SYRACUSE, N.Y. — More new therapeutic treatments for various diseases could move into clinical trials and “potentially faster” into mainstream medical use — if scientists could find ways to manufacture “exponentially higher quantities” of the stem-cell components needed for medical testing.

Zhen Ma, an associate professor at Syracuse University, is leading the work to make those cell-manufacturing process discoveries, the university announced Nov. 17. Ma is the Carol and Samuel Nappi research scholar in Syracuse’s College of Engineering and Computer Science. 

The National Science Foundation (NSF) awarded Ma a $500,000 future manufacturing seed grant for the project, which he’s coordinating with bioengineering experts at the Rochester Institute of Technology (RIT).

As Syracuse University describes it, Ma’s project is examining new ways to ramp up the quantity of extracellular vesicles (EVs), produced from mesenchymal stem cells that can be manufactured in a lab to meet the therapeutic “critical need” for biological products. 

The cells have the ability to use EVs to communicate with other cells by transferring proteins, lipids, and nucleic acids using EVs as a compartment. 

EVs produced by mesenchymal stem cells can inhibit inflammation, modulate immune responses, reduce cell die-off, and enhance tissue repair and regeneration, per a university release.

At present, EV manufacturing capacity remains “far below desired needs,” according to Ma. 

“We are currently at the beginning stage, in that engineers can manufacture perhaps 100,000 cells in a lab, although the capacity needed to scale-up production of more than one million cells a day is the level needed to bring EV use to bear in the clinical trial stage,” he added.

With the NSF future manufacturing seed grant, Ma and his research partners are looking to boost EV production in “what would technically be described as integrating human induced pluripotent stem cells for scalability in the donor cell source, genome engineering for scalability in EV biogenesis and advanced nano-membrane technology for scalability in EV purification,” per the release. 

It is a project that can be “potentially transformative” in EV biomanufacturing due to several technological advances that would improve not only the scalability, but also the “consistency and therapeutic potency” of next-generation EVs, Ma said.

Partnering with RIT

As principal investigator on the project, Ma is teaming up with co-principal investigators affiliated with RIT. 

They include Thomas Gaborski, professor and director of the RIT biomedical and chemical engineering Ph.D. program, and Karin Wuertz-Kozak, a professor of biomedical engineering and director of RIT’s tissue regeneration and mechanobiology lab. 

In addition, Aslan (Mehdi) Dehghani, lead extracellular vesicle scientist, is also involved. He is a bioengineer on the corporate research team of Sartorius Stedim North America, one of the largest global biotechnology firms, Syracuse University noted. The company provides products to biopharmaceutical companies and laboratories to simplify and accelerate progress in bioprocessing. 

Dehghani, current collaborator and former trainee of Gaborski, will provides his expertise in EV purification to this project.

In addition to the immediate effort to find ways to boost levels of manufacturing EVs in labs, Ma said the team also has a “longer-term goal.” They want to obtain a “fundamental understanding” of the biogenesis process, regulatory mechanism, physiochemical properties, and biological functions of EVs to “further advance” the biomanufacturing of therapeutic EVs from various stem-cell types. 

That work calls for new expertise in EV biology, bioreactor design, biomanufacturing processing, and quality controls, Syracuse University said.