USF neuroscientist advances stem cell therapy for stroke
Dr. Borlongan explores body’s own bone marrow-derived cells as source of repair
– The Lancet Lifeline Interview with Dr. Borlongan
Neuroscientist Cesar Borlongan, PhD, a leading stem cell researcher, has returned to USF where his career began.
Cesar Borlongan has come full circle – back to the University of South Florida College of Medicine, where he began his neurosciences career as a postdoctoral fellow and aspiring stem cell researcher 16 years ago. This fall he joined the USF Center of Excellence for Aging and Brain Repair, where he is a professor and vice chair of research for the Department of Neurosurgery and Brain Repair.
In the interim, Dr. Borlongan was a senior staff fellow at the National Institute of Health’s National Institute on Drug Abuse, where he earned awards for outstanding scientific achievement and research excellence. The distinguished NIH tenure was followed by six years at Medical College of Georgia, where he directed the Institute of Molecular Medicine and the Department of Neurology Cell Transplantation.
“We are fortunate that a neuroscientist of Dr. Borlongan’s caliber has returned to USF,” said Paul R. Sanberg, PhD, DSc, distinguished professor of neurosurgery and director of the Center for Aging and Brain Repair. “He is one of the pioneers in cell therapy research for stroke and has been instrumental in advocating the consistent, rigorous design of preclinical studies so that findings can be readily translated to stroke treatment.”
Throughout his career Dr. Borlongan has focused on advancing stem cell therapy for brain disorders, particularly adult stroke and neonatal stroke. At the Center for Aging and Brain Repair, he works alongside other leading neuroscientists exploring the potential of neural cells and alternatives to embryonic stem cells (including adult bone marrow cells and cord blood cells) as treatments for brain injury and neurological diseases like Parkinson’s, Huntington’s, Alzheimer’s, stroke and ALS.
Dr. Borlongan brought a team of four postdoctoral fellows and a faculty member as well as a five-year NIH grant totaling more than $3.5 million to USF from Medical College of Georgia. He is working with USF Health neurosurgeons and neurologists and researchers at the Byrd Alzheimer’s Center to develop innovative treatments for stroke using stem cells. In particular, he is exploring ways to harness stem cells produced by the body’s own bone marrow – known as endogenous stem cells — to repair or prevent brain damage from stroke.
If even small numbers of these outlying stem cells in the bloodstream could be coaxed to proliferate with growth factors or drugs and honed to the stroke-damaged area of the brain, the potential benefits could be substantial, Dr. Borlongan said. Because the cells originate in the person being treated, they would be recognized as “self” by the body and not trigger a potentially dangerous immune response.
“One of the major obstacles to cell transplantation has been graft rejection. When you introduce stem cells from a donor to a transplant recipient, the graft can always be rejected as a foreign substance. The patient can suffer infection and other adverse side effects,” Dr. Borlongan said. “But these problems, including the need for powerful immunosuppressants following transplantation, could be circumvented by using stem cells that come from the patient.”
Dr. Borlongan (above) brought $3.5-million NIH grant and a team of researchers with him to the USF Center for Aging and Brain Repair, including postdoctoral fellow SeongJin You, PhD (below).
“We’ve learned a lot in the last decade,” said Dr. Borlongan said. “I’m more optimistic than ever that we’ve jumped through the scientific hurdles needed to demonstrate the safety and effectiveness of stem cell therapy in animal models. We know what works in mice – but now we have to apply it to humans!”
Dr. Sanberg and Dr. Borlongan at USF, working with colleagues at the University of Pennsylvania, laid the foundation for the world’s first experimental procedure to repair brain damage in stroke patients. In 1998, surgeons at the University of Pittsburgh implanted human neurons derived from a tumor and rendered benign (hNT-neurons) into the brain of a patient who suffered a stroke the year before. The clinical trial was built in part on USF research showing that the hNT-neurons restored the movement of rats subjected to experimental stroke.
Since then, only a few small clinical trials of cell therapy for stroke have been reported. While there have been no complications directly related to the stem or progenitor cells, evidence about the cells’ effectiveness in restoring function in patients is still lacking.
Many rodent studies have demonstrated that stem cell transplantation — by surgery, direct injections to the brain and less invasive IV infusion, can improve stroke recovery. But, the underlying reasons for the success of these therapies remain largely unknown. The researchers use various strains of rodents and stroke models; they implant, infuse and inject different cell types; they put the cells in different target locations in the brain and employ different behavior tests to assess functional recovery. All these variables, without standardized treatment protocols and outcome measures, make it difficult to compare studies and determine the best conditions for cell therapy following a stroke, Dr. Borlongan said.
Dr. Borlongan is investigating how the body’s own bone marrow-derived stem cells (glowing in center of screen) could be prodded to rescue stroke-damaged regions of the brain.
In an editorial published last year in the journal Regenerative Medicine, Dr. Borlongan called for academia, industry, the NIH and the FDA to adopt translational research guidelines that would promote more consistency in designing preclinical studies and help advance cell therapy for stroke from laboratory to clinic.
“It is imperative for clinical translation that these cells be tested in multiple models of focal stroke, in both genders and in multiple laboratories,” he wrote.
– Story by Anne DeLotto Baier, USF Health Communications
– Photos by Eric Younghans, USF Health Communications
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