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Abstract
Since induced pluripotent stem cell (iPSC) was first in-troduced by Yamanaka in 2006, it took only six years to win a Nobel Prize for his pioneering work. It is unusual to win a Nobel Prize for such recent research with a short history. Many scientists and clinicians are interested in iPSC for its potential application. Significant progression in this field has been made, while there remain many hurdles to overcome for application of iPSC technique in real clinics. In this review, the concept of reprogramming and the basic techniques of iPSC generation will be discussed for the reader's convenience, followed by discussion of recent progress, followed by the topics of “disease modeling” and “cell therapy” with iPSC in the second half of this article. Several examples of rheumatologic application of iPSC will be provided in the main text. If rheumatologists could understand the merits and potentials of iPSC, opportunities for innovative research and therapy can be expanded.
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Figure 1.
Vector structure of 4-in-1 lentivirus. 4-in-1 lentiviral vector contains 4 Yamanaka factors of Oct4, Klf4, Sox2, and c-Myc.
Figure 2.
Overall process of reprogramming. 293 T cells are used for production of 4-in-1 lentivirus. Lentivirus is transduced into dermal fibroblasts. After 1∼2 weeks, cells are transformed into stem cell like morphology. After 2∼3 weeks, stem cell colonies are formed and then picked up for cultivating stem cell lines.
Figure 3.
Summarized images during the process of iPSC reprogramming. Fibroblast begins to be changed into the shapes of self-proliferating and colony-like feature. Background fibroblasts are not reprogrammed so they remain spindle shapes. Generated three colonies are positive for pluripotency markers.
Figure 4.
Pluripotency markers are positive at generated clones. Immunofluorescence staining shows positive pluripotency markers such as Nanog, SSEA4, Sox2, Tra-1-81, Oct4, Tra-1-60. Embryonic stem cells and iPSC are alike in positivity of immunofluoresence study.
Figure 5.
Various levels of studies with disease-specific iPSC. OA FLS and RA FLS are compared with each other at fibroblast level. They are also studied when they are reprogrammed into iPSC clones. They can be differentiated into target disease cells such as chondrocytes and osteocytes. If we could find any differences in OA&RA iPSC-differentiated chondrocytes, it would be a promising methodology for exploring disease mechanism.
Figure 6.
An example of application of iPSC in disease modeling in future. iPSC from patients are differentiated into syno-viocytes, T cells, B cells and so on. After methotrexate is added in culture dishes, and then the effects of MTX on target cells could be studied.
Table 1.
Application of iPSC technique in disease modelling
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