85megakaryocytes, the mpl knockout mice did not present conventional CAMT human
disease (Hirata et al. 2013 ). This fi nding and other research indicated that patho-
physiological development processes might differ between humans and mice
(Carver-Moore et al. 1996 ; Ebert et al. 2012 ). Therefore, this difference reduces
direct translation from preclinical animal studies to clinical trials.
Since the early studies on iPSCs, iPSCs have been considered as a powerful tool
for in vitro and in vivo modeling of genetic disorder diseases. iPSCs can be used to
monitor the development of many diseases , such as hematopoietic, neurological,
cardiovascular, hepatic, and other inherited diseases (Ebert et al. 2012 ; Juopperi
et al. 2011 ). To date, several neurological disease models have been successfully
generated using iPSCs, such as models for amyotrophic lateral sclerosis (Dimos
et al. 2008 ), Down syndrome (Park et al. 2008 ), fragile X syndrome (Urbach et al.
2010 ), Huntington’s disease (Park et al. 2008 ; Zhang et al. 2010 ), spinal muscular
atrophy (Ebert et al. 2009 ), and Parkinson’s disease (Soldner et al. 2009 ). Soldner
and coworkers showed that human iPSCs become a more suitable cell source for
human disease modeling when fi broblasts from Parkinson’s disease patients can be
effi ciently reprogrammed and differentiated into dopamine rgic neurons (Soldner
et al. 2009 ). Patient-derived iPSCs could be also generated from other skin cells
(Dimos et al. 2008 ; Takahashi et al. 2007b ), neuronal cells (Dimos et al. 2008 ),
hematopoietic cells (Brown et al. 2010 ), and other cell sources (Sun et al. 2009 ).
The technology to establish human iPSC lines provides a basis to make clean the
mechanism of cellular reprogramming. It also helps further our understanding of
the safety and effi cacy of iPSCs differentiated from humans for next-generation
medicine.
The use of iPSCs for modeling disease has led to multiple benefi ts for the medi-
cal industry, especially for treatment of cancer and infectious diseases (Siller et al.
2013 ). iPSCs are now being use d to delineate the molecular events involved in can-
cer and tumorigenicity, such as the mechanism of their oncogenic potential (Ghosh
et al. 2011 ). Gore and colleges showed that human iPSC lines contain a majority of
protein-coding point mutations in the regions sampled as nonsynonymous, nonsense,
or splice variants. In addition, these mutations were causative effects in cancers
(Gore et al. 2011 ). Yoshida and coworkers also suggested that iPSC-derived hepato-
cyte-like (iPSC-Hep) cells are an appropriate model for hepatitis C virus infection as
they successfully used iPSCs generated from human hepatocyte-like cells to inves-
tigate the entry and genomic replication in iPSC-Hep cells (Yoshida et al. 2011 ).
Thus, iPSCs have become an important disease model that shows more advan-
tages than other classical models and provides an unlimited source of proliferating
cells for next- gen eration regenerative medicine (Fig. 4.3 ).
4.3.1.2 Drug Screening
Evaluation of human drug toxicity is a critical stage in the drug discovery process.
When a new drug is invented, the prediction of toxicity is a critical issue during
safety and effi cacy testing (Rubin 2008 ). Functional cells differentiated from human
4 New Trends in Clinical Applications of Induced Pluripotent Stem Cells