Wednesday, 11 April 2012

HOW TO REGROW A LIMB 101

Kaiya Ferguson
42634281

What many consider to be the final frontier in medicine is increasingly becoming a hopeful reality, thanks to research carried out in April 2011 at the Korean Gwangju Institute of Science and Technology. Researchers Darren R. Williams and Da-Woon Jung have developed a simple chemical blend, which has for the first time, encouraged the development of cells required for appendage regeneration in mammals[2]

 This newfound process that was developed on mice, targets muscle fibres and provokes the process of dedifferentiation and multipotency in skeletal muscle, as previously observed naturally in urodele amphibians such as newts and salamanders[3]. In laymen’s terms, dedifferentiation is the process where cells become multipotent, i.e. achieve a stem cell like state, where they then separate into other forms of tissue.  In mammals, Williams and Jung have accomplished this by introducing various mixes of chemicals including L-ascorbic acid; Colchicine; Cytosine b-D-arabinofuranoside hydrochloride (AraC); Dexamethasone; 5-fluorouracil; b-glycerophosphate disodium; 3-isobutyl-1-methylxanthine (IBMX); Myoseverin; Myoseverin B; Nocodazole and Reversine into myoblast cultures[3]. Myoblasts are a type of embryonic cell, which generate other muscle cells such as skeletal, smooth and cardiac cells[1].  The rate of dedifferentiation in these cells was monitored through the observation of DNA synthesis in the nuclei, as different molecules were introduced[3]. The outcome of this was that a high measure of muscle differentiation was attained from chemical stimulation, along with the
 conversion of muscle cells to fat and bone cells.

Although the potential for dedifferentiation is present in all living cells, the capacity for such an action differs greatly between organisms, present most strongly in phylogenetically primitive vertebrates[3]. A clear example of this is the vast capability of limb regeneration and cellularization in plants. The cause of this can be attributed to gene expression in limbs and more specifically the genetic switches involved. Research been undertaken by The University of Chicago Medical Centre suggests that it is these switch sequences driving gene expression that, depending on the location and timing, hold the power to change gene expression and limb growth in organisms[6]. To understand how this information could potentially link to Williams and Jung’s research, genetic switches need to be understood. A genetic switch is in fact a protein, which modifies the expression of a gene by binding to a specific DNA sequence. Through this bond, the genetic switch can effectively ‘turn genes on and off’[4], controlling the ‘synthesis of a functional gene product’[5]. From this, it could be proposed that the chemical cocktail produced by Williams and Jung in fact had an effect upon the genetic switches within the mouse muscle fibres, essentially ‘turning on’ the gene expression and allowing dedifferentiation to occur.

So what does this mean for humankind? Williams and Jung’s work will affect regenerative medicine along with stem cell biology. By shedding more light onto the hot topic of limb regeneration, there is yet more hope that one day with this research, it will be conceivable for amputees to regrow limbs and perhaps heart attack patients to regenerate a stronger heart muscle. We shall have to wait and see.


References:
[1]            ATCC (2011), Myoblasts, Retrieved March 10, 2012, from http://atcc.custhelp.com/app/answers/detail/a_id/535/~/myoblasts
[2]            American Chemical Society (2011), Simple chemical cocktail shows first promise for limb re-growth in mammals. ScienceDaily. Retrieved March 10, 2012, from http://www.sciencedaily.com/releases/2011/04/110406122207.htm
[3]            Da-Woon Jung, Darren R. Williams. (2011), Novel Chemically Defined Approach To Produce Multipotent Cells from Terminally Differentiated Tissue Syncytia. ACS Chemical Biology, 2011; Retrieved March 10, 2012 from DOI: 10.1021/cb2000154
[4]            NCBI (2002), How Genetic Switches Work, Molecular Biology of the Cell. 4th edition; Retrieved March 12, 2012, from http://www.ncbi.nlm.nih.gov/books/NBK26872/
[5]            News Medical, What is Gene Expression, Retrieved March 12, 2012, from http://www.news-medical.net/health/What-is-Gene-Expression.aspx
[6]            University of Chicago Medical Center (2011), Genetic switch for limbs and digits found in primitive fish: Before animals first walked on land, fish carried gene program for limbs. ScienceDaily. Retrieved March 12, 2012, from  http://www.sciencedaily.com/releases/2011/07/110711151453.htm

Image Sources:
 Da-Woon Jung, Darren R. Williams. (2011), Novel Chemically Defined Approach To Produce Multipotent Cells from Terminally Differentiated Tissue SyncytiaACS Chemical Biology, 2011; Retrieved March 10, 2012 from DOI: 10.1021/cb2000154
Shiho Fukada (2008), Children in Recovery, Retrieved March 15, 2012 from http://www.shihofukada.com/#/china-earthquake/children-in-recovery/Amputee001
Palscience (2009), Can We Regenerate Our Body Parts?, Retrieved March 14, 2012, from http://palscience.com/science/can-we-regenerate-our-body-parts-science-say-yes-and-we-are-close/

















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