Stem Cell Hemotoxicity Testing

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For decades, hemotoxicology has taken low priority for several reasons.

  • It was assumed that, particularly for anti-neoplastic drugs, the normal cells of the hematopoietic system are going to be affected and therefore it was a foregone conclusion that toxicity would occur and was considered a necessary risk.
  • Hemotoxicity was based on conventional toxicity practices and guidelines and therefore was only conducted as part of general toxicity during pre-clinical animal studies.
  • No high-throughput, non-subjective, standardized assays were available so that hemotoxicology could not be considered earlier in the pipeline than that used during pre-clinical studies.

HemoGenix® brought stem cell hemotoxicity testing into the limelight by introducing the HALO® Platform as a contract research service. HALO® was originally developed for drug discovery and development propelling hemotoxicity testing into the 21st century.

Hemotoxicity is not limited to anti-cancer drugs. Hemotoxicity can occur with any drug and virtually any chemical. Indeed, any agent that can affect cells during any stage of the proliferation pathway, has the potential to cause hemotoxicity. The reason is because the primary function of the lympho-hematopoietic system is to produce mature functional cells throughtout a person's life. The organization of the system allows this to occur because of the presence of a stem cell compartment and an amplification compartment. These 2 cellular compartments contain cell populations that exhibit varying degrees of proliferative potential. The more primitive the cell, the greater the proliferative potential. A cell also does not have to be in cell cycle to be affected by an agent. Such agents can affect primitive stem cells that are quiescent. Only when they are induced into proliferation will it be found that a defect has occured. The stem cells and those in the amplification compartments are the most sensitive to insults of any nature, whether it is by drug, chemical or radiation administration. The earlier an agent acts in the lympho-hematopoietic organizational hierarchy, the greater the toxicity and the broader and more dangerous the impact will be.

Other proliferative biological systems, including the cells of the gastrointestinal tract, the proliferating cells of the reproductive system, the skin and the corneal cells of the eye, all exhibit a similar organization structure to the lympho-hematopoietic system. (The latter is unique in that it produces at least 8 different types of functional cells compared to only 1 from the other systems mentioned). As such results obtained using lympho-hematopoietic target cells can be extrapolated to these other proliferating system, especially the gastrointestinal tract. The HALO® Platform provides a reproducible and reliable in vitro, non-invasive system to detect and measure changes in these primitive and early cell populations, and provides a unique decision-making tool to predict the affect of virtually any agent on different lineages of the blood-forming system. Our article entitled "Validation and Development of a Predictive Paradigm for Hemotoxicology using a Multifunctional Bioluminescence Colony-Forming Proliferation Assay" by I.N. Rich and K.M. Hall (Tox Sci 2005, 87/2:427-441 or go to Downloads Page) demonstrates how the HALO® Platform was validated and how the HALO® 7-Population Predictive Platform can predict not only the response of the lympho--hematopoietic system when specific cell populations are tested, but also its ability to predict in vivo starting doses for pre-clinical studies and human clinical trials prior to these ever taking place.

Detecting hemotoxicity using the HALO® Platform provides:

  • High validated predictability.
  • Highly sensitive assay systems.
  • Shorter time to detect hemotoxicity.
  • Determines which cells are directly affected by the agent.
  • Distinguishes between differential effects on normal and abnormal cells.
  • Correlation between in vivo and in vitro activity.
  • Determines circadian rhythm effects of drugs.
  • Interspecies comparisons.
  • Extrapolation to other proliferating systems.

 

HALO®, in combination with other HemoGenix® toxicity testing platforms, namely LUMENESC™ and LumiSTEM™, constitute the ComparaTOX™ Platfor for Predictive In Vitro Comparative Toxicity testing. Since the same ATP-based bioluminescence signal detection system is used for all three platforms, this unique and powerful in vitro, cell-based technology allows more than 50 primary cell types from 14 cell systems to be analyzed under high-throughput conditions in order for agents to be tested and their potential toxicities directly compared.

HemoGenix® offers two alternatives by which clients and customers can perform hemotoxicity testing using HALO®. Our high-quality, contract research service is designed to meet your requirements during all stages of drug discovery and development, from ADME/Tox screening to safety and risk assessment prior to and during clinical trials, thereby enhancing efficacy and safety of your product. We also provide contract service for environmental testing. Please refer to our Contract Services Section on our website.

Alternatively, our HALO® Platforms are available in numerous configurations of assay kits. If the cell population or combination of cell populations is not shown in our Hemotoxicity Catalog, please contact HemoGenix® because there is a good chance we can custom produce the assay kit you want at little or no extra cost.