May Benefit Patients with Transplants, Hemophilia, Down Syndrome
The new decade may herald an era of cell therapy -- treating human diseases by delivering highly specific beneficial cells. In the wake of an NIH decision late last year permitting federally funded researchers to use new lines of human embryonic stem cells, the door has opened more widely to stem cell research.
Anyone who has ever undergone a bone marrow transplant has received a type of cell therapy, but current progress in stem cell research holds the potential of precisely controlling cell development for a broader variety of clinical treatments than ever before.
Two large federal grants recently awarded to The Children's Hospital of Philadelphia will advance the frontiers of research into cellular therapies. Both programs aim to engineer human cells into new generations of cells and tissues for patients suffering from blood diseases, cancer and, likely, a greater range of other disorders.
One grant focuses on developing human embryonic stem cells (hESCs) to improve platelet supplies for hematology and oncology patients, as well as using platelets to deliver customized proteins to injured blood vessels. The other grant concentrates on creating induced pluripotent stem cells (iPSCs), a type of stem cell that researchers would use to better understand a variety of diseases, and eventually channel into producing healthy replacement tissues for sick patients. Both programs exemplify 21st century cellular therapy.
"Having a larger and higher-quality supply of platelets will benefit many patients," said Mortimer Poncz, M.D., chief of Hematology at Children's Hospital, and co-principal investigator of the $16.8 million, seven-year grant entitled, "Embryonic Stem Cell-Derived Platelets as Cellular Therapeutics." The National Heart, Lung and Blood Institute, part of the National Institutes of Health, issued the grant under a new initiative, the NHLBI Progenitor Cell Biology Consortium.
Platelets are naturally occurring blood cells that help control bleeding and assist in wound healing. Patients receiving chemotherapy and bone marrow transplantation depend on transfusions of platelets to restore levels depleted by their treatments. However, the donor supply is limited, and after multiple transfusions, patients may develop antibodies that attack the donated platelets.
Under the platelet grant, awarded jointly to Children's Hospital and the Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium, researchers will pursue a novel approach—generating platelets from human embryonic stem cells (hESCs). Such cells--derived from human embryos fertilized in vitro fertilization clinics and donated for research purposes--are capable of developing into every type of tissue in the body.
In seeking to control the fate of these hESCs, the two research centers in this collaboration are pursuing complementary approaches. The Children's Hospital group, under Poncz, will focus on generating platelets and their precursor cells from hESCs in laboratory studies. The Washington State team, under co-principal investigator Beverly Torok-Storb, Ph.D., will rely on its expertise in stem cell transplants and animal studies to develop reagents to administer to patients that will stimulate the patients' existing precursor cells to develop into platelets.
At Children's Hospital, two project leaders are prominent stem cell researchers recently recruited to the Hospital's Center for Cellular and Molecular Therapeutics, directed by gene therapy pioneer Katherine A. High, M.D. Paul J. Gadue, Ph.D., and Deborah L. French, Ph.D., will lead important components of the overall program. (Another project leader in the platelet grant, Mitchell Weiss, M.D., Ph.D., also leads a second NIH-funded grant for stem cell research, described below.) Children's Hospital has established a new core facility, the Human Embryonic Stem Cell Core, to supply cells for their studies.
In addition to boosting the supply of platelets to carry out their usual biological roles, the researchers also seek to customize them as drug delivery vehicles. In mouse studies, for instance, Poncz's team previously treated the bleeding disorder hemophilia by loading platelets with the clotting factor that is deficient in that disease. "In addition to investigating platelets for treating hemophilia in people, we will investigate their potential role in delivering other bioactive proteins to sites of vascular injury," said Poncz. "For instance, platelets might deliver an enzyme called urokinase to selectively disintegrate blood clots."
Second grant will investigate induced pluripotent stem cells
A separate grant from the NHLBI also supports stem cell research, but focuses on a more recently discovered type of cell. This two-year, $997,000 grant was awarded to hematologist Mitchell Weiss, M.D., Ph.D. The Grand Opportunity (GO) Grant, funded by the American Recovery and Reinvestment Act, is part of an NHLBI program to support novel research designed to quickly advance an area of biomedicine in significant ways.