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The sturdier sex? — Study by Pittsburgh scientists finds female stem cells work better
April 10, 2007Female stem cells derived from muscle have a greater ability to regenerate skeletal muscle tissue than male cells, according to a study at Children's Hospital of Pittsburgh of UPMC.
The study, which is being published in the April 9 issue of the Journal of Cell Biology, is the first ever to report a difference in regenerative capabilities of muscle stem cells based on sex.
This finding could have a major impact on the successful development of stem cells as viable therapies for a variety of diseases and conditions, according to the study's senior author, Johnny Huard, PhD, director of the Stem Cell Research Center at Children's and the Henry J. Mankin Professor and Vice Chair for Research in the Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine.
"Regardless of the sex of the host, the implantation of female stem cells led to significantly better skeletal muscle regeneration," said Dr. Huard, also the deputy director of the McGowan Institute of Regenerative Medicine. "Based on these results, future studies investigating regenerative medicine should consider the sex of the stem cells to be an important factor. Furthermore, investigations such as ours could lead to a better understanding of sex-related differences in aging and disease and could explain, at least partially, the high variability and conflicting results reported in the literature on stem cell biology."
Dr. Huard's team, and the study's first author, Bridget Deasy, PhD, director of the Live Cell Imaging Lab at Children's Stem Cell Research Center, made the discovery while working with a population of stem cells they isolated in the lab while searching for a cure for Duchene muscular dystrophy (DMD). DMD is a genetic disease estimated to affect one in every 3,500 boys. Patients with DMD lack dystrophin, a protein that gives muscle cells structure. Using an animal model of the disease, his laboratory is using stem cells to deliver dystrophin to muscles.
In this study, Dr. Huard's team injected female and male muscle-derived stem cells into dystrophic mice and then measured the cells' ability to regenerate dystrophin-expressing muscle fibers.
They then calculated the regeneration index (RI) - the ratio of dystrophin-positive fibers per 100,000 donor cells. Only one of the 10 male populations of implanted stem cells had an RI over 200. In contrast, 40 percent of the female stem cell populations had an RI higher than 200, and 60 percent of the female populations of stem cells had an RI higher than the mean RI of the male cells (95).
This difference may arise from innate sex-related differences in the cells' stress responses, according to Dr. Deasy, an assistant professor in the Departments of Orthopaedic Surgery and Bioengineering at the University of Pittsburgh School of Medicine and School of Engineering, respectively.
The investigators examined several aspects of stem cell behavior. They screened for differences in thousands of genes, and they also looked for differences related to estrogen. In many ways the male and female stem cells were similar, Dr. Deasy said.
"The major difference was what we observed after exposing the cells to stress or after cell transplantation in the animals that have muscular dystrophy. Transplantation of female cells leads to a much more significant level of skeletal muscle regeneration," she said. "The male cells exhibited increased differentiation after exposure to oxidative stress, which may lead to cell depletion and a proliferative advantage for female cells after cell transplantation."
Children's Hospital of Pittsburgh
"Regardless of the sex of the host, the implantation of female stem cells led to significantly better skeletal muscle regeneration," said Dr. Huard, also the deputy director of the McGowan Institute of Regenerative Medicine. "Based on these results, future studies investigating regenerative medicine should consider the sex of the stem cells to be an important factor. Furthermore, investigations such as ours could lead to a better understanding of sex-related differences in aging and disease and could explain, at least partially, the high variability and conflicting results reported in the literature on stem cell biology."
Dr. Huard's team, and the study's first author, Bridget Deasy, PhD, director of the Live Cell Imaging Lab at Children's Stem Cell Research Center, made the discovery while working with a population of stem cells they isolated in the lab while searching for a cure for Duchene muscular dystrophy (DMD). DMD is a genetic disease estimated to affect one in every 3,500 boys. Patients with DMD lack dystrophin, a protein that gives muscle cells structure. Using an animal model of the disease, his laboratory is using stem cells to deliver dystrophin to muscles.
In this study, Dr. Huard's team injected female and male muscle-derived stem cells into dystrophic mice and then measured the cells' ability to regenerate dystrophin-expressing muscle fibers.
They then calculated the regeneration index (RI) - the ratio of dystrophin-positive fibers per 100,000 donor cells. Only one of the 10 male populations of implanted stem cells had an RI over 200. In contrast, 40 percent of the female stem cell populations had an RI higher than 200, and 60 percent of the female populations of stem cells had an RI higher than the mean RI of the male cells (95).
This difference may arise from innate sex-related differences in the cells' stress responses, according to Dr. Deasy, an assistant professor in the Departments of Orthopaedic Surgery and Bioengineering at the University of Pittsburgh School of Medicine and School of Engineering, respectively.
The investigators examined several aspects of stem cell behavior. They screened for differences in thousands of genes, and they also looked for differences related to estrogen. In many ways the male and female stem cells were similar, Dr. Deasy said.
"The major difference was what we observed after exposing the cells to stress or after cell transplantation in the animals that have muscular dystrophy. Transplantation of female cells leads to a much more significant level of skeletal muscle regeneration," she said. "The male cells exhibited increased differentiation after exposure to oxidative stress, which may lead to cell depletion and a proliferative advantage for female cells after cell transplantation."
Children's Hospital of Pittsburgh
Stem Cells Current Events and Stem Cells News RSSNew discovery about the formation of new brain cells
The generation of new nerve cells in the brain is regulated by a peptide known as C3a, which directly affects the stem cells' maturation into nerve cells and is also important for the migration of new nerve cells through the brain tissue, reveals new research from the Sahlgrenska Academy published in the journal Stem Cells.
Umbilical cord blood stem cell transplant may help lung, heart disorders
Two separate studies published in the current issue of Cell Transplantation (18:8), - now freely available on-line have shown that transplanted human-derived umbilical cord blood (UCB) stem cells transplanted in an animal model had positive therapeutic effects on specific lung and heart disorders the animal models.
Gene mismatch influences success of bone marrow transplants
A commonly inherited gene deletion can increase the likelihood of immune complications following bone marrow transplantation, an international team of researchers reports in the November 22 advance online issue of Nature Genetics.
New research shows versatility of amniotic fluid stem cells
For the first time, scientists have demonstrated that stem cells found in amniotic fluid meet an important test of potential to become specialized cell types, which suggests they may be useful for treating a wider array of diseases and conditions than scientists originally thought.
First reconstitution of an epidermis from human embryonic stem cells
Stem cell research is making great strides. This is yet again illustrated by a study carried out by the I-STEM* Institute (I-STEM/ Inserm UEVE U861/AFM), published in the Lancet on 21 November 2009. The I-STEM team, directed by Marc Peschanski has just succeeded in recreating a whole epidermis from human embryonic stem cells.
Bone Implant Offers Hope for Skull Deformities
A synthetic bone matrix offers hope for babies born with craniosynostosis, a condition that causes the plates in the skull to fuse too soon.
Your Own Stem Cells Can Treat Heart Disease
The largest national stem cell study for heart disease showed the first evidence that transplanting a potent form of adult stem cells into the heart muscle of subjects with severe angina results in less pain and an improved ability to walk. The transplant subjects also experienced fewer deaths than those who didn't receive stem cells.
Is hepatic differentiation of embryonic stem cells induced by valproic acid and cytokines?
Embryonic stem (ES) cells, known for their capacity to proliferate indefinitely and differentiate into almost all types of cells including hepatocytes, have raised the hope of cellular replacement therapy for liver failure.
Paradoxical protein might prevent cancer
One difficulty with fighting cancer cells is that they are similar in many respects to the body's stem cells. By focusing on the differences, researchers at Karolinska Institutet have found a new way of tackling colon cancer. The study is presented in the prestigious journal Cell.
U of M researchers find 2 units of umbilical cord blood reduce risk of leukemia recurrence
A new study from the Masonic Cancer Center, University of Minnesota shows that patients who have acute leukemia and are transplanted with two units of umbilical cord blood (UCB) have significantly reduced risk of the disease returning.
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