Anthony Atala, director of the Wake Forest Institute for Regenerative
Medicine, presented a riveting TED talk in October 2009 (broadcasted
January 2010) about organ regeneration. Atala initially lays out the
current dilemma with organ transplantation: although the demand for
donor organs has multiplied several-fold over the years, the annual rate of transplantation has remained virtually unchanged due to a limited supply of organs. Atala adds, “Every 30 seconds, a patient dies from diseases that could be treated with tissue replacement.” His answer to the supply bottleneck? … grow “artificial” in the laboratory.
In 1996, natural biomaterials were used as a “bridge” to promote cell
growth and repair in a damaged urethral tube. This technology was
however limited by a maximum wound length (approximately 1 cm) where
the cells would regenerate. What about larger injuries? Atala provides the example of a bio-reactor strategy used to create a carotid artery. First, myocytes are grown in vitro and “exercised” using a linear oscillating device to develop muscle strands that are acclimated to contractile motion. These cells are then coated along a biodegradable tubular scaffold and incubated at 37 oC and 95% oxygen concentration to approximate the thermodynamics inside the human body. The internal wall of the tubular scaffold is coated with vascular endothelial cells. The end-product is a vascular vessel with external muscular and internal endothelial walls.
Similar principles can be applied to more complex organs. The Wake
Forest Institute for Regenerative Medicine has also been successful at
creating a bladder using an ovoid scaffold overlaid by human cells and
growth media. The process takes about 6-8 weeks for each
“manufactured” bladder. Atala adds that the Institute can also create
bladders of different sizes, joking that his attentive audience at the TED talk would probably prefer the XL version. Other organs produced by the Institute include heart valves, ears, and digits.
The next steps of active research involve the growth of significantly
more complex and highly-vascularized organs, such as the heart, liver,
and kidney. One project under study is the use of a modified desktop
inkjet printer to “print” solid organs through systematic layering of
cells. Another technique is to form new organs from autologous cells
using the collagen/vasculature infrastructure of donor organs. Mild
detergents are first used to remove the donor organ’s cell elements,
leaving a “skeleton” of collagen and retained vasculature. The organ
is then perfused and coated with the patient’s own cells. This concept
is interesting in that it would increase the supply of donor organs by
permitting the use of dysfunctional, but structurally preserved,
organs. Moreover, the use of autologous cells would theoretically
decrease the risk for rejection.
Although Atala was able to distill his talk to less than 20 minutes,
the immense resources invested into this research effort are by no
means diminutive. There have been 700 researchers over the past 20
years at the Wake Forest Institute for Regenerative Medicine and its
collaborating sites working on organ regeneration. The potential
impact of this research effort is similarly staggering, particularly
for the thousands of patients and their families who eagerly await the
phone call that an organ is available. On a more personal note, my first
patient to die during my residency training was on the liver transplant list, but unfortunately did not survive long enough to receive a replacement organ. While I cannot imagine the emotional duress his family endured, the event was painful for me as well. I eagerly look forward to the many advances stem cell and organ regeneration research may bring … as well as the countless lives they may save.
