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Bentsen Stroke Center awards grants for regenerative medicine research

HOUSTON - (April 30, 2012) - Every year, approximately 795,000 people in the United States suffer a stroke and the late U.S. Senator and Democratic Party vice presidential candidate Lloyd Bentsen was one of them. As the senator and his wife, B. A., dealt with the challenges of stroke, they developed the idea for a stroke research center.

The couple’s efforts led to the 2009 opening of the Senator Lloyd and B.A. Bentsen Center for Stroke Research at The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (IMM), a part of The University of Texas Health Science Center at Houston (UTHealth). Sen. Bentsen died prior to the center’s opening.

In April at the IMM, B.A. Bentsen and one of the couple’s sons, Lan, got updates on six projects funded by the stroke center. The center was launched with a generous gift from the Bentsen family and the center distributes up to $1 million annually for research.

“The primary focus of the Bentsen Stroke Center is to develop cell-based therapeutics, including the use of certain populations of stem cells, to reduce secondary brain injury and enhance recovery,” said Brian R. Davis, Ph.D., interim director of Center for Stem Cell and Regenerative Medicine at the IMM, which is the academic and administrative home of the Bentsen Stroke Center. Davis is the Annie and Bob Graham Distinguished Chair in Stem Cell Biology at UTHealth.

In 2011 and 2012, Bentsen Stroke Center grants were awarded to UTHealth Medical School faculty members Jaroslaw Aronowski, Ph.D.Qi Lin Cao, Ph.D., Charles Cox Jr., M.D., Pramod Dash, Ph.D., Ying Liu, M.D., Ph.D., Sean Savitz, M.D. and Jiaqian Wu, Ph.D. They are the principal investigators for the studies.

Lessen injury progression

When a blood vessel in the brain ruptures, pooling blood accumulates in brain matter and can cause additional if not more serious problems. Aronowski, professor of neurology and director of cerebrovascular (stroke) research, is exploring a natural way to speed up blood cleanup to prevent further brain injury.

This cleanup is normally done by specialized cells called phagocytes. Unfortunately, this process takes weeks, thus allowing blood, which is now outside of the vessel to continue to damage the brain.  Aronowski proposes to speed up the process by modifying the phagocytes. “We identified components of machinery phagocytes used to scavenge and clean up blood debris. Now, we will isolate them from blood, modify their function and reinject them back to see if they do a better cleanup job,” Aronowski said. He plans to conduct a preclinical trial.

Replace damaged nerve cells

When a person suffers a stroke, nerve cells or neurons can begin to die. Regenerative medicine researchers would like to create replacement cells. Cao, associate professor at The Vivian L. Smith Department of Neurosurgery, is conducting a preclinical study to select the best neural cell types to treat stroke.

His goals are to determine the therapeutic efficacy and long-term safety of neural stem cells and to identify the optimal cells for stroke therapy. He plans to use a technique that allows scientists to turn the clock back on adult cells so they can be fashioned into other specialized types of cells. Cao is a member of the Stem Cell and Regenerative Medicine Center and the Mischer Neuroscience Institute at Memorial Hermann-Texas Medical Center.

Baby heart surgery can lead to stroke-like problem

A treatment for babies born with congenital heart disease can sometimes lead to a stroke-like problem. That is because a surgical procedure can reduce blood flow to the brain, which in turn can lead to neurological injury. The incidence of this issue varies from 20 to 50 percent.

Cox is exploring the use of a stem cell therapy to alleviate this side effect of surgery. He is conducting a preclinical test to see if stem cells derived from amniotic fluid can lessen the neurological damage.

If this study proves successful, doctors could one day extract amniotic fluid while the baby is still in the womb, use it to create a supply of stem cells and then administer the cells when the heart problem is being repaired.

“The advantage of this is that by using the patient’s own stem cells, there is no concern of rejection,” said Cox, professor of pediatric surgery, Stem Cell and Regenerative Medicine Center faculty member, director of the Pediatric Trauma Program at the UTHealth Medical School/Children’s Memorial Hermann Hospital and The Children’s Fund Inc. Distinguished Professor in Pediatric Surgery.

Reducing brain damage by controlling inflammation

The inflammation caused by stroke and traumatic brain injury can lead to additional neurological injury. Dash, professor of neurobiology and anatomy and scientific director of Mission Connect, a project of TIRR Foundation, believes that if he can control the inflammation he can reduce secondary injury.

He plans to conduct a preclinical test to evaluate the protective powers of adult stem cell therapy in mitigating post incident inflammation.

Enhance stroke recovery

When you think, your thoughts are transmitted by nerve cells in the brain called neurons. These cells can be destroyed during a stroke and impair the ability to talk, process information and get around. But, the process of regenerating neurons is time consuming and relatively inefficient.

With their grant, Liu and Wu hope to identify the genetic switches needed to more efficiently create these replacement neurons. To do that, they plan to convert adult skin cells into replacement neurons.

While much work remains to be done, the goal of the investigators is to develop replacement cells that could used to reverse the debilitating effects of stroke. Liu and Wu are assistant professors with The Vivian L. Smith Department of Neurosurgery, the Stem Cell and Regenerative Medicine Center and the Mischer Neuroscience Institute.

Learn more about cell therapy

Researchers in Savitz’s laboratory were among the first to explore the use of stem cells to treat stroke. “Animal studies from our laboratory and others have discovered that some types of stem cells improve functional outcome after stroke by reducing stroke damage and repairing white matter injury in the brain,” said Savitz, associate professor of neurology and director of the Vascular Neurology (Stroke) Program at the UTHealth Medical School.

In an effort to determine the impact of the stem cells on stroke injury, he plans to compare magnetic resonance imaging (MRI) images of the brain tissue of stroke patients receiving stem cells to those who did not receive the cell therapy. “These studies will identify important targets of stem cell therapy and allow us to progress to more advanced stages of clinical trials testing the efficacy of stem cells for stroke,” Savitz said.

The Bentsen Stroke Research Center oversight and grant review committee includes the following UTHealth Medical School faculty members: Davis; John H. “Jack” Byrne, Ph.D., chairman of the Department of Neurobiology and Anatomy and June and Virgil Waggoner Chair; James C. Grotta, M.D., chairman of the Department of Neurology, Roy M. and Phyllis Gough Huffington Distinguished Chair of Neurology, co-director of the Mischer Neuroscience Institute and director of the Stoke Program at Memorial Hermann-TMC; John Hancock, Ph.D., chairman of the Department of Integrative Biology and Pharmacology, vice dean for Basic Research, IMM interim director and John S. Dunn Distinguished University Chair in Physiology and Medicine; John B. Holcomb, M.D.,  vice chair of the Department of Surgery, chief of the Division of Acute Care Surgery, Jack H. Mayfield, M.D. Chair in Surgery and director of the Center for Translational Injury Research; and Charles E. Wade, Ph.D., professor of surgery.

Rob Cahill
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