Feb. 21, 2013 Cell therapy is a promising alternative to tissue and organ transplantation for diseases that are caused by death or poor functioning of cells. Considering the ethical discussions surrounding human embryonic stem cells, a lot is expected of the so-called 'induced pluripotent stem cells' (iPS cells). However, before this technique can be applied effectively, a lot of research is required into the safety and efficacy of such iPS cells. VIB scientists associated to the UGent have developed a mouse model that can advance this research to the next step.
Lieven Haenebalcke (VIB/UGent): "iPS cells have enormous therapeutic potential, but require more thorough testing before they can be used for such purposes. Using our new mouse model, we can study which mechanisms determine the identity of a cell. This knowledge is essential before we can use cell therapy for regenerative medicine."
Jody Haigh (VIB/UGent): "If we want to give cell therapy a future, then we must continue this type of research and invest in the further development of such technologies. This will result in an improved insight into cellular identity and -- in the long term -- safer options of applying iPS cells or cells derived from iPS cells in clinical studies."
Cell therapy -- replacing cells to provide a cure
Cell therapy is the replacement of lost or poorly functioning cells in patients. For example, such cell therapies could be used to repair the heart muscle after a heart attack, joints affected by arthritis, the pancreas in diabetes or the spine in certain forms of paralysis. This requires cells that are able to multiply in the laboratory and that can be converted to healthy cells of the desired cell type. Human embryonic stem cells meet these criteria, but they are ethically controversial.
iPS cells -- a promising alternative to embryonic stem cells
Shinya Yamanaka recently developed a fairly simple method to reprogram differentiated cells -- such as skin cells -- back to stem cells, so-called "induced pluripotent stem cells" (iPS cells). This earned him the Nobel Prize for Medicine in 2012 (shared with John Gurdon). These iPS cells can be generated using only 4 "reprogramming factors."
As is the case with embryonic stem cells, these iPS cells can be used to produce other cell types, such as heart muscle cells or nerve cells. They can also be cultured indefinitely and there are no ethical objections as they are not obtained from human embryos left over after IVF, but from adult individuals. Furthermore, iPS cells are obtained from the patient and this reduces the risk of rejection during therapeutic applications.
Essential research possible
Before iPS cells can be used effectively and safely as a therapy, it is essential that we gain clear insight into which molecular mechanisms determine the identity of a cell; why and how a cell develops into -- for example -- a heart muscle cell, a nerve cell or a blood cell. In order to do so, Lieven Haenebalcke and Jody Haigh have developed a mouse model that will enable them to conduct this research. They succeeded in creating iPS cells from a variety of mouse cells. Furthermore, the new model allows the investigators to replace the 4 reprogramming factors in these iPS cells efficiently with specific genes in order to create targeted different cell types, such as functional heart muscle cells.
Lieven Haenebalcke (VIB/UGent): "It enables us to study in a relatively simple manner the molecules that play a role in the formation and the identity of various cell types. Using this knowledge, we can then manipulate the identity of cells in a more targeted fashion and then conduct pre-clinical tests to determine whether these new cells are suitable, for example to repair heart tissue or blood vessels."
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- Lieven Haenebalcke, Steven Goossens, Pieterjan Dierickx, Sonia Bartunkova, Jinke D’Hont, Katharina Haigh, Tino Hochepied, Dagmar Wirth, Andras Nagy, Jody J. Haigh. The ROSA26-iPSC Mouse: A Conditional, Inducible, and Exchangeable Resource for Studying Cellular (De)Differentiation. Cell Reports, 2013; 3 (2): 335 DOI: 10.1016/j.celrep.2013.01.016
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