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由自体干细胞培育静脉血管移植获得成功

已有 4070 次阅读 2012-6-15 10:13 |个人分类:学术园地|系统分类:论文交流

     《柳叶刀》杂志6月14日发表一项研究报道,瑞典科研人员用来自患有肝外门静脉阻塞10岁女孩骨髓干细胞培育出静脉血管,并成功地将静脉血管移植给该患儿,使患儿门静脉循环得以恢复。 由于移植物源自自身细胞,患儿术后无需服用免疫抑制剂。下面是论文摘要和美联社有关的报道。

论文摘要

Transplantation of an allogeneic vein bioengineered with autologous stem cells: a proof-of-concept study

Background
Extrahepatic portal vein obstruction can have severe health consequences. Variceal bleeding associated with this disorder causes upper gastrointestinal bleeding, leading to substantial morbidity and mortality. We report the clinical transplantation of a deceased donor iliac vein graft repopulated with recipient autologous stem cells in a patient with extrahepatic portal vein obstruction.
Methods
A 10 year old girl with extrahepatic portal vein obstruction was admitted to the Sahlgrenska University Hospital in Gothenburg, Sweden, for a bypass procedure between the superior mesenteric vein and the intrahepatic left portal vein (meso Rex bypass). A 9 cm segment of allogeneic donor iliac vein was decellularised and subsequently recellularised with endothelial and smooth muscle cells differentiated from stem cells obtained from the bone marrow of the recipient. This graft was used because the patient's umbilical vein was not suitable and other strategies (eg, liver transplantation) require lifelong immunosuppression.
Fiindings
The graft immediately provided the recipient with a functional blood supply (25—30 cm/s in the portal vein and 40 mL/s in the artery was measured intraoperatively and confirmed with ultrasound). The patient had normal laboratory values for 9 months. However, at 1 year the blood flow was low and, on exploration, the shunt was patent but too narrow due to mechanical obstruction of tissue in the mesocolon. Once the tissue causing the compression was removed the graft dilated. We therefore used a second stem-cell populated vein graft to lengthen the previous graft. After this second operation, the portal pressure was reduced from 20 mm Hg to 13 mm Hg and blood flow was 25—40 cm/s in the portal vein. With restored portal circulation the patient has substantially improved physical and mental function and growth. The patient has no anti-endothelial cell antibodies and is receiving no immunosuppressive drugs.
Interpretation
An acellularised deceased donor vein graft recellularised with autologous stem cells can be considered for patients in need of vascular vein shunts without the need for immunosuppression.
Funding
Swedish Government.
 
 
Vein grown from girl's own stem cells transplanted
 
The Associated Press 
 
Posted: Jun 14, 2012 10:37 AM ET
 
Last Updated: Jun 14, 2012 10:36 AM
 

For the first time doctors have successfully transplanted a vein grown with a patient's own stem cells, another example of scientists producing human body parts in the lab.

In this case, the patient was a 10-year-old girl in Sweden who was suffering from a severe vein blockage to her liver. Last March, the girl's doctors decided to make her a new blood vessel to bypass the blocked vein instead of using one of her own or considering a liver transplant.

They took a 9-centimetre section of vein from a deceased donor, which was stripped of all its cells, leaving just a hollow tube. Using stem cells from the girl's bone marrow, scientists grew millions of cells to cover the vein, a process that took about two weeks. The new blood vessel was then transplanted into the patient.

Because the procedure used her own cells, the girl did not have to take any drugs to stop her immune system from attacking the new vein, as is usually the case in transplants involving donor tissue.

"This is the future for tissue engineering, where we can make tailor-made organs for patients," said Suchitra Sumitran-Holgersson of the University of Gothenburg, one of the study's authors.

She and colleagues published the results of their work online Thursday in the British medical journal Lancet. The work was paid for by the Swedish government.

The science is still preliminary and one year after the vein was transplanted, it needed to be replaced with another lab-grown vein when doctors noticed the blood flow had dropped. Experts from University College London raised questions in an accompanying commentary about how cost-effective the procedure might be, citing "acute pressures" on health systems that might make these treatments impractical for many patients.

Sumitran-Holgersson estimated the cost at between $6,000 and $10,000.

Similar methods have already been used to make new windpipes and urethras for patients. Doctors in Poland have also made blood vessels grown from donated skin cells for dialysis patients.

Patients with the girl's condition are usually treated with a vein transplant from their own leg, a donated vein, or a liver transplant. Those options can be complicated in children and using a donated vein or liver also requires taking anti-rejection medicines.

Since her first transplant, the girl has grown 6 centimetres and gained weight. Her parents say she is much more focused, articulate and physically active, Sumitran-Holgersson said. The girl was not identified.

"She was always tired and hardly went to school before," Sumitran-Holgersson said. "Last week, her father said she did somersaults for the first time."

Other experts predicted it should soon be possible for doctors to build things like blood vessels and arteries for patients.

"For simple structures like veins, this technology is definitely feasible," said Dr. Anthony Atala, director of the Institute for Regenerative Medicine at Wake Forest Baptist Medical Center. He was not part of the Lancet study. "This is a strategy that shows blood vessels can be engineered and then used anywhere in the body."

Atala said lab-made veins could be used for conditions including dialysis and heart surgery. However, he said patients who get such veins need to be followed for years to make sure there aren't any serious side effects or complications.

Dr. Laura Niklason, vice-chair of anesthesiology and biomedical engineering at Yale University, said it might be more challenging to replace arteries elsewhere in the body, including near the heart, where the blood pressure is higher and the structure would be under more strain.

But she said getting organs made in laboratories was no longer science fiction. While producing complicated things like kidneys, lungs and livers might take a bit longer, other body parts — like engineered skin and cartilage — are already widely available.

There are several experiments under way for blood vessels, similar to the Lancet study.

"This type of thing is not 20 years away," Niklason said, estimating that more patients might get lab-made vessels in about five years.

 

 



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