Researchers from the David Geffen School of Medicine at UCLAand the UCLA Henry Samueli School of Engineeringand Applied Science today announced they have transformed adult stemcells taken from human adipose—or fat—tissue into smooth muscle cells, which helpthe normal function of a multitude of organs, including the intestine, bladderand arteries. The study may help lead to the use of fat stem cells for smoothmuscle tissue engineering and repair.
Reported in the July 24 online edition of the Proceedings ofthe National Academy of Sciences, the study is one of the first to show thatstem cells derived from adipose tissue can be changed to acquire the physicaland biochemical characteristics, as well as the functionality, of smooth musclecells.
Smooth muscle cells are found within the human body in the walls of hollow organs like blood vessels, thebladder and the intestines; they contract and expand to help transport blood,urine and waste through the body's systems.
"Fat tissue may prove a reliable source of smooth musclecells that we can use to regenerate and repair damaged organs," said Dr.Larissa V. Rodriguez, principal investigator and assistant professor in thedepartment of urology at the David Geffen School of Medicine at UCLA.
Rodriguez and her team first cultured the adipose-derivedstem cells in a growth factor cocktail that encouraged the cells to transforminto smooth muscle cells. Researchers observed the genetic expression anddevelopment of proteins that are specific to this type of cell. So it lookedlike a smooth muscle cell, but would it act like one?
The next step required testing functionality to see if thecells would contract like smooth muscle tissue. Rodriguez turned to Dr.Benjamin Wu, associate professor of bioengineering at the Henry Samueli School of Engineering and AppliedScience, for help.
Wu's team developed a special device to evaluate the cells'ability to contract by tracking the movement of microbeadsdispersed in a collagen gel embedded with the cells. Researchers addeddifferent pharmacologic agents known to cause contraction or relaxation insmooth muscle.
"We found that the cells did indeed function just likesmooth muscle," Wu said. "The new device allowed us to evaluate drug-inducedchanges in the physical properties of smooth muscle at the celllevel—previously we've needed tissue samples to observe this phenomenon."
To make sure they could reproduce the smooth muscle cellsand to confirm the transformation, Rodriguez and her team cloned one of theprimitive stem cells from the adipose tissue and repeated the experiments on acloned population of cells, with similar results.
"We wanted to make sure it wasn't an isolated case orparticular conditions in the cell cultures that allowed us to create or selectout already existing smooth muscle cells," said Rodriguez, also a member of theUCLA Stem Cell Institute. "We are surprised and pleased with the results andare excited about future applications."
Rodriguez noted the many advantages of using a patient's ownfat stem cells for organ re-growth and tissue regeneration, including the lackof need for anti-rejection medications. For patients with a diseased or absentorgan, who cannot use their own organ tissue for regeneration, adipose stemcells offer an alternative.
Smooth muscle cells have also been produced from stem cellsfound in the brain and bone marrow, but acquiring stem cells from adiposetissue is much easier, and most patients have adipose tissue readily available,according to Rodriguez.
The next step, Rodriguez said, involves identifying anddeveloping the growth factors that will induce transformation of cells morequickly. She is also starting to use smooth muscle cells for tissue engineeringin the urinary tract, including the urethra.
The study was funded by a National Institute of Child Healthand Human Development Building Interdisciplinary Research Careers in Women'sHealth grant, the American Geriatrics Society JahnigenCareer Development Scholars Award, and the National Institute of Diabetes andDigestive and Kidney Diseases.
Other UCLA authors include: ZeniAlfonso and Rong Zhang from the department of urologyat the David Geffen School of Medicine at UCLA; Joanne Leung from the UCLADepartment of Bioengineering; and Louis J. Ignarrofrom the UCLA Department of Molecular and Medical Pharmacology.