Multipotent stem cell treatments offer promise in many diseases

Regenerative medicine that uses multipotent stem cells holds promising treatment options for many diseases, according to a speaker at the Exponential Medicine conference in San Diego.

Alan Russell, PhD, director of the Disruptive Health Technology Institute at Carnegie Mellon University, told attendees that the success of stem cell therapy for damaged tissue will rely on the way the body responds to injury.

Russell, who also serves as the chief innovation officer and executive vice president for the Allegheny Health Network and was the founding director of the McGowan Institute for Regenerative Medicine at the University of Pittsburgh, said when tissue heals, whether in the heart, lungs, liver or other organ, an inflammatory response is initiated and steps are taken to repair the damage by developing scar tissue. However, in utero, fetal cells are capable of regenerating native tissue.

“If I had my appendix out in utero, I would not have a scar,” Russell said. “We do have this ability programmed into our cells, but we begin to lose that ability at around the end of the second trimester. … We get tissue repair, not restoration.”

Russell said the challenge to healing tissue with stem cells is in finding ways to migrate regenerative cells to the damaged tissue instead of inflammatory cells.

“Then the questions become: How do we do that, and what cells do we use; and what can we actually accomplish if we can do that?” Russell said. “If we can send to a site of damage in a body a regenerative cell that will change the orchestration, a new conductor — you can think of inflammatory cells as conductors of the healing orchestra — we’re going to get what is still a natural response, but with a different sounding solution.”

Salamanders are able to regenerate limbs using the same process that fetal cells use, he said.

“Regenerative medicine is a natural process. All we need to do is understand the steps.”

Tissue replacement, such as stem cell-derived tracheal replacements have a mixed history of success, and Russell said much is still unknown about how to grow and replace tissue to function over the long term, but the science has been developing significantly.

“One class of cells has a particularly great potential to effect inflammatory processes specifically,” he said.

Mesenchymal cells — a class of stem cells defined in the 1990s found in dermis tissue, bone marrow, adipose tissue and in varying degrees in other organs — can generate bone, muscle, marrow, tendon and other cells. Russell said although, in rare cases, recipients do reject these cells, they are immunomodulatory, and the tissue from which they are removed may affect their expression later.

Russell said the potential of these cells is high not only because of what they can grow, but because they alter the healing process.

“These cells are truly miraculous,” he said. “They have some unique properties that perhaps no other cells in the body have. They release a whole host of factors that change the nature of the inflammatory response.

“They are really the regenerative cells,” he told the audience, and added that mesenchymal cells are most productive when harvested from younger individuals as well as from female donors.

More than 360 clinical trials are underway and hundreds of thousands of patients have undergone treatment with some kind of cell therapy, but Russell said one study underway is designed to show what the cells do when placed in a patient with CVD.

“The idea is to take a heart that is being supported by an artificial heart in a human and inject stem cells at the time they get that artificial heart,” he said. “Then, when they get a heart transplant later, compare and contrast what those stem cells did while the patient was being supported by the artificial heart.”

Stem cell therapy has shown some moderate success in MI, peripheral arterial disease, stroke and other diseases such as Parkinson’s disease and wound healing, but the factors driving the improvements are unclear, according to Russell. He said it is almost always proven to be safe, and almost always shows at least some functional improvement, but the result does not always include detectable tissue growth.

“Most of the effects of these cells are trophic. It’s not the cells themselves — it’s what they are releasing,” he said.

Russell said research shows that mesenchymal cells have the most impact on diseases related to inflammation, such as Crohn’s disease and arthritis, or show improved healing after surgery.

Immunoengineering islet platelets for patients with type 1 diabetes also “offers hope,” and Japanese researchers were able to reverse macular degeneration using mesenchymal cells, according to Russell.

He cautions, however, that new forms of rehabilitation will need to be developed to support patients, and that potential outcomes are still speculative.

“We like to sell a lot of hope, but there is a ton of hype as well, and a lot of promises. It’s important to remember to under-promise and over-deliver.” – by Shirley Pulawski