By BETSY TAYLOR
Adult stem cell research, clinical trials and therapies are proliferating in the United States as scientists seek answers to fundamental questions including how to make adult stem cell therapies most effective and safe for patients.
Photo credit: Caladrius Biosciences
A technician with the PCT subsidiary of Caladrius Biosciences performs a step related to cellular therapy manufacturing at PCT's Allendale, N.J., facility. Dr. Robin Smith, who co-organized a recent Vatican conference on regenerative medicine, is the immediate past chair of Caladrius Biosciences' board.
Dr. Robin Smith, the president of a nonsectarian nonprofit focused on accelerating the development of cell therapies called the Stem for Life Foundation, said there are more than 5,300 adult stem cell studies worldwide listed on the National Institutes of Health's clinicaltrials.gov website exploring questions central to the development of cell therapies.
She said researchers investigating therapies using adult stem cells are studying how many cells are needed for effective treatment and the tissue type they're needed from; where they should be delivered to treat a specific disease or pathology; and when during a disease cycle the therapy should be given to achieve the intended result.
The Stem for Life Foundation co-created an international conference on regenerative medicine. Held at the Vatican, it recently convened for the third time, to support the advancement of adult stem cell therapies and other non-embryonic cellular therapies. (See sidebar, below.)
Stem cells have unique regenerative abilities, and in many tissues, they have the ability to function as a repair system for the body. They are distinguished from other cell types by the fact that they are unspecialized cells capable of renewal through cell division and, under certain conditions, they can be induced to become tissue or organ-specific cells, according to the NIH.
Research related to stem cell therapies is being done on three different groups of cells. The first are adult stem cells, which are undifferentiated cells found among differentiated cells in a tissue or organ. According to the NIH, adult stem cells can renew themselves and can differentiate to yield "some or all of the major specialized cell types of the tissue or organ." The second type of cells being studied are cells induced to become stem cells — called induced pluripotent stem cells; and the third are embryonic stem cells.
The Catholic Church opposes embryonic stem cell research because the cells used originate from human embryos and the church's teaching is that any research that involves the direct, intentional destruction of human life should be prohibited, said Fr. Kevin FitzGerald, SJ, the Dr. David Lauler Chair for Catholic Health Care Ethics in Georgetown University's Center for Clinical Bioethics. He is an associate professor in the oncology department of the Georgetown University Medical Center.
Loyola University Health System's Cardinal Bernardin Cancer Center in Maywood, Ill., is among several Catholic universities and research institutions, some with ties to Catholic health care systems, involved with adult stem cell research and clinical trials on new therapies. Loyola University Health System is part of Livonia, Mich.-based Trinity Health.
Treating cancers of the blood
Dr. Patrick Stiff, director of the Cardinal Bernardin Cancer Center, leads research related to several aspects of bone marrow transplants — which rely on adult stem cells — as well as clinical trials on cord blood stem cell therapies. Adult hematopoietic stem cells, which are blood-forming cells from bone marrow, have been used in transplants for more than four decades. Stiff is among those working to improve survival rates of those with blood-related cancers using the latest cellular therapies.
Dr. Patrick Stiff, director of the Cardinal Bernardin Cancer Center, studies cord blood stem cell therapies to improve survival rates of patients with blood-related cancers. His lab is on the Loyola University Medical Center campus in Maywood, Ill.
Patients with leukemia, lymphoma and other blood cancers often receive high-dose chemotherapy and sometimes radiation to kill their cancer cells, but the treatments also kill healthy blood cells. To boost a patient's numbers of healthy blood cells, the patient may receive a transplant of bone marrow stem cells that develop into healthy new blood cells.
Umbilical cord blood stem cells are increasingly used when a patient needs a stem cell transplant but a matched donor to provide the cells cannot be identified.
The umbilical cord blood can be used in these therapies because a perfect match with a donor isn't required to prevent graft rejection and graft versus host disease, a potentially deadly complication. The umbilical cord blood is donated by parents of a newborn and frozen in a cord blood bank until it is needed. In one study led by Stiff, cord blood stem cells — which only consist of about an ounce of blood per donation — were stimulated in a laboratory to increase their numbers, creating about a 14-fold increase in the number of stem cells available for transplant. Cells created through this process were transplanted to 101 leukemia and lymphoma patients.
Those patients were compared to a historical control group of 295 people who had received stem cells from two separate cord blood donors each. It's common for an adult bone marrow transplant recipient to receive stem cells from cord blood from two newborns, because 1 ounce of blood from one umbilical cord is not usually enough for effective treatment in most adults, Stiff explained.
Researchers compared the efficacy of the new treatment with the increased numbers of cells to the established treatment using cord blood from two donors. The 100-day survival of the patients who received the cells stimulated into large numbers in the lab was 84 percent compared to a 100-day survival rate of 75 percent in the historical control group, according to a Loyola University Health System news release from late 2013.
Loyola said patients who received the greater numbers of cord blood cells stimulated in the laboratory were quicker to engraft, or make blood cells on their own, reducing their vulnerability to infections and bleeding.
Work to combat hemophilia
Dr. Carl Freter, interim director of Saint Louis University's Cancer Center and director of hematology and oncology for Saint Louis University's School of Medicine, described how researchers in one of two labs he runs are working with induced pluripotent stem cells derived from hemophiliac patients, where a mutated factor VIII gene is removed and replaced with the correct factor VIII gene. (A mutated factor VIII gene causes hemophilia, a hereditary genetic disorder in which a person's blood does not clot properly.) They are doing lab research in the hopes that these types of genetically engineered cells can one day be transplanted back to patients. They are working to reprogram a patient's own cells to secrete factor VIII, allowing the hemophiliac patient's blood to clot normally. Freter thinks the promising research will continue to move forward into testing on animal models, with the hope that it will advance to clinical trials.Scientific advances
Doctors and researchers closely following adult stem cell research point to a number of areas where progress is being made. G. Ian Gallicano, an associate professor of developmental biology in Georgetown University's Department of Biochemistry, Molecular and Cellular Biology, said he thinks it's possible macular degeneration, a leading cause of vision loss in older adults, will be cured by stem cell therapies. Much of the research into cures for macular degeneration has relied on embryonic and induced pluripotent stem cells, he said. However, he thinks it's possible that, even if research was originally done elsewhere on embryonic cells, in time other types of human cells will be able to be reprogrammed for the same therapeutic effects.
Gallicano, who researches stem cell therapies, uses mouse embryonic stem cells to learn about the cells' properties, and then human adult stem cells or induced pluripotent cells to further his work. He's currently doing research related to diabetes, but didn't want to discuss his current work in detail, as it is the subject of a soon-to-be published paper.
Stem for Life's Smith, too, said adult stem cell therapies are showing promise in many areas, including revascularization, which is the ability to restore blood supply to parts of the body where it has been diminished by cardiovascular diseases, such as stroke or chronic limb ischemia, which is a severe artery obstruction that reduces blood flow to a person's extremities.
Adult stem cell research is going on outside of major academic centers, in settings like the John Paul II Medical Research Institute in Iowa City, Iowa, as well. Dr. Alan Moy, founder of the nonprofit, said the institute collects tissue or blood samples from patients with certain rare diseases to convert cells from the samples into induced pluripotent stems cells, which will include the genetic defect. From there, different drugs can be tested in the search for effective treatments. Moy said his team also is working on developing a universal induced pluripotent stem cell that would not grow abnormally and form tumors, as some stem cells do, and can be tolerated by patients without regard to their unique immune system, much like O-negative blood.
Discoveries change the debate
As scientific advances have been made related to adult stem cell research they've "changed the terrain of the debate," said Fr. FitzGerald. He pointed to the work of an international team led by researchers at the University of Bristol in England on Mogrify, a computational system that predicts how to create any human cell type from any other human cell type. They believe the ability to produce numerous types of human cells using the system will lead to regenerative medicine breakthroughs, possibly bypassing the need to create induced pluripotent stem cells, and the possibility of creating a variety of new tissue therapies.
Julian Gough, bioinformatics professor at the University of Bristol, said in a statement earlier this year when their paper was published in Nature Genetics that Mogrify was used to test two new human cell conversions and succeeded at both the first time. "The ability to produce numerous types of human cells will lead directly to tissue therapies of all kinds, to treat conditions from arthritis to macular degeneration to heart disease. The fuller understanding, at the molecular level of cell production leading on from this, may allow us to grow whole organs from somebody's own cells," he said.
Regenerative medicine conference at Vatican stresses access for all
Both Pope Francis and Vice President Joe Biden called for work in the field of regenerative medicine to include a commitment to making the most effective therapies to fight cancer and other diseases available to all people. Both men spoke in Vatican City on April 29 as part of "The Third International Conference on the Progress of Regenerative Medicine and Its Cultural Impact."
Cardinal Gianfranco Ravasi, left, president of the Pontifical Council for Culture, accompanies Vatican Secretary of State Cardinal Pietro Parolin, center, as he presents Dr. Robin Smith with the insignia denoting her rank as Dame Commander with Star in the Papal Order of St. Gregory the Great. Smith accepts the honor, bestowed by the authority of Pope Francis, during the annual Vatican conference on regenerative medicine in late April. She is president of the Stem for Life Foundation, which co-organizes the conference.
The three-day event from April 28-30 was organized by the Vatican's Pontifical Council for Culture and the Stem for Life Foundation, a nonprofit working to accelerate the development of cell therapies. The conference brought together international leaders, researchers and families affected by illness to raise awareness of scientific advances in regenerative medicine, which is a branch of medicine focused on developing therapies to heal damaged tissue and organs and providing new treatments and cures for disease.
Pope Francis called for work in the field of regenerative medicine to include therapies for patients with rare diseases, to rely on research with unwavering attention to moral issues and to ensure access to care for all people. He said that, taken collectively, rare diseases affect millions of people. "We are called to make known throughout the world the issue of rare diseases, to invest in appropriate education, to increase funds for research, and to promote necessary legislation as well as an economic paradigm shift," the pope said.
Biden, who heads the White House task force on cancer, told conferees that, for the first time in history, oncologists, immunologists, virologists, geneticists, and chemical and biological engineers are working across disciplines on cancer cures. "Coalitions of cancer organizations are aggregating genomics, patients' records, family histories and lifestyles (data) using super computers to find answers that we don't have right now."
Biden said leaders all over the world have asked the United States to collaborate on the fight against cancer. He called for greater global coordination to promote healthy lifestyles that reduce cancer risks and to reduce environmental factors that cause cancers.
Pope Francis greets Vice President Joe Biden at the spring conference on regenerative medicine at the Vatican.
Biden said more work must be done to increase patients' access to the most effective treatments, to share data, to speed medical advances and to make treatments affordable. "The best medicine and treatment can't belong only to the privileged and the powerful. It has to belong to everyone," he said in his remarks.
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