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Source of stem cells is crucial in ischemia research

February 20, 2014

Stem cells from human umbilical cord blood trigger growth
of muscle and blood vessels in the legs of mice with tissue ischemia
TORONTO — For people at risk of the devastating ulcers and gangrene associated with type 2 diabetes, stem cell therapy could offer some hope for a new, effective therapy, according to research just published from Mount Sinai Hospital.
In the study, damaged muscle and blood vessels in mice with peripheral vascular disease showed “substantial” rapid healing after the injection of human umbilical cord blood stem cells. The research was lead by Associate Scientist Dr. Ian Rogers (photo) of the Lunenfeld-Tanenbaum Research Institute at Mount Sinai. It was published online (January 18, 2014) in Stem Cell Review and Report. 
The human stem cells that were injected in the mice triggered the mice’s own stem cells to grow healthy, muscle and blood-vessel tissue. That accounted for about 90% of the healing that was observed, while the other 10% of healing was due to the injected stem cells growing tissue directly.   
“This is the type of rapid, profound improvement that we seek for people who suffer from peripheral vascular disease.  They need blood vessels that can effectively pump blood through their feet and legs,” Dr. Rogers says. He is also an Assistant Professor of Obstetrics and Gynaecology at University of Toronto.
Peripheral vascular disease is the failure of the small blood vessels to keep blood flowing in the feet and lower legs, leading to skin breakdown and wounds that can be difficult or impossible to heal. In practical terms, treating or preventing peripheral vascular disease means preventing the wounds and gangrene that lead to foot and leg amputation. Diabetes is the leading cause of foot and leg amputation in Canada and the US. 
Stem cells from umbilical cord blood
In Dr. Rogers’ research, the key to success was using human stem cells from umbilical cord blood and nourishing them with human growth factors prior to injection in the ischemic mice. Although parallel research on using stem cells from the adult bone marrow are ongoing and show promise, stem cells from umbilical cord blood have advantages. They are young cells, and as well, harvesting umbilical cord blood is noninvasive because it is collected from umbilical cords during normal births and saved for medical use. “There’s a good chance that using cells from umbilical cord blood will be more efficient and cost-effect as well as therapeutically effective,” Dr. Rogers adds. 
Dr. Rogers’ team used frozen stem cells from the umbilical-cord blood bank at the Research Centre for Women’s and Infants’ Health, Mount Sinai Hospital. The scientists nurtured the stem cells with human growth factors prior to injection in the mice. The team also tested the stem cells for safety, and found no negative results.
“This paper shows that not all stem cells are equal for all purposes,” Dr. Rogers adds.  “The source of human stem cells — and how they are prepared — can make a big difference.”
Given the positive results for mice with PVD, the next step will be further testing to prepare for human trials, Dr. Rogers says.
Dr. Jim Woodgett points both to the scope and depth of stem cell research at the Lunenfeld-Tanenbaum and to the collaborative ethic within Mount Sinai Hospital. “Not only do we have some of the top stem cell science and diabetes research in the world, but we have all the resources and teamwork brought by our partnering clinician scientists. Research of this calibre is only possible because of the nexus of excellence in the Lunenfeld-Tanenbaum and in the hospital, as well as in our research networks,” he says.  Dr. Woodgett is Director of the Lunenfeld-Tanenbaum.

"We report here that culturing CD34+/CD45+ blood cells from frozen umbilical cord blood units in a medium supplemented with FGF4, SCF and FLT3-ligand produced a population of cells that remain CD34+/CD45+ but have an increased capacity for tissue healing."  — From the abstract

The paper is titled “An Expanded Population of CD34+ Cells from Frozen Banked Umbilical Cord Blood Demonstrate Tissue Repair Mechanisms of Mesenchymal Stromal Cells and Circulating Angiogenic Cells in an Ischemic Hind Limb Model.” The research was funded by Canadian Institute for Health Research, Canadian Stem Cell Network, Mount Sinai Hospital Foundation, MaRS Innovations Proof of Principle Grant, Canadian Foundation for Innovation LEF Project, and Insception-Life Banks.



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