Tarheel Health Portal/Artificial Organs

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There are many deadly diseases that require patients to either seek an organ transplant or suffer the consequences of a failing organ, worst of which, is death. Every year in the United States, about 27,000 people die from end-stage liver disease, 120,000 from chronic lung disease, 112,000 from end-stage kidney failure, and 425,000 from coronary heart disease.[1] Even patients who acquire an organ transplant, still face the potential of rejection from the body. The solution to these issues could rest in the fairly new scientific advance of organs created from adult stem cells, built upon a scaffold. To delve into this topic, important keywords include decellularization and recellularization, pluripotent stem cells, scaffolds, and bioreactors. In a gist, a cadaveric organ is decellularized to make a scaffold and then recellularized with somatic stem cells (from the patient receiving the organ) through the use of a bioreactor. Some problems that could be encountered in this research is the fact that doctors would still need donors for the scaffolds. Regardless, the public audience should care very much about this topic mainly because it could result in a large decrease in deaths and larger increases in successful transplantation of organs. Surveying a couple of students at UNC, there are students who have relatives who have waited an entire year on the organ transplant waiting list. UNC students should be interested in in this research, mainly because no matter what race, size, religion, age, or gender, organ complications can strike anybody. Originally, only simple organs could be produced through this revolutionary process, but over time, more complex organs like the liver, are starting to be produced in a laboratory. It is only a matter of time before hearts are to be made from stem cells. This research is vital to the longevity of humans. Fortunately, there is a Human Pluripotent Stem Cell Facility in Chapel Hill.

The Procedure[edit]

Stem cells are cells that have the ability to differentiate and become more specialized cell types.[2] Once they specialize, they can multiply rapidly to produce useful tiisue. When experimenting with artificial organs, stem cells from bone marrow tend to be the most helpful. In post-natal (after childbirth) bone marrow, there are stem cells that aid in the formation of proper cells of skeletal tissues and create a hematropoietic microenvironment, which when where there are blood cells that give rise to other blood cells.[3] Bone marrow stem cells have already been used to restore damaged tissue in a heart.[4] Somatic stem cells are preferred over embryonic stem cells when considering the engineering of organs for transplantation, mainly because embryonic stem cells remain totipotent (able to differentiate into any cell type) for only a short while after extracted from the embryos.[5]The ethical issues regarding embryonic stem cells also restricts in-depth research.

Stem cells one day after extraction from the body.
Stem cells after 3 days after extraction from the body.

For the actual production of an organ, the stem cells need to be recellularized onto a backbone type structure to make the organ called a scaffold. These scaffolds promote the reconstruction of functional tissue and first involve the decellularization of donor organs.[6] In normal orthotopic transplantation, the common treatment for organ failure, donor organs have to have a variety of different characteristics to be able to be transplanted into a patient who needs the organ. The organ from the donor has to match the biological environment of the patient. A lot of donor organs, although unsuitable for orthotopic transplantation, can provide a good scaffold for artificial organ transplantation. Because artificial organs are produced from the stem cells of the patient, the patient does not run the risk of nonadherence, or rejection. The scaffold provides the template, but the ultimate organ is made from the stem cells that originally came from the patient him/herself.

To actually remove tissue remnants from the organ, a bioreactor is used. It removes all living cellular components, leaving the underlying extracellular matrix scaffold preserved.[7] This scaffold can only then be used as a template for the production of an organ for transplantation. Once preserved, somatic stem cells can repopulate (using a growth factor) the three dimensional scaffold to ultimately restore normal function and anatomical features. The stem cells are recellularized through an intraparenchymal injection, which is the injection of stem cells onto tissue that exists on the body wall of organs where the actual organ eventually rests. The stem cells then proliferate, making more and more cells, specific to the organ needed for transplantation through the use of a particular growth factor. The product of this process is then placed under an environmentally-controlled area where the tissue can have nutrients and certain metabolic necessities. As time goes on in the proper conditions, an organ specific to the patient whose stem cells were used to recellularize the scaffold, will have been produced.

Basic use of stem cells to produce organs

Experiments Conducted[edit]

Artificial Trachea Transplantation[edit]

This concept, although new, has gained the attention of many medical professionals. Dr. Paolo Macchiarini along with medical experts in the Department of General Thoracic Surgery in the Hospital Clinico de Barcelona have engineered a bronchus for transplantation. The patient was a 30 year old woman who suffered from end-stage bronchomalacia, which means that one of her bronchial tubes was “floppy” as a result of weak cartilage.[8] Because of her illness, her faulty bronchus needed to be replaced or she would face inevitable death. To make a new bronchus, patient stem cells and a scaffold from a donor organ were used to make a graft that allowed normal breathing. The transplantation improved the patient’s quality of life, allowing her to breath normally without the risks of rejection. Although she was not on any anti-donor antibodies or immunosuppressive drugs (which would have disallowed her immune system to attack a foreign organ), the graft well assimilated into her body, showing the efficiency and effective safety of using stem cells and a scaffold to produce a trachea.

Artificial Liver Transplantation in Rats[edit]

In comparison to a bronchus, the human liver deals with much more complex processes and functions. The annual death rate in the United States from liver disease is 27,000.[9] Currently, orthotopic liver transplantation is the only treatment, and unfortunately it is limited as a result of organ shortages.[10] Doctor Uygun with other medical staff from the Children’s Hospital of Pittsburgh, The Institute for Regenerative Medicine, and the University of Pittsburgh, demonstrated how liver grafts can be engineered and transplanted into rats, showing the potential for successful human trials in the future. In the actual experiment, the cells used successfully recellularized onto the scaffold and distributed along all the vessels and networks, creating an organ suitable for transplantation. Once the graft was implanted into the rat through surgery, it filled with blood and began to function like a normal liver. This experiment outlines the importance of researching new feasible treatments for organ disease. This experiment also demonstrates how the large pool of unsuitable donor organs can be used for the making of a new, artificial organ. Although this experiment is small scale (in the sense of rats), it definitely provides enough insight on the potential success of such a procedure.

Relevance to U.N.C. Community[edit]

UNC is gifted in having such a diverse community. From surveying a number of people from random sample groups, I can say confidently that anyone reading this blurb either has needed an organ transplant, knows someone who has, or at least understands the tediousness of the organ wait list. Readers should understand that further research and just a stronger interest overall, is needed to draw attention to this biomedical advance. With more support for this revolutionary concept, this method of treating organ disease could turn into the primary method of treatment. To decrease the number of deaths from organ failure, there need to be more organs available, better chances of post-operative success and safety, and more doctors with the skills to provide this treatment. Our community is gifted with resources and medically knowledgeable staff that can provide any reader with more insight in the topic. Although you may not need an organ right now, you very well could in the future. And if not you, then your relatives, friends, or even peers will need one. Although the topic is still relatively new, I strongly believe that artificial organ transplantation can decrease the numbers of deaths from organ failure by thousands.

A summary of reasons why this method should be employed:

  • Organs that are unsuitable for normal donor organ orthopic transplantation, can be used for scaffolds
  • Because the tissue of the artificial organ is produced from the patient's own stem cells, chances of nonadherence (rejection from the body) are slim to none
    • anti-donor antibodies or immunosuppressive drugs won't be necessary to combat complications that normally arise with donor organs being transplanted
  • Because all you need is a scaffold from cadavers, many more organs can be produced, reducing the need for an organ wait list
  • People will receive the organs they need much faster, ultimately reducing unnecessary suffering from their organ condition.
  • This research could produce even more advances in medicine

Further Readings[edit]

As a UNC reader, here are some places you can go for more information on the topic

  • The UNC Human Pluripotent Stem Cell Core Facility provides UNC scientists as well as outside collaborators with the services to learn more about research regarding embryonic stem cells and induced pluripotent stem cells.
  • If you suffer from organ disease, and think you need an organ transplant, please don't hesitate in seeking help from UNC's Center for Transplant Care.
  • The article titled, Disease-Specific Induced Pluripotent Stem Cells describes how stem cells can be used to replaced cells ridden with disease with healthy cells.
  • To see UNC's policies towards stem cell research, visit this website.
  • To learn more about specifically, stem cells that come from bone marrow and their practical applications for cancer, click here.
  • To learn more about how stem cells can be used to curb diseases such as renal disease visit this article.

References[edit]

  1. http://www.annualreviews.org/doi/abs/10.1146/annurev-bioeng-071910-124743 Badylak S. (2011), Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds
  2. http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2184.2004.00298.x/full Rippon H and Bishop A. 2004. Embryonic stem cells. Cell Prolif 37(1):23-34.
  3. http://onlinelibrary.wiley.com/doi/10.1634/stemcells.19-3-180/full Bianco P, Riminucci M, Gronthos S, Robey PG. 2001. Bone marrow stromal stem cells: Nature, biology, and potential applications. Stem Cells 19(3):180-92.
  4. http://www.sciencedirect.com/science/article/pii/S0140673603121101 Stamm C, Westphal B, Kleine H, Petzsch M, Kittner C, Klinge H, Schümichen C, Nienaber CA, Freund M, Steinhoff G. 2003. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. The Lancet 361(9351):45-6.
  5. http://onlinelibrary.wiley.com/doi/10.1634/stemcells.19-3-180/full Bianco P, Riminucci M, Gronthos S, Robey PG. 2001. Bone marrow stromal stem cells: Nature, biology, and potential applications. Stem Cells 19(3):180-92.
  6. http://www.annualreviews.org/doi/abs/10.1146/annurev-bioeng-071910-124743 Badylak S. (2011), Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds
  7. https://patentimages.storage.googleapis.com/pdfs/c9db950fbefdc862b741/EP1367892B1.pdf Hariri R, Geweben R, Stammzellen UKD, decellularises, renovation et repeuplement de tissus, preleves ed. Organs by stem cells. .
  8. http://www.sciencedirect.com/science/article/pii/S0140673608615986 Macchiarini P, Jungebluth P, Go T, Asnaghi MA, Rees LE, Cogan TA, Dodson A, Martorell J, Bellini S, Parnigotto PP. 2008. Clinical transplantation of a tissue-engineered airway. The Lancet 372(9655):2023-30.
  9. http://www.annualreviews.org/doi/abs/10.1146/annurev-bioeng-071910-124743 Badylak S. (2011), Whole-Organ Tissue Engineering: Decellularization and Recellularization of Three-Dimensional Matrix Scaffolds
  10. http://www.nature.com/nm/journal/v16/n7/full/nm.2170.html Uygun BE, Soto-Gutierrez A, Yagi H, Izamis M, Guzzardi MA, Shulman C, Milwid J, Kobayashi N, Tilles A, Berthiaume F. 2010. Organ reengineering through development of a transplantable recellularized liver graft using the decellularized liver matrix. Nat Med 16(7):814-20.