Urethras and Bladders and Windpipes, oh my!

Weekly updates now seems like something of an optimistic assessment, so I am not going to make any more promises beyond very occasional updates, then anything above and beyond that quota is a bonus. Goalposts shifted, I'll move swiftly on to an interesting story about replacement tissue engineering that caught my eye.

This field is dedicated to developing tissues that can be implanted in individuals who suffer from tissue damage due to injuries or congenital defects. By using the individuals' own cells to create new tissues, this bypasses the issue of rejection that occurs when tissue transplanted from another individual is recognised as 'foreign' by the recipient's immune system, which goes on to attack and damage the transplanted tissue. It is hoped that this field will eventually become sufficiently sophisticated as to be able to develop complex replacement organs, providing an alternative option to waiting on the transplant list for donor organs.

NewScientist reports on the article in The Lancet concerning five injured boys who were given treatment to implant new urethras engineered using cells from their own bladders between the years 2004-2007. These engineered urethras are still functioning perfectly well six years after implantation, which lends researchers hope that the development of replacement tissues and organs stands as a viable long-term solution to a variety of medical problems. More recent developments in replacement tissue engineering research have led to the development of artificial bladders and windpipes.

In this instance, engineered urethras were built using different types of cells isolated and grown from a square centimetre of bladder tissue. This allowed the researchers to develop cultures of smooth muscle cells and epithelial cells, the two main tissues of the urethra. These cultured cells were used to coat a tube of biodegradable plastic, and left to grow so that the cells fully coated the tube in tissue. This tube was implanted in the damaged part of the urethra, using a catheter to hold the tube open whilst the urethras formed. After a month, the catheter was removed. A couple of months after that, tests revealed that the urethra was fully formed. Six years later, the engineered urethras are still perfectly functional.

Work done in the meantime has included bringing stem cell research into play. Stem cells are capable of forming many types of tissues in the body. Embryonic stem cells have the potential to form any type of tissue, though the ethical implications of such research have made the use of embryonic stem cells quite limited. Instead, researchers now focus on other stem cells found in certain locations in the body, for example the bone marrow. This approach is less controversial, though these cells are not capable of forming as many types of tissue as readily as embryonic stem cells. Another approach is to induce adult cells into a pluripotent (stem cell) state. This type of induced pluripotent stem cell has a greater ability to form different tissue types, potentially making it a viable alternative for most applications that might have called for embryonic stem cell research. One of the major hurdles of using stem cells is that our knowledge about what triggers stem cells to develop into specific tissue types is limited, meaning research is needed to understand how each, specific tissue type is developed. This has already been done for several tissue types, but arguably this approach will become much more difficult when dealing with the engineering of complex organs.

The use of bone marrow stem cells was the approach opted for in the development of an artificial windpipe for a woman with a collapsed windpipe caused by a severe tuberculosis infection (see NewScientist report). The stem cells were grown in culture, and then induced to become the cartilage cells that normally support the windpipe. In parallel to this, they took a stretch of windpipe from a deceased donor, and used detergent to strip away the cells (removing the foreign tissue that might have provoked immune rejection) leaving the structural network of collagen. This collagen was used as a scaffolding, upon which the stem cell derived cartilage cells were grown. The resulting windpipe was then successfully transplanted, giving her the ability to breathe normally again.

All in all, this field promises to yield some awe-inspiring stuff over the next few years and decades. As we continue to understand more about creating stem cells from normal cells, and how they can be made to form different types of tissue, the potential applications for therapy are legion. With any luck, this kind of treatment will be readily available well in time to stop me falling apart in old age.

Ageing backwards...

Last week Nature published the research of scientists from Harvard Medical School into the impact of telomerase reactivation on ageing in mice that were engineered to have short, dysfunctional telomeres. Amazingly, this process is able to reverse ageing in mice which are in an advanced stage of degeneration, indicating that reactivating telomerase may one day become an effective therapy to counter age-related degeneration in humans.

Telomeres are repetitive sequences of DNA on the ends of each chromosome that act as protective caps for the genetic information in the main body of the chromosome. It has long been understood that telomeres play a role in cellular ageing. The process of DNA replication leaves out the outermost edges of the telomere, reducing the length of the telomere in the new copy of the chromosome. After a certain number of cell cycles, the telomeres shorten to a critical length that prevents further cell division and the cells become senescent. In the case of the engineered mice, having short telomeres from the beginning meant that the process of cell ageing and senescence occurred more rapidly. As more cells become senescent and die off, tissues begin to atrophy and the function of organs begins to decline. This produces the degenerative effects associated with ageing

Reversing this process is a key factor in extending lifespan. The way to do this is well understood. The enzyme telomerase reverses telomere shortening by re-adding the length of DNA lost from the telomere cap during DNA replication. This allows the elongation of the telomere such that the cell does not enter senescence and can continue to divide. Until now, it was not understood how big an impact telomerase reactivation could have in an organism that was in an advanced stage of ageing. This research showed that after the reactivation of telomerase resulted in the regeneration of healthy tissue, improved organ function and an increased life span.

Though this development is remarkable, it must be taken with some caution. The activation of telomerase is a mechanism essential to the proliferation of cancerous cells. Thus, there is a balance that needs to be considered between the halting and reversing of degeneration and an increased risk of developing cancer.

An introduction

My name is Elliot Jokl and I am a first-year undergraduate Biology student at the University of York. I'm hoping this blog will act as a place where I can discuss interesting things that I come across during my lectures and tutorials, and also a place I can talk about any biology news that catches my attention. I'm aiming to have updates roughly once a week. We'll see how that goes.