Coaxing “Master” Cells to Repair Disease

 

 

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The great promise of regenerative medicine is that one day, a person’s body may be able to heal itself—whether it is by producing insulin to cure diabetes, new beating cells for an ailing heart, or spinal cord cells that can heal themselves after a trauma.

A smattering of laboratories within GUMC are focused on unique approaches to this type of medicine—by stimulating stem cells that already exist within the body, or by removing adult cells and manipulating them to become progenitor or “stem-like” cells that are just a step or two more advanced than embryonic stem cells in their development.

GUMC adult stem cell research, some of which had been ongoing for some time, took a new focus in 2007 when a group of researchers, including Father Kevin FitzGerald, SJ, PhD, a Jesuit priest, research associate professor, and David Lauler Chair for Catholic Health Care Ethics, and G. Ian Gallicano, PhD, associate professor in the Department of Biochemistry and Molecular & Cellular Biology, worked together with Howard University to set up a program that would use adult stem cells to help treat sickle cell anemia.

And there are other projects, as well: Martin Dym, PhD, a professor in the Department of Biochemistry and Molecular & Cellular Biology, has demonstrated how, using a relatively simple laboratory technique, testes cells from adult men can be removed and safely coaxed back into more primitive and powerful cells, which are then potentially capable of morphing into any tissue type a body needs.

“Given these advances, and with further validation, it is possible that in the not–too-distant-future, men could be cured of disease with a biopsy of their own testes,” he says. The study used testes biopsies from organ donors to prove the point, but taking a biopsy of the testes is a common procedure when men are suspected of having testicular cancer, he says.

The idea with this approach is that adult stem cells in the testes would be harvested from men with an incurable disorder or disease and then grown in the laboratory with a cocktail of chemicals and growth factors. This causes the cells to revert back into a pluripotent state, which could then be driven into chosen cell types. Nady Golestaneh, PhD, research assistant professor and the first author of the paper “Pluripotent Stem Cells Derived from Adult Human Testes,” is investigating the capacity of these cells to differentiate into retinal progenitor cells.  The long-term goal is to treat retinal degeneration, the leading cause of blindness in the United States. She recently received an NIH grant to pursue her work.

If cells removed from the body can be coaxed back into a stem-like state, why not just do the same to cells already in the body, asks Jean R. Wrathall, PhD, director of the Center for Neural Injury and Recovery.

She is working toward a day when patients with spinal cord injury (SCI) will be able – with the assistance of a few stimulating molecules – to “self repair” their damaged nerves.

What often happens in SCI is that the long axons of neurons that stretch from the brain to the spinal cord remain alive, while their insulating myelin sheath, made by cells called oligodendrocytes, is damaged so that signals can’t be sent along the nerves.

But Wrathall says some recovery is seen in people with these injuries. “A regenerative process is started, new blood vessels are made, cells start dividing, and some remyelination happens – but it is not enough.”

She has found evidence of extensive proliferation of oligodendrocyte progenitors and possibly stem cells around sites of injury, and the question she is asking is whether it is possible to add chemical signals to selectively stimulate these cells – already in the body - into repairing the spinal cord.

Gallicano’s work centers on understanding the signals that direct stem cells to become all of the different kinds of cells that make up the body, but he also performs a watchdog role, of sorts, over the field. Some of the initial problems seen in successfully pushing adult cells, such as from the skin, to become stem cells, have been solved, but some issues still remain, he says. “For example, when you revert cells back into an embryonic-stem like state, they inevitably create cancers known as teratomas, which come from germline-tissue,” he says. These tumors are sometimes seen in female ovaries and male testis, where they can grow teeth and hair, but, more commonly, are often seen when adult cells in the laboratory are pushed back to become embryonic stem-like cells.

“The problem is that in their new environment, they don’t have the right three-dimensional structure or signals to tell them to stop growing and differentiating into different cell and tissue types,” he says. “If you put embryonic stem-like cells into the heart, they can “connect” electrically with the heart; however, there is a marked risk that some cells could potentially grow teeth.

“Adult stem cells, on the other hand, do not form teratomas; however, they also don’t connect electrically with the rest of the heart and, as a result, can create arrhythmias.

“In working with adult stem cells, I am looking at quality control in use of all of these kinds of cells,” Gallicano says. “In order for the FDA to say we can use these cells, we have to know exactly what they are going to do, and what can go wrong – just like we study the use of any drug.”

As a Catholic, Jesuit institution, Georgetown University abides by the Ethical and Religious Directives for Health Care, which serve as the Catholic Church’s guidelines for research and clinical care in a health care setting.

And FitzGerald is a member of the Pontifical Academy for Life, a group that advises Pope Benedict XVI, which has been especially involved in the Church’s deliberations on the issue of the future of stem cells for therapy.

FitzGerald agrees that scientists studying regenerative medicine should be very cautious. “We are not at the point where this kind of therapy is imminent, but there have been incredible advances of late, progress we have been told in the past would not be possible,” he says. “These cells may offer more of a capacity for treatment than we ever imagined.”

By Renee Twombly, GUMC Communications