A Protein Could Make Stem Cell Therapy for Heart Attack Damage More Effective
Replenishing a naturally occurring heart protein could improve stem cell therapy after a heart attack
(PHILADELPHIA) -- Researchers may have found a way to reduce ongoing heart damage that occurs long after a severe heart attack by improving the longevity of stem cells injected into the heart. The new study shows that a protein infused into the bloodstream, can improve the healing properties of stem cell therapy in animal models of the disease.
“The research could eventually make stem-cell therapy a more viable option for treating long-term damage from heart attack,” says senior author Xin-Liang Ma, MD, PhD, Professor of Emergency Medicine at the Sidney Kimmel Medical College of Thomas Jefferson University. The research was published in the high impact journal Circulation. “By replenishing the naturally-produced, heart-enriched, cardio-protective protein, CTRP9, we create a more favorable environment for stem cells to survive and protect against heart injury.”
Although stem cell therapy has seen great success early on, human trials have been unable to fully replicate the success of animal studies. Researchers realized the heart attack creates a hostile or toxic environment that is inhospitable to the injected stem cells. The stem cells die before they can provide benefit to the patient.
Earlier studies from Dr. Ma’s lab published in Circulation in 2013 had demonstrated that CTRP9 levels become depleted after a heart attack, which suggest that the loss of this protein could be part of what shortens stem-cells survival. “That earlier work made us wonder whether we might be able to improve conditions for stem cells if we replaced CTRP9 to normal physiological levels,” said Dr. Ma.
To test their idea, Yajing Wang, MD, PhD, a research associate professor working with Dr. Ma in the Department of Emergency Medicine at Jefferson, and Dr. Wen-Jun Yan, a postdoctoral fellow from the Fourth Military Medical University, China and first author of this study, first infused CTRP9 to normal physiological levels. In animals that received CTRP9 and stem cells survived longer, covered a larger area of damage in the heart, helped facilitate repair, and prevented the formation of further scar tissue, or fibrosis.
In order to help bring this research closer to patient applications, the researchers used a readily available source of stem cells: fat tissue. “Rather than using heart stem cells or bone-marrow-derived stem cells, we chose a source of stem cells that’s more easily extracted. Other sources may offer other advantages, but fat tissue offers the least invasive source of stem cells for a patient,” said Dr. Wang.
They also characterized how CTRP9 changes stem cells’ behavior and secretory patterns. “We demonstrate that CTRP9 stimulates stem cells to secrete a number of proteins and molecules that not only protect stem cells from toxic cellular death, but also shield the heart from oxidative damage after heart attack,” said Dr. Ma. The researchers are currently exploring this and other questions to elucidate the process by which stem cells protect a heart after a myocardial infarction and help translate it for human application.
This research was supported by National Institutes of Health grants HL-096686 and HL-123404 and American Diabetes Association grants 1-15-BS-122 and 1-14-BS-228. The funders had no role in the study design, conduct of the experiments, and interpretation of the data.
Article reference: W. Yan., et al, “C1q/Tumor Necrosis Factor–Related Protein-9 Regulates the Fate of Implanted Mesenchymal Stem Cells and Mobilizes Their Protective Effects Against Ischemic Heart Injury via Multiple Novel Signaling Pathways,” Circulation, DOI: 10.1161/CIRCULATIONAHA.117.029557, 2017.
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