Stem cells used to seed trachea transplant
November 26, 2008 by Kevin Graham
In a recent report published in the medical journal The Lancet, European researchers detailed their success in transplanting a trachea, seeded with the patient’s own stem cells, to restore breathing function to a young Columbian woman named Claudia Castillo (left). This discovery is noteworthy because it marks the first time a patient’s own stem cells were used in the reconstruction of their airway. Since the patient’s own cells were used, complications that arise from immune system rejection of the donated tissues were avoided.
Castillo had a damaged airway leading to her left lung. She was unable to draw enough air through the damaged airway to perform even basic daily activities. To generate a transplantable tissue the research team started with a donated trachea which they then stripped off all of the living cells. Once the cells were removed a protein scaffold remained which they then seeded with stem cells from the Castillo’s own bone marrow, and more mature cells from the patient’s healthy airway. These cells used the scaffold to grow and develop a new tissue with the appropriate size, physical and functional characteristics of a human trachea. Once the trachea was developed the transplant proceeded in the same manner as a normal donor – recipient transplant. The key to this successful transplant is that since the cells lining the trachea originated from the patient herself she will not have take immunosuppressive drugs for the rest of her life in order to avoid rejecting the new tissue.
This exciting discovery highlights the potential of using adult stem cells, harvested from the patient that requires them, to repair or replace damaged tissues. The most difficult part of utilizing stem cells from any source is coaxing them to produce the right cell types, performing the right functions, in the right orientation and structure. The use of natural protein, or artificially designed, three-dimensional scaffolds is one of the ways that this problem is being addressed. These scaffolds mimic the natural three-dimensional environment that stem cells would normally develop in, and seem to be able to provide or induce the necessary signals to control stem cell growth and maturation.
One word of caution though, don’t get too caught up in this one breakthrough just yet! Even the people that did the research admit that there is still a lot of work to be done before stem cells can be routinely utilized for even this one type of transplant. The researchers know that the patient’s stem cells repopulated the donor scaffold to create the new trachea, but they don’t know if after the transplant was completed if the cells produced from the stem cells were the key to the grafts success, or if other cells from the patient’s body have now taken over the graft, making the stem cells redundant.
Further experiments will be needed to address these questions, and to extend the positive results from the trachea transplant to other more complex tissues or organs. This recent discovery has certainly highlighted though that what was once a distant dream, repairing our damaged bodies with stem cells, is quickly emerging as a reality.
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Rett Syndrome and induced Pluripotent Stem cells goes “Green”
June 17, 2009 by Aaron Cheung
Stem cell researchers at The Hospital for Sick Children have now devised a method, reported in the scientific journal Nature Methods, that will facilitate the generation of induced Pluripotent Stem (iPS) cells. I have previously blogged about the promise of iPS cells (see related articles). iPS cells are cells which have been reprogrammed from a differentiated somatic cell (such as your skin cells) to a pluripotent stem cell (like an embryonic stem cell, only that you don’t need to use embryos!). The generation of iPS cells is inherently very rare which occurs at a frequency of about 0.01% meaning you can generate about one iPS cell line out of hundred thousand cells. Out of which, many lines fail to satisfy the different rigorous tests necessary to be given the prestigious name of “iPS cell”.
A group led by Dr. James Ellis, and lead author Dr. Akitsu Hotta, at The Hospital for Sick Children has generated a reporter, named EOS, that will facilitate the generation of iPS cells for both mouse and human. The reporter has DNA elements (called promoters) that will drive the expression of a fluorescent protein (GFP) and an antibiotic resistance gene (puromycin) that will only turn on in pluripotent stem cells, but remain off in differentiated cells. Therefore, scientists can now generate iPS cells from different sources and the iPS cells will literally “light up with a green colour” once reprogramming has been achieved. Furthermore, by adding puromycin to your culture, it will keep the iPS cells in a pluripotent state as iPS cells will normally spontaneously differentiate.
To demonstrate the applicability of EOS, Ellis also derived iPS cells from patients who have a neurodevelopmental disorder called Rett Syndrome. Rett Syndrome is an Autism Spectrum Disorder which affects almost exclusively females at an incidence of 1 in 10,000 and is one of the leading causes of mental retardation in girls. These Rett Syndrome iPS cells were green when placed under a fluorescent microscope and Ellis demonstrated that neurons can be generated from these Rett Syndrome iPS cells, the cell type affected in Rett Syndrome.
In conclusion, the EOS reporter will facilitate the generation of iPS and will be particularly useful for new labs going into this rapidly developing field. Furthermore, Rett Syndrome iPS cells that were also generated in this study will be invaluable for future drug screens that may be beneficial to those with Rett Syndrome.
Article:
Hotta, A. et al. Isolation of human iPS cells using EOS lentiviral vectors to select for pluripotency. Nature Methods 6, 370–376 (2009).
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Breakthrough of 2008 – Reprogramming
A New Era for Disease Modeling and Drug Screening
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Stem Cell Origins
Cancer stem cells
Stem Cells and the Nervous System
