Stem Cells Shielded In Immune-Modulatory Alginate Hydrogel Shown To Be Able To Reduce Damage Caused By Heart Attacks

Stem Cells shielded via encapsulation in an alginate based hydrogel were found to be effective in reducing damage caused by heart attacks according to a new study by bioengineers and surgeons from Rice University and Baylor College of Medicine (BCM).


A postdoctoral research associate at Rice University, displays a
vial of alginate capsules loaded with mesenchymal stem cells.
(Photo by Jeff Fitlow/Rice University)

The research that showed shielding stem cells with the novel biomaterial improves the stem cells' ability to heal heart injuries caused by heart attacks was published in the Royal Society of Chemistry journal Biomaterials Science. https://pubs.rsc.org/en/content/articlelanding/2020/BM/D0BM00855A#!divAbstract
 
The study utilizing animal models (rodents) was led by Rice's Dr Omid Veiseh and Baylor's Dr Ravi Ghanta, showed it could make capsules of wound-healing mesenchymal stem cells (MSCs) and implant them next to wounded hearts using minimally invasive techniques.
 
The study showed that within four weeks, heart healing was 2.5 times greater in animals treated with shielded stem cells than those treated with nonshielded stem cells.
 
In the United States, someone has a heart attack every 40 seconds. In almost all cases, an artery that supplies blood to the heart becomes blocked and heart muscle tissue dies due to lack of blood. Hearts damaged by heart attacks pump less efficiently, and scar tissue from heart attack wounds can further reduce heart function.
 
Dr Veiseh, an Assistant Professor of Bioengineering and CPRIT Scholar in Cancer Research at Rice told Thailand Medical News, "What we are trying to do is produce enough wound-healing chemicals called reparative factors at these sites so that damaged tissue is repaired and restored, as healthy tissue, and dead tissue scars do not form."
 
Dr Ghanta, aAssociate Professor of Surgery at Baylor, a cardiothoracic surgeon at Harris Health's Ben Taub Hospital and co-lead author of the study, said previous studies have shown that mesenchymal stem cells or MSCs, a type of adult stem cell produced in blood marrow, can promote tissue repair after a heart attack. But in clinical trials of mesenchymal stem cells, cell viability has been a consistent challenge.
 
He added, "Many of the cells die after transplantation. Initially, researchers had hoped that stem cells would become heart cells, but that has not appeared to be the case. Rather, the cells release healing factors that enable repair and reduce the extent of the injury. By utilizing this shielded therapy approach, we aimed to improve this benefit by keeping them alive longer and in greater numbers."
 
Although a few MSC lines have been approved for human use, Dr Veiseh said transplant rejection has contributed to their lack of viability in trials.
 
Dr Veiseh further added, "They are allogenic, me aning that they're not from the same recipient. The immune system perceives them as foreign. And so very rapidly, the immune system starts chewing at them and clearing them out."
 
Dr Veiseh had spent years developing encapsulation technologies that are specifically designed not to activate the body's immune system.
 
He also co-founded Sigilon Therapeutics, a Cambridge, Massachusetts-based biotech company that is developing encapsulated cell therapeutics for chronic diseases. Trials of Sigilon's treatment for hemophilia A are expected to enter the clinic later this year.
 
He commented, "The immune system does not recognize our hydrogels as foreign, and does not initiate a reaction against the hydrogel. So we can load mesenchymal stem cells within these hydrogels, and the mesenchymal stem cells live well in the hydrogels. They also secrete the same reparative factors that they normally do, and because the hydrogels are porous, the wound-healing factors just diffuse out."
 
Dr Veiseh had shown in prior studies that similar capsules can keep insulin-producing islet cells alive and thriving in rodents for more than six months.
 
For this research study, co-lead author Dr Samira Aghlara-Fotovat, a Rice bioengineering graduate student in Dr Veiseh's lab, created 1.5-millimeter capsules that each contained about 30,000 mesenchymal stem cells. Several of these capsules were placed alongside wounded sections of heart muscle in animals that had experienced a heart attack. The study compared rates of heart healing in animals treated with shielded and unshielded stem cells, as well as an untreated control group.
 
Dr Veiseh added, "We can deliver the capsules through a catheter port system, and that is how we imagine they would be administered in a human patient."
 
He said, "You could insert a catheter to the area outside of the heart and inject through the catheter using minimally invasive, image-guided techniques."
 
The capsules in the research were held in place by the pericardium, a membrane that sheaths the heart. Tests at two weeks showed that mesenchymal stem cells were alive and thriving inside the implanted spheres.
 
Each year more than 780,000 Americans have hearts attacks e, and Dr Ghanta is hopeful that encapsulated  mesenchymal stem cells can one day be used to treat some of them.
 
Dr Ghanta said, "With further development, this combination of biomaterials and stem cells could be useful in delivering reparative therapy to heart attack patients.”
 
Dr Veiseh said the pathway to regulatory approval could be streamlined as well.
 
He added, "Clinical grade, allogenic  mesenchymal stem cells are commercially available and are actively being used in patients for a range of applications.”
 
He also credited Dr Aghlara-Fotovat with doing much of the work on the project. He said, "She basically executed the vision and developed the hydrogel formulation, the concept of how to package the  mesenchymal stem cells within the hydrogel, and she did all the in vitro validation work to show that  mesenchymal stem cells remained viable in the capsules."
 
Graduate student Dr Aghlara-Fotovat is also co-mentored by Ghanta and worked in his lab at Baylor alongside research assistant Aarthi Pugazenthi, including assisting in rodent surgeries and experiments.
 
Dr Aghlara-Fotovat added, "What attracted me to the project was the unmet clinical need in heart attack recovery. Utilizing hydrogels to deliver therapeutics was an exciting approach that aimed to overcome many challenges in the field of drug delivery. I also saw a clear path to translation into the clinic, which is the ultimate goal of my Ph.D."
 
Dr Veiseh added, "I think one of the things that attract students to my lab in particular is the opportunity to do translational work. We work closely with physicians like Dr Ghanta to address relevant problems to human health."
 
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