The Growing Role of Mesenchymal Stem Cells (MSCs) in Regenerative Medicine

First discovered in the 1970s, mesenchymal stem cells (MSCs) are multipotent stem cells that have since attracted growing interest from researchers who work in various clinical areas, including regenerative medicine.

Because MSCs can immunoregulate and secrete growth factors, they could be of great use in tissue engineering, where donor-to-recipient immune responses and tissue growth are chief concerns.

Combine those benefits with the fact that these progenitor cells have a multipotent mechanism that can turn into a variety of cell types, and it's clear why researchers are excited about their potential. According to Cells, studies involving bones and cartilage, liver, nervous system, heart, eyes, and skin have unearthed new insights into MSC applications in regenerative medicine.

Despite the promise MSCs have shown at the bench, there are challenges hold them back from reaching the bedside — most notably, the most effective and efficient way to scale. A typical MSC therapy requires millions of cells, and harvesting that volume can be difficult.

Still, scaling challenges shouldn't be a barrier to MSC uptake. Scientists have access to myriad tools and technologies that can help them manage and optimize the scale of this exciting treatment pathway.

The Challenges of Working With MSCs at Scale

The big question is obvious: How can scientists possibly make enough MSCs?

"You certainly need a lot of surface area to culture these high volumes of cells, whether that's a static culture like a CellSTACK® culture chambers or HYPERStack® vessles, or using microcarriers in a suspension system," said Hilary Sherman, a senior applications scientist at Corning Life Sciences.

Scientists should consider efficiency and how quickly they can achieve those high numbers, as the quality and treatment value of MSCs diminishes over time, adds Ben Josey, Ph.D., a field application scientist at Corning Life Sciences.

Additionally, you should consider efficiency and how quickly you can achieve those high numbers since the quality and treatment value of MSCs can diminish over extended time in culture, adds Ben Josey, Ph.D.

"You do have the constriction of these being primary cells, rather than cell lines," Josey said. "They have a limited number of times that they can double before they begin becoming senescent and their potential therapeutic efficacy begins to decline."

"These cells come directly from patients, which means there's a lot of variability," Sherman said. "It's not like working with a cancer cell line that has been so modified and controlled that it behaves pretty consistently every time. You could get MSCs from one patient and they behave one way and then see that MSCs from another patient behave slightly differently in growth and doubling."

Standardizing Improvement

MSCs' scale challenges increasingly push scientists toward cutting-edge technologies, such as monitoring controls and bioreactors, to help scale seed chain production more effectively and efficiently. But scale challenges are also spurring a widespread conversation around MSC use standardization.

Until the mid-2000s, there wasn't much guidance to go on.

"There's just a lack of consistency across the board on aspects such as cell densities or culture media," Sherman said. "If you do a literature search for MSCs, you're going to see little mention of those protocols for culturing or even assessing cell quality. And these factors are all important to consider since they can impact the cells themselves as well as the therapies."

In 2006, the International Society for Cell Therapy (ISCT) established guidelines to help researchers manage those conflating factors. In a position paper (and a 2016 update), the ICST issued what it considered the minimum criteria for identifying MSCs. Those guardrails continue to pull the industry toward standardization.

Still, many scientists don't meet the ISCT's minimum criteria when they put together their investigational new drug applications, Josey said. There's room for improvement among researchers interested in MSC studies — and these days, there are more of them than ever.

"We have a massive influx of people from different fields coming into the MSC space, whether they're stem cell scientists, bioprocess scientists, clinicians, you name it," Josey said. "If I had to give one piece of advice, it's that they consider the biology of these specific cells as well as the biology of their therapeutic indication, and then start preparing for their production goals as early and as comprehensively as possible."

Translation: Start with the end goal in mind. Many cell culture equipment providers, including Corning Life Sciences have field applications specialists on staff to help you optimize your scaling process with a platform that supports your research goals. Your research, resources, costs, and labor will benefit from a robust plan and assistance.