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Johns Hopkins scientists begin first-of-its-kind research to create blood platelets from stem cells

Johns Hopkins scientists have launched a pioneering research program to create, for the first time, human platelet cells from stem cells in order to study inherited blood clotting abnormalities ranging from clots that cause heart attacks and stroke to bleeding disorders. The study is funded by a $9 million grant from the National Institutes of Health (NIH) as part of a nationwide initiative to examine how genetic variations cause heart, lung and blood diseases.

One goal of the Hopkins research is to increase understanding of how genes regulate the function of platelets, which are the sticky cells in blood that are important to stop excessive bleeding. The researchers will also investigate how genetic variations can affect a person's responsiveness to aspirin and other medications that are designed to prevent clotting, in order to find new ways to prevent and treat abnormal clotting. Current anticoagulants, or "blood thinner" medications that are essential to prevent life-threatening complications from some heart or vascular diseases, are not always effective for individuals with certain genetic variations.

The other key aspect of the research will be to develop the technical capacity to produce large numbers of blood platelets from a single individual's blood sample. That way, patients who need platelet transfusions, such as those whose platelets were wiped out following chemotherapy, would be able to be transfused with their own platelets without the risk of rejection that comes with receiving platelets donated from others.

"We will work to develop a completely new approach to generating blood cells for people who are desperately in need of chronic infusions," says Lewis Becker, M.D., professor of medicine and cardiologist at the Johns Hopkins University School of Medicine, who is the co-principal investigator of the study, called Functional Genomics of Platelet Aggregation Using iPS and Derived Megakaryocites.

To begin the research, small blood samples will be taken from 400 adult study volunteers. White blood cells from those donated samples will be transformed into immortal induced pluripotent stems cells, or iPS cells. Those iPS cells can be reprogramed into any type of human tissue. In this case, they will be converted into megakaryocytes, which are few in number, reside in bone marrow and produce platelets.

"We are essentially turning back the clock, transforming these adults cells back to their origins into an embryonic-like state," says Linzhao Cheng, Ph.D., professor of medicine and associate director for basic research in the Division of Hematology. He is also a member of the Johns Hopkins Institute for Cell Engineering and a co-principal investigator of the study.

"The techniques we will use for this study will also be applied to increase understanding of other human diseases. For the first time, we will have a laboratory system to study how human gene variants affect the function of cells," Cheng adds.

The blood samples will come from a large group of people who previously participated in the Johns Hopkins GeneSTAR study, a genetic research initiative with a database of 4,000 people who have family members with early heart disease. That study, which was the largest platelet function study in the world, uncovered an important genetic region related to platelet function and the effect of aspirin on blood clotting.

"From GeneSTAR, we already know that these individuals have inherited genetic variants that affect their platelet function. We will ask some of them to come back to give a small blood sample to help us with this new study," says Diane Becker, Sc.D, M.P.H, professor of medicine and director of the GeneSTAR genetic research program in the Division of General Internal Medicine, who is also an investigator on the study.

The five-year study is one of nine new stem cell projects funded by the NIH to examine how gene variants cause disease. "These studies will illuminate how specific genes behave in different tissues and should clarify the mechanisms by which a gene associated with a disease affects the biology of different tissues," says Susan B. Shurin, M.D., acting director of the NIH's National Heart, Lung and Blood Institute. "Understanding the cellular and tissue biology will allow us to develop and test new therapies and prevention methods. These approaches, using iPS cells on a large scale, could improve the predictive value of preclinical testing, benefit regenerative medicine and reduce the need for animal models of disease," she says.


Contact: Ellen Beth Levitt
Johns Hopkins Medical Institutions

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