Last week, we discussed the amazing case of the hydra, a small “pond scum” that can live forever.  You can also cut it in half and it can grow back the identical part!

If you missed the video by Robert Krulwich, you’ve got to watch it! Here it is again:

We asked two questions: How could the hydra live forever? (the answer is “cellular garbage disposal”) And how can it regenerate its missing parts? (which we left unanswered until now). So here it is.

The hydra is made up of cells that can get activated to divide at the drop of a hat and form the missing tissue.  Such cells are called stem cells. They constitute a small portion of every tissue and constantly divide to form new cells to replace the senescent ones. So, an important question for us is:  Since we have stem cells, just like the hydra, why can’t we regenerate an amputated arm, or a damaged heart?

Well, yes, we can!

Up to a point, that is.

If you ever visit Israel, don’t miss the most ancient port of civilization: Jaffa. There, in the sea, about 100 feet from the water’s edge you will see a big rock. According to Greek mythology, Andromeda was chained to this rock by a sea monster as punishment for the hubris of her mother Cassiopeia, Queen of Ethiopia.

She was visited daily by an eagle that would pick at her and eat part of her liver (Yikes!), but during the night the liver would grow back to it original shape and size. (In case you feel sorry for her, don’t. She was rescued by Perseus who promptly married her. As a consolation prize for her troubles, she and her mother had heavenly constellations named after them. Beat that, Hollywood!). Aside from the romantically gruesome story, this must be the earliest instance of organ regeneration. Those smart Greeks already knew what we rediscovered centuries later: the liver can be damaged or resected to one third of its original size and it will regrow back, although a lot slower than in ancient times.

But good luck regenerating a damaged part of the heart. Or what about an amputated leg? or a simple skin wound? The healing wound will not form the beautiful smooth skin you’ve had before your unfortunate collision with an immovable object – it will form a scar, sometimes an ugly one. So will the damaged heart, or kidney, or the brain. One can understand the rationale: waiting for a big gaping wound to regenerate the original tissue takes time. In the meantime you are incapacitated, which in nature means lunch for the hyena, the lion or the vulture. Time is of the essence, and scar tissue forms relatively fast. We still don’t know why the liver will regenerate in response to surgical (or eagle) “amputation” but will form a scar (liver fibrosis, aka liver cirrhosis) in response to alcohol or diabetes or a virus. Be that as it may, the bottom line is that the stem cells are somewhat inhibited from performing their duty.

How do we get around this problem? Enter Regenerative Medicine.

There are several approaches to regaining our capacity to regenerate, all coming under the rubric of regenerative medicineWhat that means is the branch of medical science that deals with the process of replacing, engineering or regenerating human cells, tissues or organs to restore or establish normal function. Please note: regenerating not only an organ, but a fully functional one.

In a previous post, we described one approach: to reactivate existing, but dormant, stem cells. Skeletal muscles, and apparently cardiac muscles as well, can regain their youthful appearance and function by exposing them to protein factor, GDF11, that circulates in young blood but declines with age. The hormone oxytocin, whose concentration in blood also declines with age, is another candidate as a rejuvenation factor. Factors inhibiting stem cell function were identified in concentrations that rise with age; removal of such factors to unleash stem cells to their full potential is another promising avenue of research.

Tissue engineering

Tissue engineered trachea
Tissue engineered trachea

In June 2008, the first tissue-engineered trachea (windpipe), utilizing the patient’s own stem cells, was successfully transplanted into a young woman with a failing airway. The bioengineered trachea immediately provided the patient with a normally functioning airway, thereby saving her life. The successful outcome showed it is possible to produce a tissue-engineered airway with mechanical properties that permit normal breathing and which is free from the risks of rejection seen with conventional transplanted organs. The patient has not developed antibodies to her graft, despite not taking any immunosuppressive drugs. Lung function tests performed two months after the operation were all at the better end of the normal range for a young woman.

Scientifically, this was a huge breakthrough. But how many patients need a trachea transplant? Not very many. But the same technique is now applicable to formation of new cartilage. Now we are talking massive numbers: An estimated 52.5 million adults in the United States reported being told by a doctor that they have some form of arthritis, rheumatoid arthritis, gout, lupus, or fibromyalgia.

How about another affliction of old age? Few people are aware that macular degeneration is an incurable eye disease and that it is the leading cause of vision loss for those aged 55 and older in the United States, affecting more than 10 million Americans. It’s a terrible affliction – and the research into the causes and treatment of this dread disease has been basically stymied.

A lot tantalizing clues pointing to inflammatory factors, meticulous anatomical measurements of affected retinas, but no real breakthrough. So are we doomed to wait until that happens? Can we make an end run around the difficulties? Here is a ray of hope: On Sep 12, 2014, surgeons at the Institute of Biomedical Research and Innovation Hospital in Kobe, Japan, transplanted a 1.3 by 3.0 millimeter sheet of retinal pigment epithelium cells, which were differentiated from induced pigment epithelium cells (stem cells induced to proliferate) into an eye of an elderly woman, who suffers from age-related macular degeneration.

What else is in the pipeline?

The lowly skin wound isn’t trivial at all when it comes to burn wounds – they are grossly disfiguring. In January 2014 Swiss bioengineers reported that people who need skin grafts because of burns or other injuries might someday get lab-grown, bioengineered skin that works much like real human skin.

This new skin not only has its own blood vessels but also — and just as important — its own lymphatic vessels. The lymph vessels are needed to prevent the accumulation of fluids that can kill the graft before it has time to become part of the patient’s own skin, the researchers said. This is important because all organs in the human body — with the exception of the brain and inner ear — contain lymph vessels. Until now lack of lymphatic drainage was a major obstacle to the viability of other bioengineered organs. It opens the way to bioengineered hearts, kidneys, liver, blood vessels, etc.

I think this one takes the prize: the thymus gland is the “school” where lymphocytes get their education to recognize foreign from self. This is the basic function of the immune response, without which we succumb to infection and cancer. And indeed, starting at middle age the thymus progressively shrinks in size and loses its function. So wouldn’t it be incredible if we could keep our thymus forever young?

In September 2014, scientists reported reprogramming cells inside a mouse and growing those cells into a fully functioning thymus gland. To grow the thymus gland, the scientists started with a group of cells from a mouse embryo called fibroblasts, and then increased the levels of a particular protein responsible for developing the thymus gland. The cells grew into a thymus that had the same structure and function of one that grew on its own. It was also able to produce T lymphocytes, cells that fight infection and cancer cells.

So with this avalanche of exciting new discoveries, can one resist a bit of “irrational exuberance”? At this un-optimistic juncture of the human story, we deserve a bit of an uplift.

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.

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