Wise Young
11-28-2001, 06:19 AM
• Csete M, Walikonis J, Slawny N, Wei Y, Korsnes S, Doyle JC and Wold B (2001). Oxygen-mediated regulation of skeletal muscle satellite cell proliferation and adipogenesis in culture. J Cell Physiol. 189 (2): 189-96. Summary: Major problems in stem cell biology revolve around defining the developmental potential of cell populations and understanding how their potential is maintained or progressively restricted. Oxygen (O(2)) is an obvious environmental factor which has received little attention in culturing skeletal muscle progenitor cells. In this work, we examine the effects of O(2) levels on the developmental potential, proliferative capacity, and phenotype of the adult skeletal muscle fiber progenitor population (satellite cells), and cell lines that model multipotential embryonic paraxial mesoderm from which skeletal muscle develops. Both satellite cell proliferation and survival of mature fibers increased in physiologic (6%) O(2) vs. non-physiologic 20% O(2) used in virtually all traditional cell culture. Six percent O(2) conditions also accelerated the up-regulation of multiple MyoD family myogenic regulatory factors (MRFs). An unexpected finding was that fiber-adherent satellite cells could assume a non-myogenic phenotype. By the criteria of molecular markers and gross lipid accumulation, satellite cells were found to assume an adipocyte phenotype, and did so more prominently in 20% O(2) than in physiologic O(2). Selection of the adipogenic fate and execution of adipogenesis by multipotential mesenchymal cell lines was also dramatically higher in traditional 20 vs. 6% O(2), and decreased adipogenesis in physiologic O(2) was associated with significantly less expression of the adipogenic regulator, PPAR gamma. These results suggest that regulatory pathways affected by O(2) are important for satellite cell proliferation, execution of cell fate, and parent muscle survival in culture, and so may play a role in vivo under normal or pathologic conditions. <http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11598904> Biology Division, California Institute of Technology, Pasadena, California, USA. csete@umich.edu
Wise Young
11-28-2001, 06:21 AM
http://www.stemcellresearchnews.com/new2581.html
Oxygen may be good for you, but itÃ*s not so great for your stem cells, according to a new study by scientists at the University of Michigan Medical School (Ann Arbor, Mich.). Too much oxygen can kill stem cells, slow growth and even trigger an alternate developmental pathway that converts pre-muscle stem cells into fat cells.
The U-M study, published in the November 2001 issue of the Journal of Cellular Physiology, shows that gene expression patterns change significantly when stem cells are exposed to varying amounts of oxygen, and that these changes alter the basic biologic function of stem cells. In addition to its scientific importance, the U-M study could have important clinical implications for treatment of obesity and diabetes.
ìThe more primitive the stem cell, the more sensitive it is to oxygen,î said Marie Csete, M.D., Ph.D., an assistant professor of cell and developmental biology and an associate professor of anesthesiology in the U-M Medical School, who directed the study.
ìWe found that skeletal muscle satellite cells grew faster, lived longer and developed into muscle cells more consistently when cultured with the amount of oxygen found in their natural environment.î In their natural environment in the body, stem cells never are exposed to the amount of oxygen they encounter in the typical biomedical laboratory.
Csete and colleagues compared growth rates and developmental patterns of stem cell lines and skeletal muscle satellite cells grown in a laboratory atmosphere of 20 percent oxygen to cells grown with the 2 percent to 6 percent oxygen levels found inside the body. Csete grows stem cell cultures in a custom-designed facility, which she can adjust to create an atmosphere with specific amounts of oxygen and other gases.
ìThe big surprise was that satellite cells isolated from muscle fibers often converted spontaneously to fat precursor cells, also called adipocytes, when cultured with 20 percent oxygen, especially for long periods of time,î said Csete.
CseteÃ*s study focused on adult stem cells called satellite cells from muscle tissue in adult mice. Unlike embryonic stem cells, which are capable of transforming into any cell in the body, adult stem cells are limited to becoming just a few cell types. The satellite cells in CseteÃ*s study normally develop into muscle cells. They provide a continuous source of new cells to replace those damaged during daily wear-and-tear. Under abnormal conditions, however, Csete discovered they can morph into fat cells instead.
Csete suspects the abnormal behavior of cells grown with lots of oxygen may mimic the reaction of aging cells exposed to free radicals and oxidative stress. ìIt seems plausible that some clinical conditions, such as aging and diabetes, which involve lost muscle mass and increased amounts of fat, may be related to satellite cell adipogenesis or fat cell development,î says Csete.
The toxic effects of oxygen may not be limited to just one type of precursor stem cell. In related experiments, Csete obtained the same results with progenitor cells from the central and peripheral nervous systems of adult mice.
During the five years she has been studying the effects of oxygen and other gases on stem cells, Csete has encountered more than her share of skepticism. ìIt was difficult initially to get people to even consider the idea that oxygen matters, because scientists have been culturing cells the same way for decades.
ìThese studies suggest that the high levels of oxygen used in routine cultivation of stem cells can alter their efficiency,î adds Csete. ìOur results indicate that the conditions under which approved human embryonic stem cell lines were cultured may have limited their potential in important ways.î
In her current research, Csete is focusing on questions related to oxidative stress and muscle-fat conversion in aging. ìOur preliminary results suggest that these stem cells are active players in normal or pathological remodeling of muscle tissue throughout life,î she says. ìThe developmental path they take is very responsive to the oxidative stress around them.î
The U-M study was supported by the Defense Advanced Research Projects Administration (DARPA) of the Department of Defense. U-M collaborators included Nicole Slawny, graduate student; and research associates Yuewang Wei, Ph.D., and Sheryl Korsnes. Other members of the research team from the California Institute of Technology included Jean Walikonis, research scientist; Barbara Wold, Ph.D., professor of biology; and John C. Doyle, Ph.D., professor of control and dynamical systems.
Contact: Journal of Cellular Physiology 189:189-196 (2001). Available at: http://www3.interscience.wiley.com/cgi-bin/issuetoc?ID=85513027
Â*Â*Â*Contact: Dr. Marie Csete, 734-936-4280, http://www.med.umich.edu/cdb/faculty/csete.html