In the U.S., someone dies of heart disease every 33 seconds. Currently, heart disease is the number one cause of death in the U.S.; by 2020, this disease is predicted to be the leading cause of death worldwide.1 Many of these deaths can be prevented with heart transplants. However, only about 2,000 of the 3,000 patients on the wait-list for heart donations actually receive heart transplants every year. Furthermore, patients who do receive donor hearts often have to wait for months.2

The shortage of organ donors and a rise in demand for organ transplants have instigated research on artificial organ engineering.5 In Tokyo, Japan, cell biologist Takanori Takebe has successfully synthesized and transplanted a “liver bud,” a tiny functioning portion of a liver, into a mouse; his experiment was able to partially restore liver function.3 Dr. Alex Seifalian from University College London, who has previously conducted artificial nose transplants, is now working on engineering artificial cardiovascular components.5

Breakthroughs in artificial organ engineering are also being made more locally. At St. Luke’s Episcopal Hospital in the Texas Medical Center, Dr. Doris Taylor is working on cultivating fully functional human hearts from proteins and stem cells. She is renowned for her discovery of “whole-organ decellularization,” a process where organs are stripped of all living cells to leave a protein framework. Taylor has successfully used this method as the first step in breathing life into artificially grown hearts of rats and pigs, and she is attempting to achieve the same results with a human heart.2

In this method, Taylor uses a pig heart as a scaffold, or protein template, for the growth of the human heart, as they are similar in size and physiological structure. In order to create such a scaffold, Taylor first strips pig hearts of all their cells, leaving behind the extracellular matrix and creating a framework free of foreign cells. The heart is then immersed for at least two days in a detergent found commonly in baby shampoo, which results in whole-organ decellularization. The decellularized pig heart emerges from the detergent bath completely white, since the red color of organs is usually derived from the now-absent hemoglobin and myoglobin (two oxygen-carrying proteins) in the cells. Therefore, only the structural proteins of the organ—devoid of both color and life—remain.2

To bring this ghost heart to life, Taylor enlists the aid of stem cells from human bone marrow, blood, and fat. The immature stem cells have the potential to differentiate into any cell in the body and stimulate the growth of the artificial organ. After the stem cells are added,2 the artificial heart is placed in a bioreactor that mimics the exact conditions necessary for growth, including a separate blood and oxygen supply as well as a beating sensation.6 Amazingly, a heartbeat is observed after just a few days, and the artificial organ can successfully pump blood after just a few weeks.2

Of course, this method is not limited to the development of a single type of organ. Not only will Taylor’s research benefit patients suffering from heart failure, it will also increase availability of other artificial organs like livers, pancreases, kidneys, and lungs. Taylor has already proven that decellularization and stem cell scaffolding is a practical possibility with other organs; additionally, she has completed successful lab trials with organ implants in rats.4 While the full growth of a human heart is still being refined and other organ experiments have recently been completed, Taylor predicts that her team will be able to approach the Food and Drug Administration (FDA) with proposals for clinical trials within the next two years. The trial of integrating entire organ into human patients may be further into the future, but Taylor proposes that they will begin with cardiac patches and valves, smaller functioning artificial portions of a heart, to show the safety and superiority of the decellularization and stem cell scaffolding process. Hopefully, after refining the procedure and proving its success, whole-organ decellularization will be used to grow organs unique to every individual who needs it.2

While this process is useful for all transplant patients, it is especially important for people with heart disease. The muscle cells of the heart, cardiomyocytes, have no regenerative capabilities.4 Not only is heart tissue incapable of regeneration, but the transplant window for hearts is also extremely short: donor hearts will typically only last four hours before they are rendered useless to the patient, which means that a heart of matching blood type and proteins must be transported to the hospital within that time period. Due to high demand and time limitations, finding compatible hearts within a reasonable distance is difficult. Though mechanical hearts are emerging as possible replacements for donor hearts, they are not perfect; use of a natural heart would be vastly superior.2 Mechanical hearts face the issue of unnatural malfunction; natural hearts, which are designed for a human body, will better “fit” the individual and can be tailored to avoid patient rejection. With the advent of biologically grown hearts, more hospitals will have access to replacement organs, increasing the patients’ options for transplant. Another critical advantage of artificially grown hearts lies in the fact that the patient may not need anti-rejection medication. The patient’s own stem cells could be used to grow the heart. The artificial tissue would then grow to have the same protein markers as the rest of the cells in the body, minimizing the chances that the organ would be rejected.2 Still, the use of stem cells could be potentially problematic, as human stem cells decrease in number and deteriorate in function over time. In this respect, stem cells from younger patients are usually desirable, so the eradication of all anti-rejection medication is not feasible in the near future.

The development of artificial organs provides a solution to issues of organ rejection, availability, compatibility, and mechanical failure. Dr. Taylor’s stem cell research also presents the possibility of improving current technologies that help patients with partially functioning hearts. Her work has the potential to grow skin grafts for burn centers and aid in dialysis treatment for liver failure in the near future.2

While other organs are not as fragile as the heart, decellularization and protein scaffolding can potentially benefit the body holistically. Similar to the heart, other organs such as the kidney are capable of healing themselves of small injuries as opposed to major ones requiring transplant and emergency care. Taylor’s research, though still very much in development, could change the future of transplant medicine across all organs.

References

  1. The Heart Foundation. http://www.theheartfoundation.org/heart-disease-facts/heart-disease-statistics/ (accessed Oct 14, 2013).
  2. Galehouse, M. Saving Lives With Help From Pigs and Cells. Houston Chronicle, Houston, Jan 23, 2013.
  3. Jacobson, R. Liver Buds Show Promise, but Growing New Organs is Still a Long Way Off. http://www.pbs.org/newshour/rundown/2013/07/liver-buds-show-promise-but-growing-new-organs-is-still-a-long-way-off.html (accessed Oct 14, 2013).
  4. Moore, Charles. Texas Heart Institute’s Dr. Doris Taylor in the Forefront of Heart Tissue Regeneration Research. http://bionews-tx.com/news/2013/07/04/texas-heart-institutes-dr-doris-taylor-in-the-forefront-of-heart-tissue-regeneration-research/ (accessed Oct 14, 2013).
  5. Naik, G. Science Fiction Comes Alive as Researchers Grow Organs in Lab. http://online.wsj.com/news/articles/SB10001424127887323699704578328251335196648 (accessed Oct 14, 2013).
  6. Suchetka, D. 'Ghost Heart,' a Framework for Growing New Human Hearts, Could Be Answer for Thousands Waiting for New Heart. http://www.cleveland.com/healthfit/index.ssf/2012/08/ghost_heart_a_framework_for_gr.html (accessed Oct 14, 2013). 

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