Adult stem cell breakthrough

November 19, 2008 Adult stem cell breakthrough

The transplanted trachea.

(PhysOrg.com) -- The first tissue-engineered trachea (windpipe), utilising the patient's own stem cells, has been 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.

These remarkable results provide crucial new evidence that adult stem cells, combined with biologically compatible materials, can offer genuine solutions to other serious illnesses.

In particular, the successful outcome shows 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.

The pan-European team from the universities of Barcelona, Bristol, Padua and Milan report on this pioneering work in an article published early online and in an upcoming edition of The Lancet.

The loss of a normal airway is devastating, but previous attempts to replace large airways have met serious problems. The 30-year-old mother of two, suffering from collapsed airways following a severe case of TB, was hospitalised in March 2008 with acute shortness of breath rendering her unable to carry out simple domestic duties or care for her children. The only conventional option remaining was a major operation to remove her left lung which carries a risk of complications and a high mortality rate.

Based on successful laboratory work previously performed by the team, and given the urgency of the situation, it was proposed that the lower trachea and the tube to the patient's left lung (bronchus) should be replaced with a bioengineered airway based on the scaffold of a human trachea.

A seven-centimetre tracheal segment was donated by a 51-year-old transplant donor who had who had died of cerebral haemorrhage. Spain has a policy of assumed consent for organ donation. Using a new technique developed in Padua University, the trachea was decellularised over a six-week period so that no donor cells remained.

Stem cells were obtained from the recipient's own bone marrow, grown into a large population in Professor Martin Birchall's lab at the University of Bristol, and matured into cartilage cells (chondrocytes) using an adapted method originally devised for treating osteoarthritis by Professor Anthony Hollander at the University of Bristol.

The donor trachea was then seeded with chondrocytes on the outside, using a novel bioreactor which incubates cells, developed at the Politecnico di Milano, Italy, allowing them to migrate into the tissue under conditions ideal for each individual cell type. In order to replicate the lining of the trachea, epithelial cells were seeded onto the inside of the trachea using the same bioreactor.

Four days after seeding, the graft was used to replace the patient's left main bronchus. The operation was performed in June 2008 at the Hospital Clinic, Barcelona, by Professor Paolo Macchiarini of the University of Barcelona.

Professor Macchiarini, lead author on the paper, said: "We are terribly excited by these results. Just four days after transplantation the graft was almost indistinguishable from adjacent normal bronchi. After one month, a biopsy elicited local bleeding, indicating that the blood vessels had already grown back successfully".

Martin Birchall, Professor of Surgery at the University of Bristol, added: "Surgeons can now start to see and understand the very real potential for adult stem cells and tissue engineering to radically improve their ability to treat patients with serious diseases. We believe this success has proved that we are on the verge of a new age in surgical care".

Anthony Hollander, Arthritis Research Campaign Professor of Rheumatology and Tissue Engineering at the University of Bristol, concurred: "This successful treatment manifestly demonstrates the potential of adult stem cells to save lives".

The patient, Claudia Castillo, a young woman from Colombia but now living in Spain, had no complications from the operation and was discharged from hospital on the tenth post-operative day. She has remained well since and has a normal quality of life. She is able to care for her children, walk up two flights of stairs and occasionally go out dancing in the evenings.

She said: "Above all I would like to thank Dr. Macchiarini and his medical team who did the research, for the time and dedication they devoted to my case to make sure that everything turned out alright."

Provided by University of Bristol


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  • MGraser - Nov 19, 2008
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    This sounds very exciting, but I have to admit ignorance. How can you decellularise something and still have anything left? The rest of it makes sense to me. Thanks!
  • Mercury_01 - Nov 19, 2008
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    I want a new meniscus for my knee!
  • PPihkala - Nov 19, 2008
    • Rank: 5 / 5 (1)
    I think I saw an article about decellularising some time ago. I think one explanation would be to explain that normal tissue consists of two kind of cells, one's making a scaffold and then the soft tissue cells held in shape by those structure giving cells. By decellularizing one takes away those soft tissue cells and one is left with the scaffold. Then they repopulate the scaffold with the patient originated soft cells made by manipulating adult stem cells as told above. I think the scaffold left behind is immunoneutral and as such can be used even from another donor. I think the immunoproperties are dependent of sugars on surface of cells, in this case only on soft tissue cells, not on scaffold cells. I think the scaffold cells can be made of collagen. That is cells that have been differentiated to stringy shape. Somebody please correct me if I have made mistakes in my explanation.
  • superhuman - Nov 20, 2008
    • Rank: not rated yet
    Now this is a VERY serious breakthrough! (as opposed to others reported daily on this site)

    Great work!

    As PPihkala said, decellularising leaves the scaffold which was deposited by cells, it is made of "about 15 %u2013 20 incomplete C-shaped cartilaginous rings which reinforces the anterior and lateral sides of the trachea to protect and maintain the airway open."

    "Cartilage is a type of dense connective tissue. It is composed of specialized cells called chondrocytes that produce a large amount of extracellular matrix composed of collagen fibers, abundant ground substance rich in proteoglycan, and elastin fibers."

    You can remove the cells and you will still have this dense extracellular matrix which was then repopulated with patient cells.

    (quotes from wiki)
  • MGraser - Nov 20, 2008
    • Rank: not rated yet
    Thanks PPihkala and superhuman. This is outstanding! I suppose a future step would be to be able to construct the scaffold for the particular organ that would accept the soft cells from the patient, thus eliminating the need for a donor.

    Amazing...
  • morpheus2012 - Nov 20, 2008
    • Rank: 1 / 5 (1)
    another example why bush bann on stemm cells

    led to million of useless deaths in the last years

    nice job exept the 1,4 irakis killed

November 19, 2008 all stories

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