Human Pluripotent Stem Cells in Pharmacological and Toxicological Screening: New Perspectives for Personalized Medicine

Abstract

Human stem cells provide an important novel tool for generating in vitro pharmacological and toxicological test systems. In the development of new targeted therapies, as well as in critical safety issues, including hepato-, neuro- and cardio-toxicity, animal-based tests are mostly unsatisfactory, whereas the use of in vitro model systems is limited by the unavailability of relevant human tissues. Human embryonic stem cell lines may fill this gap and offer an advantage over primary cultures as well as tissue-derived (adult) stem cells. Human embryonic stem cells represent an unlimited source for the production of differentiated somatic progenies and allow various stable genetic manipulations. As a new opening in personalized medicine test systems, the generation of induced pluripotent stem cell lines and their derivatives can provide patient- and disease-specific cellular assays for drug development and safety assessments. This article reviews promising human stem cell applications in pharmacological and toxicological screenings, focusing on the implications for personalized medicine.

KEYWORDS::

• cardiac toxicology
• developmental screening
• developmental toxicology
• genetic manipulation of stem cells
• hepatotoxicity
• human pluripotent stem cells
• neurotoxicity
• personalized in vitro cellular systems
• pharmacological and toxicological screening
• targeted drug development

Financial & competing interests disclosure

This work was supported by grants from Országos Tudományos Kutatási Alapprogramok (OTKA; NK72057), Egészségügyi Tudományos Tanács (ETT; 213-09), ES2Heart (OM00203/2007), STEMKILL (OM00108/2008), KMOP-1.1.2-07/1-2008-0003 and TÁMOP-4.2.2-08/1-2008-0015. Tamás I Orbán is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by grants from Országos Tudományos Kutatási Alapprogramok (OTKA; NK72057), Egészségügyi Tudományos Tanács (ETT; 213-09), ES2Heart (OM00203/2007), STEMKILL (OM00108/2008), KMOP-1.1.2-07/1-2008-0003 and TÁMOP-4.2.2-08/1-2008-0015. Tamás I Orbán is a recipient of the János Bolyai Scholarship of the Hungarian Academy of Sciences. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.