Regenerating tissue through autologous cells: a personal appeal

The trachea is one of the most challenging organs to transplant, with a high risk of necrosis and infection due to inadequate graft revascularization and the fact that it's constantly exposed to airborne elements. Transplants requires lifelong immunosuppression, which also carry high risks. Prosthesis can rupture, generate infection, and cause injury.

What to do then? One answer is tissue engineering.

Dr. Paolo Macchiarini is one of the pioneers in this techniques. In a recent paper [1] he and his co-authors

"describe in detail the tissue engineering approach used for tracheal construction, with a focus on the mobilization, isolation, and in vitro culture of cell types with high potential for use in bioengineering."

The technique is highly sophisticated and I'm sure I'm doing a poor job here in trying to explain it in simple terms. The starting point is a scaffold that should provide the basic characteristics of the trachea. As Macchiarini and colleagues state in the paper,

"Despite intensive research in this field, no solution has been proposed as being optimal; currently both natural and synthetic grafts are being used."

In one case study in particular, they used as scaffold a decellularized cadaveric organ from a human donor trachea, and then colonized it by epithelial cells and MSC-derived chondrocytes cultured from autologous cells taken from the patient. They aspirated bone marrow from the patient to obtain marrow mononuclear cells. These contain a class of repair cells called multipotent mesenchymal stem/progenitor cells, cells that are able to differentiate and hence can be used to regenerate tissue. The researchers separated the cells, differentiated them, and then seeded them along a scaffold:

"We then expanded and differentiated these cells toward chondrocytes and seeded the cells into the exterior spongy layer of the scaffold, where they formed the cartilaginous component. For generating the inner epithelial lining of the trachea, we seeded the surface of the scaffold with nasal epithelial cells, after in vitro expansion to obtain sufficient numbers for seeding the graft."

Above: The entire concept of the regenerative approach to tracheal transplantation using natural scaffolds. MNC, mononuclear cell.

While ex-vivo, the tissue is maintained through a perfusion system called bioreactor. Once implanted, several pharmacologic intervention are prescribed to minimize the risk of necrosis, infection, and cell migration. Despite the non-trivial risks, the result is incredible:

"Since 2008, nine patients (ranging in age from 11 to 73 years), with either benign or malignant conditions, were treated using this decellularized scaffold. To date, the new in vivo engineered transplanted tracheas have been shown to be viable and to possess a good epithelial coating, are characterized by immediate vascularization, and, above all, maintain a constantly open lumen for air passage."

Please help Rachel Breathe

Now, to most of us, what I've discussed above is fascinating science. To some, is hope for a new life. Rachel Phillips was a ballet dancer with Royal Ballet in London, the Kirov in St. Petersburg, Russia and other major companies in the US and abroad. Today, with over 90% of her airways collapsed, Rachel is fighting for her life. She suffers from a genetic disorder called Ehlers–Danlos syndrome, which is caused by mutations in a number of genes involved in either the structure, the production, or the processing of collagen. Collagen is essential in all connective tissues in the body. Because of this Rachel needs a new trachea and Dr. Macchiarini's tissue regeneration technique can give her one but she needs our help.

Please visit Rachel's website at helprachelbreathe.com/ and help her out with a donation. This is not just science. It's life!

Thank you.

[1] Jungebluth, P., Moll, G., Baiguera, S., & Macchiarini, P. (2011). Tissue-Engineered Airway: A Regenerative Solution Clinical Pharmacology & Therapeutics, 91 (1), 81-93 DOI: 10.1038/clpt.2011.270