These synthetic stem cells offer therapeutic benefits comparable to those from natural stem cells and could reduce some of the risks associated with stem cell therapies. Additionally, these cells have better preservation stability and the technology can be generalized to other types of stem cells.
Stem cell therapies work by promoting endogenous repair - they help damaged tissue repair itself by secreting “paracrine factors,” including proteins and genetic materials. While stem cell therapies can be effective, they are associated with risks of tumor growth and immune rejection. Also, the cells themselves are very fragile, and require careful storage and a multi-step process of typing and characterization before they can be used.
“The synthetic stem cells take away the side effects that we see with stem cell infusions,” Caranasos said. “It’s a big step forward in stem cell therapy.”
The research appears in the journal Nature Communications and was published online on Jan. 3, 2017.
Cheng led the team in developing the synthetic version of a cardiac stem cell that could be used in off-the-shelf applications. He is associate professor of molecular biomedical sciences at NC State University, associate professor in the joint biomedical engineering program at NC State and UNC, and an adjunct associate professor in the Division of Pharmacoengineering and Molecular Pharmaceutics at the UNC Eshelman School of Pharmacy.
Caranasos is a co-first author on the article. He is a heart surgeon and is assistant professor of surgery in the Division of Cardiothoracic Surgery at UNC. He directs UNC's Adult Cardiac Surgery Program.
The researchers fabricated a cell-mimicking microparticle (CMMP) from poly (lactic-co-glycolic acid) or PLGA, a biodegradable and biocompatible polymer. The researchers then harvested growth factor proteins from cultured human cardiac stem cells and added them to the PLGA. Finally, they coated the particle with cardiac stem cell membrane.
“We took the cargo and the shell of the stem cell and packaged it into a biodegradable particle,” Cheng said.
When tested in vitro, both the CMMP and cardiac stem cell promoted the growth of cardiac muscle cells. They also tested the CMMP in a mouse model with myocardial infarction, and found that its ability to bind to cardiac tissue and promote growth after a heart attack was comparable to that of cardiac stem cells. Due to its structure, CMMP cannot replicate, which reduces the risk of tumor formation.
“The synthetic cells operate much the same way a deactivated vaccine works,” Cheng said. “Their membranes allow them to bypass the immune response, bind to cardiac tissue, release the growth factors and generate repair, but they cannot amplify by themselves. So you get the benefits of stem cell therapy without risks.”
The synthetic stem cells are much more durable than human stem cells, and can tolerate harsh freezing and thawing. They also don’t have to be derived from the patient’s own cells. And the manufacturing process can be used with any type of stem cell.
“We are hoping that this may be a first step toward a truly off-the-shelf stem cell product that would enable people to receive beneficial stem cell therapies when they’re needed, without costly delays,” Cheng said.
The team’s research “will lead to more studies and possible in-human therapies for people with specific heart diseases,” Caranasos said.
“It has been great to collaborate with N.C. State researchers on this cutting-edge technology that will potentially improve care for people in North Carolina and beyond,” Caranasos said.
The work was funded in part by the National Institutes of Health, N.C. State University Chancellor’s Innovation Fund and a University of North Carolina General Assembly Research Opportunities Initiative grant.
Co-first authors of the paper are Caranasos; Deliang Shen of Zhengzhou University in Henan, China; and Junnan Tang of Zhengzhou University in China and the Department of Molecular Biomedical Sciences and Comparative Medicine Institute and the UNC/ N.C. State Department of Biomedical Engineering.
Other collaborators were:
- Zegen Wang of Soochow University, Soochow, China;
- Adam C. Vandergriff, Tyler A. Allen, Michael T. Hensley, Phuong-Uyen Dinh and Jhon Cores of N.C. State’s Department of Molecular Biomedical Sciences and Comparative Medicine Institute and the UNC-N.C. State Department of Biomedical Engineering;
- Tao-Sheng Li of Nagasaki University in Nagasaki, Japan; and
- Jinying Zhang and Quancheng Kan of Zhengzhou University, Henan, China.
- Includes information North Carolina State University News Services with additions from Margaret Alford Cloud, UNC Division of Cardiothoracic Surgery