Release date: 2015-06-18
Guess what is the object in the picture above? This looks like a cut mouse paw, but the correct answer may be more exciting than you think: the rat's forelimb is actually used by scientists in the lab. Artificial products cultivated by living cells. Although not perfect, this technology may help people develop prosthetic limbs with real biological functions in the future.
“We are currently focusing our research on the forearms and palms for the establishment of model systems and validation of the underlying principles.†Harald Ott of the Massachusetts General Hospital in Boston is cultivating the rat. One of the main heroes of the forelimbs. “However, the same technique can be applied to other limbs such as the legs and arms.â€
"It's like a real-life science fiction novel," said Daniel Weiss of the University of Vermont Medical School, who is studying the regeneration of the lungs. “This is an exciting new technology, but how to make a fully functional limb will be a challenge.â€
Many of the prostheses installed on patients who have undergone amputation have no problem in appearance, but they cannot function like real limbs. Now, there are some artificial prostheses that use bionics on the market. They can function, but the unnatural appearance is still a bad injury. Hand transplant surgery is another solution. There are also many successful cases. However, in order to prevent rejection of the body, patients undergoing transplantation also need to take immunosuppressive drugs for life.
Once the biological limb (biolimb) is successful, many of the above problems will be solved. This limb is "cultured" by the patient's own cells, so it does not require the aid of immunosuppressive drugs, and it will be very close to the natural state of the body in terms of appearance and motor function.
"This is the first attempt at the cultivation of biological limbs, and as far as I know, there are no other technically cultivated composite organizations that can reach our complexity," Ott said.
How to make a forelimb?
The technique for making this rat forelimb is called "decal/recel" (abbreviation for decellularization and recellularization, meaning "decellularization" and "recellularization", respectively). This technique has been used in the laboratory before. Develop artificial hearts, lungs and kidneys. Some simple organs made with this technique, such as the trachea and vocal cords, have been used for transplant surgery and have been successful to varying degrees. However, it also suffered some criticism.
The first step in an artificial organ is “decellularizationâ€: the donor's organs/limbs are treated with detergent, stripping off all the soft tissue, leaving only the organ “stent†made up of inert collagen, so that it remains intact Their original complex structure. In this experiment of culturing rat forelimbs, the collagen structure at the blood vessels, tendons, muscles and bones was retained after this step.
The second step is “recellularizationâ€. At this time, the cells that receive the transplanted individual are “planted†on the “organ scaffoldâ€, and then they are cultured in a bioreactor, and the new tissue cells are attached to the scaffold. Eventually, the organ will be restored to a state of "blood and flesh". Eventually, the new organ will not leave any soft tissue with donor cell characteristics, so it will not be recognized as an "exotic" by the recipient's immune tissue. In this way, the rejection reaction can be avoided.
Also using the method of decellularization and re-culture, creating a forearm is much more difficult than culturing the trachea because the former needs to cultivate more types of cells. In order to solve this problem, Ott first placed the decellularized rat forearm "skeleton" in the bioreactor and provided nutrients, oxygen and electrical stimulation with a manual circulation device. Subsequently, he injected human endothelial cells into the collagen scaffold of the blood vessel, and after 1 hour, the endothelial cells reattached to the surface of the blood vessel. This step is very critical, he said, because it will make the new growing blood vessels more robust, without cracking in the presence of liquid circulation.
Next, he mixed mouse myoblasts, mouse embryonic fibroblasts, and human endothelial cells into a vacancy in the forelimb scaffold that was originally occupied by muscle tissue. After 2 to 3 weeks, the reconstruction of blood vessels and muscles is completed. Finally, Otto performed a skin transplant on the forelimbs and finally finished.
However, can the muscles of this forelimb be used? To verify this, the team used electrical impulses to stimulate the muscles and found that the paws of the rats really made a grip, and the mandatory tension of the muscles reached the muscles of the newborn rats. 80%. "This shows that we can achieve the bending and stretching of the palm," Ott said. They also performed transplants on several rats and actually tested the efficacy of this biological limb. After the vascular connection is completed, the blood of the recipient rat smoothly flows into the blood vessels of the artificial forelimb, and the pulsation of the blood flow can be recorded. However, they did not test muscle motor function or rejection in living rats.
Long road ahead
Ott said that although they have completed the decellularization of the forelimbs of nearly 100 rats, and at least half of them have been "planted" with new cells, there is still much work to be done. First, they need to plant cells in the limbs that make up other tissues such as hard bones and cartilage to see if they can regenerate. Next, they must prove that the nervous system can also complete the reconstruction. The results of previous hand transplant surgery showed that the nerve tissue of the recipient can extend and penetrate the newly connected palm, and finally realize the control of the new organ. Whether artificially implanted biological limbs can also do this step remains to be verified by further experiments.
In addition, Ott and colleagues also demonstrated the successful decellularization of the primate forearm (see figure below). At present, his team has begun to cultivate human vascular cells on the "stent" of primates, which is the first step to human limb technology. At the same time, they also began to replace mouse myoblasts with human myoblasts in a rat test and observed the effect. However, Ott pointed out that a large amount of follow-up work is indispensable, and we need to wait at least 10 years before the emergence of biological limbs that meet human testing requirements.
"This is a remarkable development and has a solid scientific foundation. However, Harald's team still needs to solve some technical problems." Steven Badylak of the University of Pittsburgh, Pennsylvania The commentary said that he had implanted the implant on a scaffold made of porcine muscle tissue and successfully regenerated the damaged muscle of the leg in 13 patients. "In all of these problems, blood circulation is probably the toughest, and you have to make sure that endothelial cells cover the smallest capillaries so they don't collapse and cause blood clots," he said. "But it will already It is actually an engineering problem to know the basic principles of biology and put it into practice. Engineers do just that."
Other researchers have put forward more criticism. "For a complex organ like a hand, there are so many organizations and structures, so this method is certainly unrealistic." Oskar Aszmann of the University of Vienna in Austria said that he had invented A bionic hand that can be controlled with "ideas". “And, in order for a hand to achieve meaningful function, it must be filled with thousands of nerves, which is still an insurmountable difficulty. So, although this is a very valuable Work, but it can only stay at the basic research stage and cannot enter clinical practice."
Ott envisions that in the future, human organ donation programs may also include limb donations. Cells for regenerating blood vessels can be obtained from small blood vessels of the recipient, while muscle cells can be obtained from large muscles such as the thigh. "If you extract about 5 grams of muscle tissue, you can grow human skeletal muscle myoblasts."
There are 1.5 million amputees in the United States alone, so this limb regeneration study is of great significance, says Ott. "At present, if you lose your arms and legs, or if you have damaged some soft tissue because of cancer treatment, burns, etc., the treatment options you can choose are very limited."
Source: Shell Network
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