The article selected for this assignment is “Targeted Gene Correction of α1-antitrypsin Deficiency in Induced Pluripotent Stem Cells”, by Kosuke Yusa, et al., and was published as a Nature Letter on October 20th, 2011.1 This is a proof-of-principle study for a new technology developed by the authors for eventual application in cell replacement therapy. The authors used a novel combination of zinc finger nuclease and piggy-Bac methodology in human induced-pluripotent stem cells (iPSCs) to correct a single point mutation in the α1-antitrypsin gene that is known to be responsible for α1-antitrypsin deficiency in humans. After successfully correcting the point mutation in several patient iPSC lines, the authors were able to differentiate the lines into fully hepatocyte-like cells in both structure and function. After in vivo transplantation into mouse livers, the hepatocyte-like cells distributed throughout the lobes of the liver and appeared to be functioning normally. The authors assert that their work is the first proof of principle for combining a genetic correction and human iPSCs in a way that is clinically applicable for cell therapies in which a patient’s own cells are isolated, subjected to corrective gene therapy, and then returned to the patient.
I selected this article for the midterm assignment because I was interested in learning more about research with human induced pluripotent stem cells and cell replacement therapy after the class session and paper discussion with Dr. Melissa Wong about intestinal stem cells. In addition to introducing a new method aimed at iPSC replacement therapy, the authors also test their method against several potential problems that could prevent it from being clinically applicable. Overall,...
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References
1. Yusa, K. et al. Targeted gene correction of α1-antitrypsin deficiency in induced pluripotent stem cells. Nature 478, 391–394 (2011).
2. Fairchild, P. J. The challenge of immunogenicity in the quest for induced pluripotency. Nat. Rev. Immunol. 10, 868–875 (2010).
3. Lu, X. & Zhao, T. Clinical Therapy Using iPSCs: Hopes and Challenges. Genomics Proteomics Bioinformatics 11, 294–298 (2013).
4. Kim, A. & Pyykko, I. Size matters: versatile use of PiggyBac transposons as a genetic manipulation tool. Mol. Cell. Biochem. 354, 301–309 (2011).
5. Woltjen, K. et al. piggyBac transposition reprograms fibroblasts to induced pluripotent stem cells. Nature 458, 766–770 (2009).
6. Urnov, F. D., Rebar, E. J., Holmes, M. C., Zhang, H. S. & Gregory, P. D. Genome editing with engineered zinc finger nucleases. Nat. Rev. Genet. 11, 636–646 (2010).
The cells unique nature has scientists intrigued to do research with the focus of finding a way that these cells can be used to replace patients’ injured or diseased tissues. Advancement is made to all the three types of stem cells namely embryonic stem cells, adult stem cells in addition to induced pluripotent cells. Embryonic cells are the building blocks of an embryo that is developing, and can develop into almost all body cell types. Somatic cells are found in the body tissues. They renew and regenerate in healthy bodies. The third type which is induced pluripotent is genetically modified embryo cells from skin cells.2 Research on these cells are geared towards saving humanity; a noble course.
Alpha-1 Antitrypsin Deficiency is the most common potentially fatal genetic disorder of adult Caucasians in the U.S. The incidence of Alpha-1 Antitrypsin Deficiency is suspected to be between 1/2500 and 1/3000. (Alpha-1 Foundation.) Alpha-1 Antitrypsin Deficiency c...
Cancer is a disease in which cells multiply out of control and gradually build a mass of tissue called a tumor. There has been a large amount of research dedicated to the treatment and cure of cancer. Several types of treatments have been developed. The following are just some of the major examples of cancer therapy: surgery, chemotherapy, radiation therapy, biologic therapy, biorhythms, unconventional treatments, and hyperthermia. Each type of treatment is discussed in detail below.
Stem cell research began in 1956 when Dr. E Donnall Thomas performed the first bone marrow transplant (“Adult stem cells are not more promising,” 2007). Since that time, research has evolved into obtaining cells from a variety of tissues. According to stem cell research professors, Ariff Bongso and Eng Hin Lee (2005), “Stem cells are unspecialized cells in the human body that are capable of becoming cells, each with new specialized functions” (p. 2). Stem cells are in various adult tissues, such as bone marrow, the liver, the epidermis layer of skin, the central nervous system, and eyes. They are also in other sources, such as fetuses, umbilical cords, placentas, embryos, and induced pluripotent stem cells (iPSCs), which are cells from adult tissues that have been reprogrammed to pluripotency. Most stem cells offer multipotent cells, which are sparse...
There are many different types of stem cells that are being looked at for research. These include embryonic stem cells, adult stem cells, and induced pluripotent cells. Embryonic stem cells are cells that have the potential to produce many different cells in the body. They are cells that are tak...
“Top Ten Things to Know About Stem Cell Treatments.” Www.closerlookatstemcells.org ISSCR. Web 1 November 2013
Those who favour stem cell research are optimistic about the continued developments in stem cell research will open doors to many breakthrough discoveries in biomedical science. The scientific and ethical questions arise as rapidly as the reaching of milestones in stem cell research. There are two main types of stem cells, namely embryonic stem cells and adult stem cells. Adult stem cells are undifferentiated cells in our body. But they have restricted-range of cells that they can further differentiate. On the contrary, embryonic stem cells have the ability to differentiate into nearly two hundred cell types in the human body, called pluripotency. The process of harvesting embryonic stem cells involves destruction of embryos (Mooney, 2009).
In the past 40 years, scientists have developed and applied genetic engineering to alter the genetic make-up of organisms by manipulating their DNA. Scientists can use restriction enzymes to slice up a piece of DNA from an organism with the characteristics they want and spliced (joint) to a DNA from another organism. DNA that contains pieces from different species is called recombinant DNA, and it now has different genetic material from its original. When this DNA inserted back into the organism, it changes the organism’s trait. This technique is known as gene-splicing (Farndon 19).
Encyclopedia of Stem Cell Research.
Eggleson, K. E. (2012). Stem Cell-Based Therapies: Promises, Obstacles, Discordance, and the Agora. Perspectives in Biology and Medicine, 55(1), 1-25.
Li, Julang. "Mechanisms Involved in Targeted Gene Replacement in Mammalian Cells." Genetics. Vol. 156, 809-821. Oct. 2000.
Although humans have altered the genomes of species for thousands of years through artificial selection and other non-scientific means, the field of genetic engineering as we now know it did not begin until 1944 when DNA was first identified as the carrier of genetic information by Oswald Avery Colin McLeod and Maclyn McCarty (Stem Cell Research). In the following decades two more important discoveries occurred, first the 1953 discovery of the structure of DNA, by Watson and Crick, and next the 1973 discovery by Cohen and Boyer of a recombinant DNA technique which allowed the successful transfer of DNA into another organism. A year later Rudolf Jaenisch created the world’s first transgenic animal by introducing foreign DNA into a mouse embryo, an experiment that would set the stage for modern genetic engineering (Stem Cell Research). The commercialization of genetic engineering began largely in 1976 wh...
Dec. 2013. http://www.disabled-world.com/artman/publish/genetic-engineering.shtml Park, Tristen S., Steven A. Rosenberg, and Richard A. Morgan. "Treating Cancer with Genetically Engineered T Cells." National Center for Biotechnology Information. PubMed Central (PMC), 12 June 2011.
...there are some risk factors in using stem cell for therapeutic approaches, hematopoietic stem cell therapy by bone marrow transplantation has already been proofed to be safe if donors’ background and screening, cell contamination, HLA matching and opportunistic or nosocomial infections during immunocompromised period were carefully monitored and controlled. Still, other types of stem cell therapies, despite of their good therapeutic efficacy, are remain in experimental stage and need more data to support and demonstrate the safety in clinical trials. More understanding of stem cell biology is also required in order to keep stem cell under controlled and avoid some complications that they might cause. So, to pave the way for successful stem cell therapy, research in this extent is needed to pursue to maximized therapeutic efficiency with highest safety in patients.
In the end, gene therapy in humans needs to come a long way before it will be widely accepted, but there is great potential in the technology and it needs to be pursued. Bibliography Anderson, W. F. (1992). The Species of the World. Human Gene Therapy -. Science, 256 (5058), 808-813.