Innovative adult stem cell research by scientists at The University of Texas Health Science Center at Houston (UTHealth) could aid efforts to apply the brakes to stem cells that produce the type of fat ringing the waists of millions. Research appeared today online ahead of the print issue of Cell Stem Cell.
The scientists have developed a bold approach for targeting fat-generating stem cells that one day could aid in the delivery of drugs that slow the cells' ability to direct fat expansion. Because these cells are also used in regenerative medicine, this approach may have wide applications. The cells are termed adipose stem cells.
The researchers used small artificial proteins (peptides) in a mouse model to identify a marker on the surface of adipose stem cells. Markers are molecules specifically expressed on individual cell types. The scientists screened about 100 billion peptides before finding one that was specific for mouse and human adipose stem cells.
"This marker, called delta-decorin, is specifically expressed on the surface of adipose stem cells, which are responsible for the production of white adipose tissue," said Mikhail Kolonin, Ph.D., the study's senior author and assistant professor of molecular medicine at the UTHealth Medical School. "This is the first prospective marker to be discovered for this particular type of adult stem cell."
Alexes Daquinag, Ph.D., the study's first author and postdoctoral fellow at the UTHealth Medical School, said, "In obesity, you have an overgrowth of white adipose tissue. It is made of adipocytes (fat cells) and one way to stop obesity is to target the progenitor cells - adipose stem cells."
Kolonin added, "The existing approaches to identify adipose stem cells are based on combinations of semi-specific markers and are unreliable. Now we are able to target these cells with a new peptide probe for the purpose of tracing them in the body or controlled elimination."
The researchers report that delta-decorin, a modification of a previously defined protein, interacts with another clinically important protein called resistin on the surface of adipose stem cells. "The decorin-resistin connection is particularly interesting because both decorin and resistin have been previously implicated in Type-2 diabetes and other inflammation-related disease," Kolonin said.
"The next step will involve preclinical tests to see if we can develop the identified peptide into compounds that target these adipose stem cells," Kolonin said. "By depleting the adipose tissue progenitors, we may be able to provide long-term control of white fat."
Kolonin believes this approach could complement an anti-obesity compound he developed at The University of Texas MD Anderson Cancer Center before joining the UTHealth faculty. The compound called "Adipotide" works by targeting the blood vessels in fat and is licensed to Ablaris Therapeutics, Inc.
"Helping people lose weight might also reduce their risk of cardiovascular diseases, certain types of cancer, Type 2 diabetes and other obesity-related diseases," said Kolonin. Previous studies in Kolonin's laboratory have demonstrated the role of adipose stem cells in cancer progression.
Other collaborators from the UTHealth Medical School include Paul Simmons, Ph.D., C. Harold and Lorine G. Wallace Distinguished University Chair and director of the Centre for Stem Cell Research; Yan Zhang, M.D., Ph.D., research scientist; and Felipe Amaya-Manzanares, research associate.
The study is titled "An Isoform of Decorin is a Resistin Receptor on the Surface of Adipose Progenitor Cells." The work was supported by Komen for the Cure, the American Heart Association and the Cancer Prevention & Research Institute of Texas.
Kolonin's laboratory is in the university's Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases. He is on the faculty of the UTHealth Graduate School of Biomedical Sciences at Houston and is a John S. Dunn Research Scholar.