stage immunotherapy development. Additionally, individual tumor cells (either primary or dissociated) allow for the characterization of tumors and the exploration of important molecular and cellular pathways.

Usually there are two major tissue preparation methods used, FFPEs and fresh frozen tissue samples.

For a long time, human tissues have been processed as FFPE tissue blocks, also known as formalin-fixed paraffin-embedded. These are human tissue samples which have been saturated with formalin and then embedded in a block of paraffin wax (referred to as formalin-fixed paraffin-embedded or FFPE tissue).

With the invention of reliable ultra-low temperature freezers and ample availability of liquid nitrogen, it has become feasible to freeze tissue as a second means of long-term storage.

The Importance of Human Tissue Samples and Bio-Fluid Biospecimens in Cancer Research

Fresh Frozen Tissue Samples

Frozen tissue refers to tissue samples that has been rapidly frozen, typically using liquid nitrogen, for preservation and analysis. This process is crucial for preserving the structural integrity and biochemical components of the tissue, allowing for various microscopic and molecular studies.

Human tissue degrades quickly at room temperature and does not store well when kept in a standard “-20” food or household freezer. You must freeze the tissue samples as soon as possible, and then keep it very cold.

Frozen tissues are used for molecular genetic analysis – especially if the biopsy materials are dipped in liquid nitrogen in a method called “flash freezing,” and then stored in an ultra-cold freezer at less than -80 degrees Celsius.  A dedicated ultra-low temperature freezer is required to keep the human tissue samples always frozen.

Collection and Processing of Fresh Frozen Tissue Samples

Fresh tissue biospecimens are mainly used to isolate a unique cell type or prepare a smaller 3D structure. Therefore, the human tissue needs to be carefully collected within the appropriate culture media and processed within the appropriate time and temperature perimeters.

Cell isolation from tissue samples requires subsequent digestion or disintegration steps. This process must be carefully undertaken following special protocols and lab conditions. The digestion approach, mechanical or enzymatic, will be dictated by the type of tissue. The protocol should also consider the desired cell type as the conditions will differ.

Although no digestion or fragmentation is necessary when working with blood samples, isolating fresh and functional blood cells comes with more requirements and specifications than the classic buffy coat isolation.

FFPE Tissue Samples

Formalin-fixed paraffin-embedded tissues are the most common sources of archived material. Pathologists at hospitals have been creating and archiving FFPE tissues for decades.

Whenever they study a biopsy taken from a patient, they archive some of this material for later use – sometimes referring to it, or gaining second opinions, during a patient’s course of treatment. Researchers have also preserved donated tissues from humans, or materials collected from animals, to create archives of materials for later study. These archives are called “biobanks” and can be developed by universities and hospitals or created for commercial purposes by companies that serve the research community.

Since these archival materials have been created over a very long time, they can offer a historical perspective, as well as simply being a plentiful source of research material.

FFPE tissue blocks can be stored in a cabinet at room temperature, it is cheap to create a large collection that will be stable for a very long time. The formalin and wax preserve fragile structures inside and between the cells in the tissue – which makes FFPE tissue great for folks looking at cell and tissue morphology – such as pathologists who study preserved biopsies to diagnose cancer. The proteins in FFPE tissue are also preserved, not just the structures visible under a microscope.

Histologists can use fluorescently labeled antibodies (or antibodies tagged by other means) that specifically bind to certain proteins to see if they are present in certain cells within tissues, and if the locations and amounts of these proteins are different in diseased vs healthy tissues. This method is referred to as immunohistochemistry (IHC). Lastly, since FFPE is an old and well-established method for tissue storage, pathologists are accustomed to examining, and making diagnoses from, FFPE tissue biopsies.

Fresh Frozen Tissue Samples Vs FFPE Tissue Samples

Frozen tissue preserves the DNA, RNA, and native proteins. However, frozen tissue archives can be quickly lost due to power outages, mechanical failure, or carelessness in the lab. Frozen tissues are also less familiar to pathologists, who are generally more comfortable making diagnoses after microscopic analysis of FFPE tissue.

FFPE tissues are well-suited to creating large archives of tissues for research. Once prepared, FFPE tissue is very robust. It does not need special equipment to keep it stable for decades.

Pathologists have been making diagnoses from FFPE tissue for decades and are very familiar with it. FFPE tissue can also be used for some IHC studies. FFPE tissue samples may not be suitable for analysis native proteins and generally is inferior for the types of genetic analysis, such as PCR, qPCR, or next generation DNA sequencing, that are becoming commonplace.

Human Bio-Fluids

Human biofluids are biological liquids within an organism’s body, including fluids like whole blood, lymph, and interstitial fluid. They play a crucial role in transporting nutrients, removing waste, and maintaining the body’s overall health. Biofluids can also be examined for diagnostic purposes.

A human biofluid is a water-based liquid that contains solutes essential to body functions, thus makes highly variable the chemical composition of them, as it is dependent on which portion of body is located.

Biofluids such as blood products, human saliva, serum, plasma and urine are used in research and clinical studies and in in translational and biomarker research. Also, biofluid samples can be analyzed in medical contexts for diagnostic evaluation, helping to identify diseases and conditions. 

Biofluids, including blood, urine, saliva, and other bodily fluids, are essential for biomedical research. They provide valuable information about disease, drug effects, and overall health. Biofluids are used in various research areas, including drug discovery, biomarker studies, and the development of diagnostic tools.

Drug Discovery and Development

Biofluids are used to assess the concentration and effects of drugs in the body, aiding in the development of new therapies.

Biomarker Studies

Biofluids can be analyzed to identify and track measurable biological components (biomarkers) associated with specific diseases, helping in early detection and monitoring.

Diagnostic Tools

Biofluids can be used to develop diagnostic tests for various conditions, such as infectious diseases, cancer, and autoimmune disorders.

Research Applications

Biofluids are utilized in research across various fields, including:

  • Oncology: Studying cancer development and treatment responses. 
  • Infectious Diseases: Investigating the mechanisms of infection and developing antiviral therapies. 
  • Hematology: Studying blood disorders and their causes. 
  • Metabolism: Analyzing the metabolic profiles of individuals to understand disease pathways. 
  • Neurology: Studying the effects of neurological disorders on brain fluids and other bodily fluids. 
  • Reproductive Health: Investigating the effects of reproductive health conditions on biofluids. 

Types of Human Bio-Fluids