Friday, October 28, 2016

Creating organs - one cell at a time

A CLOSER LOOK: Ott examines one of the decellularized organs in his lab.

On any given day in the Ott Lab at the MGH a number of studies are underway. Bioreactors, each with an organ inside, are hooked to complicated networks of tubes carrying special solutions into the organ’s cellular scaffolding. This is the world of Harald Ott, MD, a thoracic surgeon who leads the lab’s activities. Ott’s hope is that one day the discovery of how to create organs for a multitude of medical benefits will emerge.

Ott’s clinical practice brought him to the field of organ regeneration. “As a physician, it can be heartbreaking to work with patients in organ failure because you realize at some point there is nothing else left for options,” says Ott. “After starting my training, I began to realize our tools to treat patients suffering from heart failure, end stage lung disease, and kidney failure are extremely limited. As we get better at treating acute diseases and injuries, more patients will develop end-stage organ failure and require innovative solutions.”

Ott and his research team are working to generate replacement tissues and organs on demand. For example, patients diagnosed with kidney or heart failure could have some of their cells harvested to engineer replacement kidneys. The impact would be two-fold: patients would not have to wait years for an organ transplant and also would not require immunosuppressants to prevent rejection.

The secret lies in the organ’s extracellular matrix. “You can think of this as scaffolding in each organ, which can be likened to a construction blueprint,” says Ott. “Cells, as the smallest living units, live in the scaffolding like people live in a building, and together they make our tissues and organs work. We base our regenerative efforts on native matrix, the original blueprint on which organs were built. We then move the old and damaged cells out, and bring the new ones in, creating a healthy organ.”

Recently, the Ott Lab has brought scaffolds to human scale, so researchers now can generate blueprints of human hearts, lungs, kidneys and extremities. The team now is working on driving human stem cells to form functional tissue on these scaffolds, and to develop transplant protocols, to prepare for clinical application. “While we are still years away, we have moved from small-scale research in animal cells to human-scale research across cells in several organ systems,” says Ott. 



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