Biomedical Engineering Reference
In-Depth Information
incurable disorders of the central nervous system (CNS) will have an unprece-
dented social and economic impact on society and the health care systems. In light
of this prospect, regenerative medicine depends on innovative strategies and
medical breakthroughs that can directly translate into novel therapeutics.
The human brain is characterized by enormous cellular and synaptic complexity
and any attempt for repairing or replacing nervous tissue is among the most
formidable goals in medicine. Neurons in the human brain are postmitotic and as
old as the diseased patient [
1
]. In general, the human CNS has limited regenerative
potential after injury and the pathobiology of neurodegenerative diseases is
intricate and difficult to study. In most cases, human samples are derived from
postmortem tissue with inherent problems such as poor tissue preservation and
lack of standardization. In addition, postmortem specimens often reflect the end-
stage of a given disease thereby limiting the study of prodromal changes.
The clinical manifestations of CNS diseases are determined by the underlying
anatomical location of the lesion, the affected cell type(s), the age of onset, genetic
background (familial or sporadic), and the environmental context (e.g. toxins,
pesticides, cellular stressors). With regard to understanding disease etiologies,
unraveling the interplay between complex genetic and environmental factors is
particularly challenging. Available drugs for the treatment of neurological and
psychiatric diseases are limited in that they only provide symptomatic relief but fail
to target the underlying disease cause. Currently, the development of novel drugs in
the pharmaceutical industry particularly for CNS diseases is experiencing major
difficulties because of the poor success rate of drugs entering clinical trials [
2
].
This is in part due to the limited predictive value of small animal models for drug
discovery emphasizing the fact that rodent models often do not recapitulate the
critical aspects and peculiarities of the human condition [
2
-
6
]. Together, it is
apparent that cell therapy, drug discovery, and mechanistic studies of human
disease would greatly benefit from readily accessible live human neural cells
amenable for basic research in a laboratory setting.
Human embryonic stem (ES) cells are the prototypical pluripotent cells and were
first isolated by Thomson and colleagues [
7
]. Because of the ethical issues associated
with the derivation of ES cells from human embryos, only a few laboratories were
able to create such cell lines following strictly regulated guidelines. In addition, the
dependence on limited embryo material did not allow the prospective isolation of
human ES cell lines representing the large variety of familial and sporadic human
diseases. The more recent discovery by Yamanaka and colleagues that human
somatic cells can be reprogrammed into embryonic-like iPS cells by a few defined
transcription factors represents a major breakthrough for biomedical research [
8
].
Nuclear reprogramming and the streamlined production of iPS cells hold great
promise for clinical cell therapy and disease modeling. The availability of experi-
mental platforms with functional human neurons derived from affected patients will
greatly advance high-throughput and high-content screening efforts and drug dis-
covery [
9
]. Ultimately, routine access to patient- and disease-specific iPS cells will
pave the way to rigorous cell therapy and tissue engineering paradigms and realize
the concept of ''personalized medicine'' in the twenty-first century.
