Speeding Stem Cells From Lab to Clinic

"The workshop was very exciting and stimulating," said speaker Jun Takahashi, MD, PhD, of Kyoto University in Japan, where he works at the renowned Center for iPS Cell Research and Application directed by Shinya Yamanaka, MD, PhD. Yamanaka shared the 2012 Nobel Prize in Physiology or Medicine for his stem cell discoveries.

The event, sponsored by the Cedars-Sinai Board of Governors Regenerative Medicine Institute, drew a sold-out audience of 300 to the campus in June. Besides Takahashi, investigators from the institute, the University of California system, Stanford University, Cincinnati Children's Hospital and Lund University in Sweden presented their latest research projects. Speakers from Origent Data Sciences in Vienna, Virginia, and the U.S. Food and Drug Administration (FDA) added insights from industry and regulators.

Most of the investigators' studies involved induced pluripotent stem cells (iPSCs), which scientists create by genetically altering ordinary adult skin or blood cells so that they can make any tissue cell. These cells can be used to study how diseases develop, to test drug treatments and to generate healthy cells that potentially can replace diseased cells.

"The FDA is committed to advancing the clinical development of cell-based therapies," said Peter Marks, PhD, MD, director of the Center for Biologics Evaluation and Research at the FDA, which has launched programs to expedite evaluation of these therapies. But so far the clinical effect of such treatments have been modest outside of hematologic disorders, which affect blood and blood-forming organs, he explained.

The workshop's presenters are trying to change that picture. Among the diseases they are tackling:

• Amyotrophic lateral sclerosis (ALS): Clive Svendsen, PhD, director of the Board of Governors Regenerative Medicine Institute and professor of Biomedical Sciences, is conducting a clinical trial that combines stem cell and gene therapies. The goal of this line of research is to eventually stall progression of this devastating neurological disorder.
• Parkinson's disease: Takahashi is on a Kyoto University team that implanted progenitor cells of dopaminergic neurons, which make dopamine, into the brain of a Parkinson's patient in October 2018. The goal of this clinical trial is to develop a therapy for this disorder, which involves progressive impairment or death of these neurons. The progenitors were derived from iPSCs. Samuel Sances, PhD, a project scientist at the Board of Governors Regenerative Medicine Institute, is using iPSCs to create dopaminergic neurons on tissue chips to learn how genes may drive Parkinson's.
• Age-related macular degeneration: Dennis Clegg, PhD, from the University of California, Santa Barbara, is using IPSCs to make retinal pigment epithelial cells, which support the eye's photoreceptor cells. Loss of pigment epithelial cell function causes photoreceptor cells to die in this disorder, resulting in loss of vision. The ultimate goal is to replace these cells in patients and "stop macular degeneration in in its tracks," Clegg said.
• Wound-healing disorder: Anthony Oro, MD, PhD, from the Stanford University School of Medicine, is conducting preclinical studies on a rare, gene-based disorder that impairs healing of wounds. His lab is using iPSCs to generate sheets of skin cells that potentially might be grafted onto patients to repair wounds.

The FDA's Marks said a major challenge for the stem cell field is that the public may find it difficult to distinguish science-based clinical trials, such as those discussed at the Cedars-Sinai workshop, from what he called "gray market" regimens offered by various companies to patients.

In an interview, Marks said patients should be wary of a clinical trial offering if they are asked to pay money to participate, if they are not asked to sign an informed consent form or if the trial is not being conducted under an Investigational New Drug Application process involving the FDA.

"The International Society for Stem Cell Research is really important because they are trying to develop stem cell therapies in a scientific and ethical manner," Marks said.