Preclinical studies of stem cell therapies are critical for FDA approval to begin clinical trials, but there currently are no guidelines that address this important area of preclinical research. Here are some tips to consider when designing translational cell therapy research:
- Ensure each step in the program is customized to the particular cell line, its actions, and the intended clinical use.
- Understand the cell product. Cell products must be well-characterized with established production processes, detection methods, and characterization specifications before the initiation of preclinical studies and must be the same as the product to be used in clinical trials.
- Animal models must be both clinically relevant and appropriate for preclinical study objectives.
- Animal model selection must consider biological relevance, activity, persistence, and migration/distribution, and all must be relevant to clinical use.
- Specialized animal models may be required (e.g., animal models for the targeted disease or the use of a specific immunocompromised model).
- Consider limitations of administering the clinically relevant dose and immunogenicity concerns.
- Ensure that the method of delivery does not confound toxicity.
- Develop, optimize, and validate translational biomarkers (e. g., morphology, surface, and/or genetic marker) and the methods for cell detection (e.g., PCR, IHC) during pilot studies. These methods must be robust, reliable, and sensitive.
- Thoroughly evaluate cell phenotypic stability in vivo to clarify the potential for tumorigenicity and/or ectopic tissue formation.
- Communicate with regulatory agencies on preclinical program designs and animal model selections before studies are initiated.
Strategic program planning and design for these unique cellular therapies lead to successful preclinical programs and ultimately, successful therapies.