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Human ear on mouse a milestone in medicine
By Tan Qiang |
September 2, 2011, Friday
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Print Edition
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THE dust has settled: Shanghai Jiao Tong University announced on August 26 that, contrary to earlier peer and media accusations, Dr Cao Yilin had not cheated in his experiments of growing human ears on the backs of mice, nor had he misused around 300 million yuan (US$47 million) of state funds allocated for his research.
While this is good news for Professor Cao, a pioneer in China's human tissue science, I would not try to delve into the details of accusations and counter accusations.
But let's be clear on at least one point: it's only normal for a scientist to spend a great amount of money and yet come up with no significant findings or no widespread clinical application.
Though it sounds like a lot of money, the 300 million yuan that supported Cao's research in the past decade is not a waste, as certain accusers have claimed. As with other researches, it is always a very long way from the initial proven feasibility to clinical trials.
Behind every new drug, billions of compounds are screened, tens of years and billions of dollars are spent. At its infant stage, regenerative medicine is a brand new field that requires seamless collaboration from biologists, medical doctors, chemists, engineers, and businessmen. Though the 300 million yuan has not generated the desired positive results, it helps prevent late comers from making the same mistakes again and should be well justified as an investment in the future.
Professor Cao's "man-made ear" on the back of a mouse was formed by seeding cattle chondrocytes on a human-ear-shaped biodegradable scaffold. For the first time, it proved the feasibility of creating large-size, irregular-shaped human tissue with cells, 3D biodegradable scaffold, and growth factors.
This proven feasibility marked the start of a new era of organ regeneration (vs organ transplant), when one could develop a spare heart or lung of his/her own in the same way as one carried around a spare tire in the back of the car.
Two technique obstructions need to be solved before this technique can be applied in the clinic widely: thoroughly understand the tissue regenerative niche and accelerated revascularization of the cell-scaffold construct after implantation.
The traditional tissue engineering technique is comprised of two separated steps: in-vitro cell-scaffold construct culture and in-vivo substitute regeneration.
As we often see in the SciFi movies, an alien or a witch or a crazy scientist immerses the living organ substitute in some magic liquid (often green in color) before putting it into the human body.
What the movies fail to tell us is that nowadays the magic liquid is not powerful enough to keep the cells functional on their own and due to the limit of nutrition diffusion, the liquid can only support a very thin layer of living cells on the surface of the organ substitute, leaving a lifeless center part with only the scaffold. After implantation, the excessive scaffold will induce the immune system to destroy the substitute.
On the other hand, it also proved to be extremely difficult, if not impossible, to create a vascular system inside the organ substitute. Your spare organ will undergo regenerative and revascularization processes, which takes a long time and it is often rejected by the immune system.
We were lucky with the ear-on-mouse, owing to the naive immunosystem of the nude mouse and the avascular nature of cartilage tissue.
To overcome these two problems, in our lab we recently pioneered a novel concept of "in-vivo bioreactor." With this technique, we create a medium perfusion inside the implanted tissue-engineered organ to support the cells living in the center part and refresh the cells and growth factors to promote the regenerative and revascularization process.
The immunoresponse is alleviated due to decreased scaffold exposal and increased tissue regenerative niche. So in the future movies, the characters will carry support pumps on their backs to keep their new lung, heart or any essential organs functioning and feed the organs with a custom-made medium as if they were feeding a baby.
The author is a thoracic surgeon and the vice-director of the cell therapy and regenerative medicine lab at the Shanghai Chest Hospital.
While this is good news for Professor Cao, a pioneer in China's human tissue science, I would not try to delve into the details of accusations and counter accusations.
But let's be clear on at least one point: it's only normal for a scientist to spend a great amount of money and yet come up with no significant findings or no widespread clinical application.
Though it sounds like a lot of money, the 300 million yuan that supported Cao's research in the past decade is not a waste, as certain accusers have claimed. As with other researches, it is always a very long way from the initial proven feasibility to clinical trials.
Behind every new drug, billions of compounds are screened, tens of years and billions of dollars are spent. At its infant stage, regenerative medicine is a brand new field that requires seamless collaboration from biologists, medical doctors, chemists, engineers, and businessmen. Though the 300 million yuan has not generated the desired positive results, it helps prevent late comers from making the same mistakes again and should be well justified as an investment in the future.
Professor Cao's "man-made ear" on the back of a mouse was formed by seeding cattle chondrocytes on a human-ear-shaped biodegradable scaffold. For the first time, it proved the feasibility of creating large-size, irregular-shaped human tissue with cells, 3D biodegradable scaffold, and growth factors.
This proven feasibility marked the start of a new era of organ regeneration (vs organ transplant), when one could develop a spare heart or lung of his/her own in the same way as one carried around a spare tire in the back of the car.
Two technique obstructions need to be solved before this technique can be applied in the clinic widely: thoroughly understand the tissue regenerative niche and accelerated revascularization of the cell-scaffold construct after implantation.
The traditional tissue engineering technique is comprised of two separated steps: in-vitro cell-scaffold construct culture and in-vivo substitute regeneration.
As we often see in the SciFi movies, an alien or a witch or a crazy scientist immerses the living organ substitute in some magic liquid (often green in color) before putting it into the human body.
What the movies fail to tell us is that nowadays the magic liquid is not powerful enough to keep the cells functional on their own and due to the limit of nutrition diffusion, the liquid can only support a very thin layer of living cells on the surface of the organ substitute, leaving a lifeless center part with only the scaffold. After implantation, the excessive scaffold will induce the immune system to destroy the substitute.
On the other hand, it also proved to be extremely difficult, if not impossible, to create a vascular system inside the organ substitute. Your spare organ will undergo regenerative and revascularization processes, which takes a long time and it is often rejected by the immune system.
We were lucky with the ear-on-mouse, owing to the naive immunosystem of the nude mouse and the avascular nature of cartilage tissue.
To overcome these two problems, in our lab we recently pioneered a novel concept of "in-vivo bioreactor." With this technique, we create a medium perfusion inside the implanted tissue-engineered organ to support the cells living in the center part and refresh the cells and growth factors to promote the regenerative and revascularization process.
The immunoresponse is alleviated due to decreased scaffold exposal and increased tissue regenerative niche. So in the future movies, the characters will carry support pumps on their backs to keep their new lung, heart or any essential organs functioning and feed the organs with a custom-made medium as if they were feeding a baby.
The author is a thoracic surgeon and the vice-director of the cell therapy and regenerative medicine lab at the Shanghai Chest Hospital.
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