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Esophagus Tissue from Stem Cells Grown, Implanted

Pig close-up

(Mutinka, Pixabay)

13 March 2018. Replacement engineered esophagus tissue grown from stem cells was shown in tests with pigs to be a feasible alternative to transplanting pieces from other parts of the body for people with esophagus cancer. Results of the study by a team from the Mayo Clinic and the tissue engineering company Biostage Inc. that developed the technology appear in the 7 March issue of the journal Nature Scientific Reports.

Researchers led by Mayo Clinic thoracic surgeon Dennis Wigle are seeking better options for patients with advanced cancer of the esophagus needing affected parts of the organ removed. The authors cite data showing more than 500,000 people a year worldwide are diagnosed with this type of cancer, and that number is expected to rise by 140 percent over the next 10 years. For people not diagnosed until later stages of the disease or with more aggressive cancers, removal of part of the esophagus is often the only therapy. Reconstruction of the esophagus after removal is difficult, which requires transferring parts of the patient’s gastric or colon tissue, often with unsatisfactory results.

The study tested a technology devised by Biostage that grows new esophagus tissue from a person’s stem cells. Biostage, based in Holliston, Massachusetts, calls the process Cellframe that takes stem cells from a sample of person’s adipose, or fat, tissue. The stem cells are multiplied and seeded on an electrospun polyurethane scaffold or matrix. The seeded scaffold then is placed in a bioreactor for 3 to 5 days to allow replacement tissue to grow. The resulting Cellspan tissue implant is surgically reconnected in the patient, which provides natural signals for further growth and regeneration, with the scaffold later removed. In addition to esophagus, Cellspan implants are designed for replacing parts of the trachea and airways.

In the study, the researchers implanted Cellspan esophagus tissue in 8 Yucatan pigs, which have organs of about the same size and function similarly to humans. The team first took adipose tissue samples from the pigs, extracted mesenchymal, or adult stem cells, and grew replacement tissue on scaffolds about 6 centimeters in diameter to replace removed pieces of the esophagus. In the first 2 pigs to receive replacement tissue implants, the esophagus narrowed abnormally, that required euthanizing the animals. The next 6 implants added stents to hold the esophagus open after implantation. After 3 weeks, the scaffolds were readily removed from the remaining pigs with an endoscope-attached forceps, and no infections or foreign-body reactions reported.

The team reported growth of new esophagus tissue in the pigs, including mucous membranes, smooth muscles, and blood vessels. After 6 months, the stents holding open the esophagus implants were removed, allowing the new tissue to function on its own. At the time of reporting, 2 of the pigs were still alive after 18 and 19 months following the implants. The authors conclude engineered esophagus tissue grown from stem cells may be a feasible alternative to replacements with parts of the gastrointestinal tract.

While Cellspan implants have not yet been tested in clinical trials, in February a patient with cancer of the esophagus was implanted with replacement tissue grown from his stem cells. The Worcester (Mass.) Business Journal reports the implant was successful, but the patient later died from a stroke, apparently unrelated to the implant.

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