(Circulation. 2001;103:e9032.)
© 2001 American Heart Association, Inc.
Cardiovascular News
Adult Bone Marrow Stem Cells Repair Hearts Damaged by Myocardial Infarction
Research teams from the National Human Genome Research Institute (NHGRI) and the Cardiovascular Research Institute of New York Medical College, in a stunning set of experiments, demonstrated that it is possible to repair heart attack–damaged hearts with an injection of adult mouse bone marrow stem cells. They showed that the injected cells become functioning heart muscle cells and at least partially restore the organ’s ability to pump blood (Nature. 2001;410:701–705).
Their findings, which were reported in the April 5, 2001 issue of the journal Nature, showed that the adult bone marrow stem cells in mice could be induced to become heart muscle cells rather than blood component cells, as might be expected. To identify the transplanted cells, the researchers, led by Donald Orlic, PhD, a staff scientist in the genetics and molecular biology branch of the Division of Intramural Research at the NHGRI, and Piero Anversa, MD, professor of medicine and director of the Cardiovascular Research Institute, marked isolated mouse bone marrow stem cells with a gene that produces a green fluorescent protein. To further insure that the transplanted cells could be differentiated from others, they decided to transplant stem cells from male mice into the hearts of female mice.
They initiated a heart attack in the female mice by typing a suture around a coronary artery. A short time later, they injected the gene-labeled stem cells into the heart muscle adjacent to the damaged tissue. Over the next 7 to 11 days, the stem cells began to multiply and transform into heart muscle cells. They then moved into the damaged area of the heart. On average, after 9 days, the new heart muscle cells occupied 68% of the damaged portion of the heart. During this period, the stem cells also began to produce smooth muscle and endothelial cells, which became new blood cells.
"Initially, I thought if there was a little regeneration, some heart muscle cells forming, then that would be considered successful," said Dr Orlic. "Instead, our expectations were far exceeded in terms of seeing not just heart muscle cells, but blood vessels and functional measurements showing that the repair actually improved cardiac output. It was a wonderful surprise and went far beyond our expectations."
However, the treatment was not uniformly successful, working in only 12 of 30 mice. Scientists think that the difficulty in injecting the stem cells into the tiny, fluttering hearts might be the reason the treatment did not work in all the mice.
In a report in the April issue of the journal Nature Medicine (2001;7:430–436), Silviu Itescu, MD, director of transplantation immunology at Columbia-Presbyterian Medical Center in New York City, and his colleagues identified what they named embryonic angioblasts, cells that are progenitors of the endothelial lining of blood vessels. When these cells were injected into the tails of rats who had heart attacks, they caused angiogenesis or the growth of new blood vessels in the part of the heart damaged by the attack. With an improved blood supply, fewer heart muscle cells died in the area of the attack, reducing damage overall. The treatment also resulted in less scar formation and an overall improvement in pumping function.
Although they are preliminary and not uniform, the findings heartened experts such as Frances Collins, MD, PhD, head of the NHGRI, who said, "This study offers hope that we might one day be able to actually reverse the damage caused by a heart attack. The apparent ability of stem cells in the bone marrow of adult animals to rebuild the heart reveals nature’s remarkably flexible response to disease."
Doctor-Patient E-Mail
Leading the way into a new millennium of physician-patient relationships, 6 Silicone Valley companies that are self-insured have promised to pay physician fees for responding to e-mails from their patients.
The plan, which was launched April 15, 2001, will pay physicians $20 for each e-mail "visit" that involves nonurgent health matters. Calling themselves the Silicon Valley Employers Forum, the 6 companies want to prove that the use of information technology will actually lower costs and improve care.
The companies involved are Cisco Systems, Inc; Oracle Corp; Adobe Systems, Inc; Cadence Design Systems, Inc; and NEC Electronics, as well as a company that wanted its identify kept secret, said AMNews in its April 9, 2001 edition. Approximately 100 doctors were involved in the plan, and they are expected to recruit at least 2000 employees as participants. Giovanni Colella, MD, a psychiatrist who is also chief executive officer of Healinx Corp in Alameda said her company is providing the technology and expects the pilot study to last from 6 to 8 months.
However, the e-mail is not a strict doctor-to-patient contact in this case. It is limited to employees whose health plans are administered by Aetna, Inc and UnitedHealthGroup, Inc. Employees who want to e-mail their doctors access a secure part of the Healinx site and fill out a questionnaire. Before the question gets to the doctor, it is analyzed by the Healinx computer system, which recommends treatment guidelines to the doctor.
Retroviral Footprints May Point to Cause of Some Schizophrenia
Researchers at Johns Hopkins Children’s Centers have found traces of a retrovirus in the cerebrospinal fluid of 30% of people with acute schizophrenia and 7% of those with a chronic form of that mentally disabling disease (Proc Natl Acad Sci U S A. 2001;98:4634–4639).
In their studies, the researchers found molecular sequences homologous to those of the retroviral pol genes in 10 of 35 people with recent-onset schizophrenia or related disorders. They also found the retroviral sequence in the cerebrospinal fluid of 1 of 20 people with chronic disease.
No retroviral sequences were found in the spinal fluid of 22 people with neurological diseases of noninflammatory origin or in 30 people who had neither neurological nor psychiatric disorders. In their report in the Proceedings of the National Academy of Sciences on April 10, 2001, the researchers wrote, "The nucleotide sequences identified in the cerebrospinal fluids of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus."
"While a low level of retrovirus expression occurs in most human tissues, we found an unexpectedly high level of expression in the cerebrospinal fluids from individuals who had a recent onset of schizophrenia," said Robert Yolken, MD, director of the Stanley Division of Developmental Neurovirology and a principal investigator in the research. "A significant portion of the people with schizophrenia in our study population had active expression of the retrovirus, whereas individuals without schizophrenia lacked the footprint."
"Although our report doesn’t explain why the retrovirus becomes active in the first place, it presents clues as to what may happen when it does become active," Dr Yolken said. "Our ultimate hope is that we can interfere with the retrovirus by preventing it from becoming active. If we can do that, it may give doctors another method of treating schizophrenia."
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