Study Suggests Smokers Needing Stem Cell Therapy Would Do Better with Donated Cells

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Smoking dramatically decreases the regenerative ability of stem cells, according to a study recently published in the journal STEM CELLS. These findings suggest that a smoker in need of stem cell therapy might fare better if the cells he receives are donated by a nonsmoker — counter to the alternative approach of using the patient’s own stem cells whenever possible to reduce the chance of rejection.

“Multiple clinical trials have suggested that cell-based therapies could be used to effectively treat a variety of conditions,” said Keith March, M.D., Ph.D., director of the University of Florida’s Center for Regenerative Medicine (http://regenerative.medicine.ufl.edu/). He led the study along with UF colleague Dmitry O. Traktuev, Ph.D., and graduate student Daria Barwinska, Ph.D. “Many of these trials involving adipose-derived cells use autologous cells (that is, the patient’s own cells). While the vast majority of preclinical studies are routinely conducted with cells obtained from relatively healthy donors, the patients that require cardiovascular and other therapies are primarily of advanced age with multiple medical issues. In some instances, they also have a history of potentially toxic recurrent exposure such as with smoking,” he added.

This discrepancy between experimental “best case scenario” studies and ailing patient populations needing therapy supported the need for a careful evaluation of the therapeutic properties of progenitor/stem cells obtained from donors well-matched to the clinically targeted patient population, surmised Dr. Barwinska.

“With more than a billion smokers worldwide, according to the World Health Organization, and smoking implicated as a prominent factor in a wide array of illnesses, we felt a look at this would yield important information,” Dr. March said.

The team, which also included scientists from Indiana University and the University of Colorado, tested their hypothesis on mice. They looked at the ability of adipose stem/stromal cells (ASCs) to improve blood flow after an experimentally induced decrease in blood perfusion to one of the animal’s hindlimbs. ASCs are a highly attractive type of adult stem cells for clinical applications, as they are abundant in fat, have a high proliferative potential, and can easily be obtained from adults in a minimally invasive procedure.

One group of mice with compromised blood flow was treated with human ASCs obtained from smokers, whereas the second group was treated with human ASCs taken from nonsmokers. The results revealed that the animals receiving the smokers’ cells showed a dramatically impaired blood flow recovery compared to those receiving the nonsmokers’ cells. The decrease in therapeutic activity of ASCs from smokers was accompanied by their limited potency to support blood vessel growth. The same held true in a second test in which the stem cells originated from mouse fat, rather than human. (In this instance, one group of the donor animals was exposed to smoke while another group was not.)

“The demonstration that smokers’ adipose-derived Stem Cells have impaired ability to heal an ischemic condition is important and is data that might help some smokers think strongly about quitting or decreasing cigarette usage.” said Jan A. Nolta, PhD, Editor-in-Chief of STEM CELLS and director of the Stem Cell Program and Institute for Regenerative Cures at UC Davis School of Medicine, “This type of stem/progenitor cell can be considered a “first responder” for ischemic tissue events, and they work to try to repair the damage. If they are impaired, there could be a reduced chance for the tissue to heal itself.”

“These discoveries have important implications for clinical trials involving autologous ASCs and perhaps mesenchymal stem cells, too,” Dr. March said. “Specifically, they suggest that active smokers or even patients with a recent history of smoking should be excluded from initial clinical trials with autologous cell therapies, or at least be evaluated as a separate population. It also suggests that donated cells may be the preferred therapy for smokers.”

The full article, “Cigarette Smoking Impairs Adipose Stromal Cell Vasculogenic Activity and Abrogates Potency to Ameliorate Ischemia,” can be accessed at http://www.stemcells.com.

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