I am a new member of OpenWetWare!
- Alessandro Testori
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I work in the Your Lab at XYZ University. I learned about OpenWetWare from did a web search, and I've joined because BIOSOMATIC CELLULAR ENGINEERING: The various tissues of the human body contain small population of stem cells whose function is to continually produce differentiated cells that carry out the specific functions of the tissue. The differentiated cells have a limited lifespan from a few months to a few years but eventually die off and need to be replaced by new cells. For example the red blood cells that live in the blood last on average 120 days after which they are eliminated and replaced by newly produced red blood cells. The red blood cells are produced by populations of stem cells in the bone marrow. the hematopoietic stem cells produce reticulocytes which in turn produce the mature red blood cells. In the skin, there is a layer of stem cells at the base which produces the differentiated keratinocytes which then move up, towards the surface where eventually they are exfoliated and lost. The process takes four months or so. The stem cells have a much longer lifespan than the differentiated cells, and can resupply the tissue they control for many years. All the organ systems and tissues in the human body work more or less in this way. The problem is that when the stem cells falter and stop producing enough differentiated cells to replenish the cells lost by the tissue through wear and tear, the function of the tissues and organs deteriorates and the organism ages. Just look at your own father, mother, grandfather and grandmother: you will notice that as the years go by they seem to “shrink” and get smaller and smaller. My own great grandmother was a large woman up to when she was 70 yo, but later she began to shrink and when she died at 101 years of age she was tiny, less than half her original weight and she had lost more than 15 cm (6 inches) in stature. The bone marrow is the typical example of a tissue that loses functionality with increasing age. In the bone marrow, there is a change in the ratio of fat to cellular bone marrow with age, which has been well known since the turn of the twentieth century . Basically, as one ages, the bone marrow contains more adipose cells and less mesenchymal and hematopoietic stem cells compared to the bone marrow of a young individual (see also references at the end of this letter).
I do not know what process causes the stem cells to eventually peter out. Some scientists think it is the telomeres, but in my opinion, this is not correct. Other groups have found that there is a genetic base to the aging of stem cells in the hematopoietic system (references found at the end). In all honesty I do not know what the cause of the process is. However I do not think this is essential. All we need to do is to take a “young” stem cells (say from a 20 yo person) and copy it. I am suggesting we manufacture human stem cells from scratch, starting from chemicals and ending up with a copy of a young stem cell. The stem cell is custom-tailored to a person, displaying the same surface antigen and HLA as those of the person. It is an exact copy of a that person's stem cell. The “copy” stem cell is then reimplanted in the tissue where the “original” came from. In this way the tissues and organs of the whole body are repopulated with “young” stem cells, which continue to repopulate the tissues maintaining homeostasis, the proper balance, and keeping the organism youthful. Because the cells are exact copies of the originals they will not be rejected and there will be no need for immunosuppresant drugs.
This may seem far-fetched, but we now have the disciplines of SYNTHETIC BIOLOGY and NANOTECHNOLOGY and a whole bacteria has been built from scratch in the lab by Dr. Craig Venter's group. If a bacteria can, why not a mammalian cell? The UK government is investing 1 million pound sterling to create a synthetic yeast cell (www.syntheticyeast.org) by 2017. Additional technologies that could help are3D PRINTING (www.3Dsystems.com), done at the nanoscale level.
NOTE: why does the body work in this way. If a mutation hits a stem cell it will be retained in the body for a long time and may cause a cancer. If a mutation hits a differentiated cell, it is no big deal, because after a few months that cell is lost or destroyed and with it any dangerous mutation. Therefore it makes sense for the body to keep a large number of “disposable” cells and only a few long lasting stem cells.
AN ALTERNATIVE APPROACH: we could also learn by looking at how nature does biosomatic cellular engineering. When Salamanders lose a leg, they convert adult differentiated cells back to an embryonic undifferentiated state. These cells then migrate to the site of injury where they regenerate the missing part. If we cannot manufacture entire stem cells from raw chemicals, plan B would be to re-program somatic cells in a similar fashion. Dr Jose Cibelli has been working on a similar set of problems http://www.reprogramming.net
Realizing this vision will of course need much computer power, automation of the process through nanotechnology and much money. I never said this was going to be easy. To quote the great genius aircraft designer Burt Rutan: “Confidence in nonsense is required to make a real breakthrough”. (watch him say it at http://www.youtube.com/watch?v=4kakrZ5w50s)
A TREATMENT FOR GENETIC DISEASES
for this explanation we will use Werner's syndrome which is caused by a mutation in a DNA helicase gene. But the same approach would work for Progeria (caused by Lamin A gene mutation) or for that matter for any disease caused by mutation in a single gene. Both Werner's and Progeria are disease of premature or accelerated aging.
The steps are
1)collect hematopoietic and mesenchymal stem cells from a healthy donor (who does not have the disease) who is a match in the HLA and ABO systems with the recipient. 2)Administer chemotherapy to the recipient, destroying his/her white blood cells and mature immune system, but without ablating the bone marrow. 3)Transplant the hematopoietic stem cells of the donor into the recipient and start immunosuppresant therapy to prevent rejection of the transplant. 4)Once the recipient has accepted the donor cells and the bone marrow of the recipient is a chimera of the original cells and the donor cells, immunosuppression can be stopped and the mesenchymal cells from the donor can also be infused and will not be rejected. 5)Now the recipient is a chimera in both hematopoietic and mesenchymal cell lines. However the cells of the Donor that do not carry the DNA helix mutation will slowly take over as they hold a proliferative advantage. 6)In this way, the mutation causing the disease has been complemented by providing cells that carry the wild type gene.
Attached are detailed clinical protocols explaining the process.
1) Geiger H, Rudolph KL. Aging in the lympho-hematopoietic stem cell compartment. Trends Immunol. 2009 Jul;30(7):360-5. 2) Geiger, H, Rennebeck G and Van Zant G, Regulation of hematopoietic stem cell aging in vivo by a distinct genetic element. Proc. . Acad. Sci. USA 2005 Apr 5; 102 (14): 5102-7 3) Geiger, H and Van Zant G. The aging of the lympho-hematopoietic stem cells. 2002 Apr 3(4): 329-33 4) Smith, JA and Daniel R. Stem Cells and Aging: A Chicken-or-the Egg Issue? Aging Dis. 2012 June; 3(3): 260–268.
5) Van zant, G. Genetic control of stem cells: implications for aging. Int J. Hematol 2003 Jan;77(1):29-36
6) Gazit R, Weissman IL and Rossi DJ. Hematopoietic stem cells and the aging hematopoietic system. Semin Hematol, 2008 Oct;45(4):218-24.
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- Goldbeter A and Koshland DE Jr. An amplified sensitivity arising from covalent modification in biological systems. Proc Natl Acad Sci U S A. 1981 Nov;78(11):6840-4.
- JACOB F and MONOD J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961 Jun;3:318-56.
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