The State Of Regenerative Medicine 20 Years After ‘Earmouse’

It’s been 20 years since the appearance of earmouse, how far has regenerative medicine come since then?

AsianScientist (Nov. 30, 2015) – For those of you old enough to be alive at the time, think back to what you were doing in 1995. You might remember Mariah Carey singing about her “sweet, sweet fantasy baby” on the radio, and the most tech-savvy among you might have been checking out a new-fangled auction website on your brand new copy of Windows 95.

Professor Charles Vacanti, on the other hand, was busy growing what appeared to be a human ear on the back of a hairless mouse.

In actual fact, the ‘ear’ was cow cartilage tissue that had been grown over a biodegradable polymer scaffold and contained no human cells. The wrinkly, hairless mouse—which overwrought detractors claimed to be genetically modified—was simply from a strain of mice that had a spontaneous mutation which left them with a weakened immune system. Known to scientists as a ‘nude’ mice, their lack of an immune system prevented transplant rejection, allowing the foreign cow cells to grow.

Intended to be a proof-of-concept and never transplanted onto the three-year-old girl whose ear it was modeled after, earmouse nonetheless became a lightning rod for controversy. But it also hinted at the promise of regenerative medicine: the untold ability to generate new body parts at will.

Still more exciting advances were about to come. In the same year that Vacanti published his paper describing earmouse, the world was introduced to Dolly the sheep, the very first mammal to be cloned.

Hype and hyperbole

Since then, scientists have waxed lyrical over the potential of stem cells. With the ability to grow into any cell in the body, stem cells—in theory—could provide humankind with much needed organs for transplantation and the option of renewing worn out body parts as we age.

So why aren’t replacement organs something you can simply buy off the shelf by now, a full two decades after earmouse? After all, stem cells should be a mature technology by now, and haven’t discoveries like induced-pluripotent stem (iPS) cells made it easier than ever to get as many stem cells as you scientists need? And while we’re at it, why haven’t you cured cancer?! [Short answer to the last one: please read this.]

Well, it isn’t so simple; let me try to explain.

Cell –> Tissue –> Organ

Getting stem cells is only the first step. If you somehow managed to get a hold of your own stem cells and injected them into your body, you would not get youthful, radiant skin, but you might develop bone tissue in your eyelids or a nasty looking tumor called a teratoma [Google at your own risk!].

Before they can be safely used, stem cells have to be guided down the path of differentiation into the right type of cell. Thankfully, scientists have this part quite well figured out, and have created cartilage cells and liver and pancreatic precursors, among other types of cells. Last year, scientists even used iPS cells that had been differentiated into retinal pigment epithelial cells to treat a 70-year-old woman with age-related macular degeneration, marking the first use of iPS-derived cells in humans.

But in most other cases, a few million cells in a dish does not a functioning organ make. The next challenge is to coax the two-dimensional dish of cells to organize themselves into three-dimensional, fully functioning organs. As it turns out, this is much more difficult for organs like kidneys and hearts than simpler bits of cartilaginous tissue like ears; to say nothing of complex organs like eyes and brains.

Nonetheless, even here scientists have made progress. One strategy is to use organs that have been stripped of their cells as a scaffold, and then coaxing the patient’s cells grow to onto them. Alternatively, biocompatible 3D-printed scaffolds have been used, in this case to create mini-kidneys.

The vascularization challenge

Sounds pretty encouraging right? But one considerable challenge remains: vascularization, or hooking up the lab-grown organs into the patient’s circulatory system. All organs, lab-grown or not, need oxygen and nutrients from the blood to survive. Kidneys, in particular, present a unique challenge as their function depends on a fine network of capillaries which help to filter out waste products and excess water.

Because of the difficulty of growing suitable blood vessels along with the desired organ, researchers have thus far only been able to produce mini-organs, or organoids. These resemble their full-sized counterparts and can function in a similar way, but are too small to be used in human transplants for the moment. They are useful, nonetheless, for testing how different organs might respond to new drugs and could thus speed up drug discovery.

But for the thousands of people on a waiting list for a new heart or kidney, organoids just won’t cut it. Thankfully, two recently published papers suggest that the wait might not be another 20 years.

In the first study, researchers at Kumamoto University showed how human iPS-derived kidney tissue could successfully connect to the capillaries of the mouse host used, a prerequisite for a functioning kidney. Even more impressively, the authors of the second study demonstrated something similar in pigs, a much larger organism with a biology more similar to that of humans. Their system was able to generate urine, and was even successfully connected to the bladder.

This is of course not to say that made-to-order kidneys will be available next year. Many steps and precautions remain before this technology can be made mainstream. However, as I hope I have conveyed, be rest assured that scientists are not sitting around twiddling their thumbs but are actively tackling each challenge along the way.

The promise of regenerative medicine is being actualized, but scientists need time. Vacanti himself predicted in 1998 that we would need at least another 20 to 30 years, so give us at least another ten years!

This article is from a monthly column called From The Editor’s Desk(top). Click here to see the other articles in this series.


Copyright: Asian Scientist Magazine; Photo: Imgflip.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Rebecca did her PhD at the National University of Singapore where she studied how macrophages integrate multiple signals from the toll-like receptor system. She was formerly the editor-in-chief of Asian Scientist Magazine.

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