The endodermal layer, identified by markers AFP and FoxA2, will give rise to the digestive tract, lungs and bladder. Credit: Courtesy of Juan-Carlos Izpisúa Belmonte, from Cell Stem Cell, Oct. 1, 2009.
Since the first adult cells were converted into iPS cells, they have generated a lot excitement as an uncontroversial alternative to embryonic stem cells and as a potential source for patient-specific stem cells. Unfortunately, taking a patient's cells back in time is not only costly, but could be difficult when those cells are needed right away to mend injured spinal cords or treat acute diseases, and outright impossible when the effects of aging or chronic disease have irrevocably damaged the pool of somatic cells. "Patient-specific iPS lines have been advocated as a theoretically ideal clinical option to regenerate tissue but from a practical and cost-benefit aspect, this approach may not be feasible," says Izpisúa Belmonte. He hopes that the "large scale production and banking of cord blood-derived iPS lines in a publically available network could be a viable alternative for future clinical applications." With this in mind, Belmonte and his colleagues set out to transform hematopoietic stem cells isolated from cord blood into iPS cells. They not only successfully converted them using only two out of the four most commonly used factors — Oct4 and Sox2 — but also in less time than any other previously published methodology require. No matter, whether the researchers started with freshly collected cord blood or previously frozen samples, the resulting iPS cells were indistinguishable from human embryonic stem cells.
The mesodermal layer, identified by ASM, will form bones, muscles, connective tissue and the middle layer of the skin. Credit: Courtesy of Juan-Carlos Izpisúa Belmonte , from Cell Stem Cell, Oct. 1, 2009. "The population of cord blood cells used for reprogramming express reprogramming/stem cell factors at higher levels than those found in other adult somatic cells, which could explain why cord blood cells can be reprogrammed with less factors and in less time," says Izpisúa Belmonte. "It's almost like they are already half-way there." In addition, the cord blood-derived iPS cells, CBiPS cells for short, passed all standard tests for pluripotency: The gave rise to stem cell tumours known as teratomas and differentiated into derivatives of the three embryonic tissue layers, including rhythmically beating cardiomyocytes and dopamine-producing neurons. Izpisúa Belmonte's next goal is to convince cord blood cells to burn back time using methods that are considered safe for clinical applications in humans. The original protocols for producing iPS cells — including the one used by Belmonte and his team — rely on the integration of foreign "reprogramming" genes into the host-cell genome, a process associated with risks including mutation and the development of cancers after iPS-cell transplantation, limiting their therapeutic value. However, researchers are hard at work to develop alternative methods that allow them to reprogram cells without leaving any genetic traces, such as simply exposing differentiated cells to small molecules. "Several studies have already shown that this could be possible," says Izpisúa Belmonte. "If we can show they also work for cord blood cells, this certainly could be a step forward towards the clinical application of iPS cells. We should focus our efforts on this particular cell source, CBiPS cells, at least in the near future." .........
ZenMasterFor more on stem cells and cloning, go to CellNEWS at http://cellnews-blog.blogspot.com/ and http://www.geocities.com/giantfideli/index.html
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