12. tbl. 101. árg. 2015

Breakthrough in research on pluripotent stem cells and their application in medicine

Straumhvörf í rannsóknum á fjölhæfum stofnfrumum og notagildi þeirra í læknavísindum

Embryonic stem cells are, as the name indicates, isolated from embryos. They are pluripotent cells which can be maintained undifferentiated or induced to differentiate into any cell type of the body. In 1998 the first isolation of human embryonic stem cells was successful and they became an interesting source for stem cell regenerative medicine. Only 8 years later pluripotent stem cells were generated by reprogramming somatic cells into induced pluripotent stem cells (iPSCs). This was a revolution in the way people thought of cell commitment during development. Since then, a lot of research has been done in understanding the molecular biology of pluripotent stem cells. iPSCs can be  generated from somatic cells of a patient and therefore have the same genome. Hence, iPSCs have great potential application in medicine, as they can be utilized in disease modelling, drug screening and cell replacement therapy.

Figure legends

Figure 1. Overview of the isolation of embryonic stem cells. The blastocyst forms on day 5 after fertilization of an oocyte. The inner cell mass, surrounded by the trophectoderm, develops into an epiblast that subsequently develops into an embryo if the blastocyst is able to implant in the uterine wall. If the inner cell mass is isolated and cultured under defined conditions, the cells will grow in colonies. They are pluripotent and are called embryonic stem cells (ESCs). Depending on the culture conditions they can be either maintained indefinitively as pluripotent cells or they can be differentiated into a specific cell type.

Figure 2. iPSCs. Induced pluripotent stem cells (iPSCs) are generated by reprogramming somatic cells which involves de-differentiation. iPSCs have the advantage over hESCs in having the same genome as the original somatic cells from a patient. These iPSCs could therefore provide us with a useful source in regenerative medicine. Correction of a specific mutation that causes a disease is possible in iPSCs that could then be directly differentiated into the specific cell type required for cell replacement in the patient. iPSCs from patients can also be utilized to obtain a better knowledge of molecular mechnisms underlying the disease. iPSCs generated from patients are already being utilized in drug screening.

Figure 3. Directly converted cells. A somatic cell can be directly converted to another somatic cell without having to reprogram it first into a pluripotent stem cell. Initially, this was achieved by reprogramming somatic cells into an intermediate stage. Subsequently, a direct conversion of a somatic cell into another differentiated cell became successful. An example is given of a conversion into cardiomyocytes where the transcription factors Gata4, Mef2c, Tbx5 og Hand2 have been introduced, essential factors for cardiomyocyte induction.

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