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Personalized Clinically Relevant Chemically Induced Pluripotent Stem Cells (CiPSTM)
At DNAmicroarray, Inc. we are advancing human iPS cell
derivation with modifications that are compatible with eventual clinical
translation of this technology. Our
prototype human Chemically Induced Pluripotent Stem (CiPS) cells and related
technologies hold great promise for practical generation of disease and patient
specific cell lines and regenerative cell therapy. 1) Problem:
retroviral gene transduction
The retroviruses used to insert the genes into iPS cells could cause tumors in
tissues grown from the host iPS cells.
Solution:
use of small molecules for chemically induced pluripotent cells (CiPS)
It is generally believed, and supported by our recent discoveries, that use of
small molecules for induction of iPS signal transduction pathways may replace
the need for gene transduction. This has been achieved using an iPS specific
modeled microenvironment niche and a focused library of small molecules that
induce iPS pathway gene expression. We are actively enhancing the ability of our
candidate compound cocktails for chemical induction of pluripotent status
in adult skin cells (CiPS). This is achieved with further chemical genetics
screens and exploratory R&D in structure assisted drug design, structure
activity relationship (SAR), medicinal chemistry, and target validation. 2) Problem:
low efficiency & slow process
The overall procedure has lower than practical levels of efficiency (1 in
5000-10000 cells), taking 14-24 days to identify and isolate colonies of
possible iPS Phenotype. Solution:
use of optimized induction protocols
work is in progress to use
modern and controlled 3D hydrogel modeled microenvironment niche culture systems
to provide for enhanced high efficiency CiPS procedures with practical
efficiency rates (i.e.
approaching greater than 5-10%) and faster overall induction time of the process of
reprogramming (i.e.
days instead of weeks). 3) Problem:
identification based on genetic selection of drug resistance
The need for transgenic donor cells and drug resistance selection of iPS cells
makes iPS procedures less prone to clinical applications.
Solution: use of non
genetic and/or morphological identification
Identification of iPS cells based on the morphology of iPS colonies has been
in-part devised in mouse and in human iPS experiments (1,2,3). For clinical
applications, however, we are exploring replacement of these visual
identification of morphological characteristics of iPS colonies with more
objective biomarker based high sensitivity and specificity identification means
of CiPS cells that will be incorporated into a standardized “point of care”
kit system. For
further information and update on our progress in this area please refer to our Tech.Pipeline
page. For collaboration proposals, please email our Technology Access Program (TAP@dnamicroarray.com).
Click here for "5 Things to Know Before
Jumping on the iPS Bandwagon" (Cyranoski D., 2008, Nature, 452:406-408)
References 1. Takahashi, K. et. al,
(2007), Cell 131:1–12. 2. Junying Yu et al. (2007) Science 318:
1917-1920. 3. Meissner, A et al. (2007) Nature
Biotechnology 25 (10): 1177-1181. |
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