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A World of Potential: Stem Cell Research at CHLA

Categorised as: General

Since the late ’80s, physicians and nurses at Childrens Hospital Los Angeles (CHLA) have been working diligently to develop new diagnostic and treatment regimens through stem cell research.
Rachel Ng

The Gene, Immune and Stem Cell Therapy (GISCT) program at the CHLA Saban Research Institute focuses on hematopoietic stem cell (HSC) biology; development, function and diseases of the immune system; B lymphocyte function, erythropoiesis and gene therapy for hemoglobinopathies. The program has also analyzed graft-versus-host disease and immunologic reconstitution, xenotransplantation immunobiology, development of methods for gene therapy using HSC, and trans-differentiation of hematopoietic and embryonic stem cells.

Human hematopoietic stem cells

One of the principal stem cell investigators at CHLA is Dr. Gay M.Crooks, attending physician at the Division of Research Immunology/Bone Marrow Transplant.Her research interest lies in the basic biology of human HSC and progenitors.

“For more than 15 years, we’ve been studying different aspects of bone marrow stem cells,” Crooks says. Physicians in the division provide medical management of patients with diseases treatable by hematopoietic stem cell transplantation (HSCT), including all aspects of pre- and post-transplant care.

The HSCT program is one of the largest, most highly regarded pediatric programs in the world. Physicians are refining techniques of HSCT to benefit children who lack a suitable family donor, including the use of unrelated donor bone marrow or umbilical cord blood, treated to remove T cells. The program, established in 1983, currently performs 45 to 55 bone marrow transplants per year, according to CHLA.

HSC can be isolated from bone marrow, umbilical cord blood and peripheral blood. “[These] stem cells are much better understood and they’re the ones that are used essentially in bone marrow transplantation,” Crooks says. “We use them clinically, as well as study them in basic biology. A great deal has been discovered over the years and continues to be.”

According to Crooks, recent research suggests that HSC, also known as adult stem cells, are able to produce more than just blood. This represents a potentially revolutionary breakthrough in medicine. “Over the last three or four years, people have been wondering whether bone marrow stem cells (HSC) might also make other tissues like liver, brain muscle and so on,” she says

The researchers at CHLA consist primarily of physician scientists who work in the lab and also provide clinical care to bone marrow transplant patients. Crooks says the knowledge they gain in the lab helps doctors with treatment plans. For example, physicians can learn how to manipulate the immune system after transplantation to help speed patient recovery.

“We learn a great deal from our patients that we can then bring back into the lab. And our lab work very much influence how we treat the patients,” she adds.

Expanding nurse role

Crooks says there are more than 50 healthcare professionals working in stem cell or related research at CHLA, among them Kathy Wilson, RN, Dominique De Clerck,
BSN, and Renna Killen, RN, BSN.

Killen is a clinical research nurse in charge of data management. “She is absolutely central to the collection of data and running of the clinical protocols for our various trials,” Crooks says. “She’s very much a part of the stem cell clinical that we do.”
“In addition, we have two of our outpatient coordinator nurses who are very involved with the care and the conduct of research patients outside the hospital,” Crooks says.

Wilson is the outpatient coordinator who handles patient studies necessary for bone marrow stem cell transplant. De Clerck, nurse coordinator for the matched, unrelated donor program, identifies stem cell donors for patients undergoing bone marrow transplant.

“The nurses are predominantly involved in the clinical, translational research,” Crooks explains. Most of CHLA’s outpatients participate in clinical trials. Nursing staff coordinate patient research, making sure all tests are completed and analyzed.

Crooks believes nurses are going to be at the hub of stem cell research trials. “There’s nothing to stop nurses from being part of the development of these trials,” she says.

“There’s no reason it has to be MDs or PhDs. The basic biology is going to be mainly the people in the labs, but we won’t know how useful they are until we get these cells into the clinic and then anybody caring for patients with these disorders will be on the frontline.”

Embryonic stem cells

The newer, controversial embryonic stem cell research has received widespread support, as well as criticism. Currently, funding is available for only 78 existing stem cell lines. According to the National Institutes of Health (NIH), however, as of April 18, 2003, there are only 11 human embryonic stem cell lines that federally supported researchers can purchase.

At CHLA, researchers have been using only two of the cell lines approved by federal regulations. Crooks says that the government restrictions came at an early stage of the research, limiting the expansiveness of the studies.

Recently, a Johns Hopkins University medical ethics panel raised questions about the existing lines approved by the Bush administration. The sanctioned cell lines were initially grown on mouse cells and could potentially leave human immune systems vulnerable to animal viruses. The panel stated that safer stem cells are currently available, but are not eligible for federal funding.

Future of stem cell research

According to the NIH, more analysis is needed for both embryonic stem cell and HSC research. A 2001 study by the agency verifies the impossibility of predicting which stem cells will best meet the needs of basic research and clinical applications.

Crooks agrees with the NIH, saying that both embryonic stem cell lines and HSC research are just beginning. “It’s very much up in the air at the moment as to how either
embryonic stem cell lines or bone marrow adults stem cells are going to be useful therapeutically,” she observes.

For the immediate future, Crooks predicts that scientists will focus on the essential biology of the two types of stem cells and their application in tissue renewal, tissue engineering or tissue transplantation.

“Stem cells are being studied for their potential to make other tissue. In the future, they will impact lots of other disease processes, like liver disease, CNS (central nervous system) disease, muscle disease and certainly cardiac disease,” Crooks says.

The Debate Heats Up

In November 1998, scientists successfully isolated and cultured human embryonic stem cells-sparking a flurry of debate. These cells have the potential to generate muscle cells, nerve cells, heart cells and blood cells. Approximately 128 million Americans suffering from disabling diseases could experience dramatic benefit from continued research.

Conservative groups maintain that embryonic stem cell research is unacceptable since it leads to the death of donor embryos. On Aug. 9, 2001, President Bush limited funding for the research, in spite of its life-saving potential.

“Research on embryonic stem cells raises profound ethical questions, because extracting the stem cell destroys the embryo, and thus destroys its potential for life,” Bush said in a televised speech.

On April 28, 2004, in a bipartisan effort, more than 200 members of the House of Representatives petitioned President Bush to reconsider the restrictions on stem cell research. “Stem cell research is vital and has great potential to help victims of debilitating diseases like cancer, heart disease, diabetes, Parkinson’s, Alzheimer’s, multiple sclerosis and many others,” Rep. Lois Capps says. “Federal funding is essential to the success of this type of research, but, sadly, the current policy that restricts stem cell research is having an extremely adverse effect.”

Great Britain and other European nations are moving forward with fewer restrictions and more funding for embryonic stem cell research. In December 2002, the Australian parliament passed a bill allowing scientists to harvest stem cells from human embryos for research purposes. However, scientists are not permitted to create new embryos or foster any work related to human cloning.

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