Not All Stem Cells Behave Exactly the Same
When we talk about umbilical cord-derived mesenchymal stromal cells, or UC-MSCs, it can be easy to think of them as one uniform type of cell. In reality, cells collected from different umbilical cords can behave differently in the laboratory. Some may grow faster, while others may be better at interacting with the immune system.
That natural variation can create a challenge for regenerative medicine. If researchers want to develop consistent UC-MSC-based treatments, they need a reliable way to make sure the cells used from one batch to another have similar biological properties.
A 2025 study published in Stem Cell Research & Therapy explored an interesting solution: instead of relying on cells from just one donor, what if researchers carefully selected cells from several donors and combined them?
Putting Different Donors to the Test
Researchers collected umbilical cords from 10 healthy donors and isolated UC-MSCs from each one. They then tested how well the cells could regulate immune activity, particularly their ability to slow the growth of T cells, which are important players in the body’s immune response. The results showed just how different UC-MSCs can be from donor to donor.
Based on how strongly the cells suppressed T-cell growth, researchers divided the donors into three groups:
- High immune-regulating ability
- Medium ability
- Lower ability
The team then combined cells from donors with different strengths to see whether pooling them could create a more balanced and consistent cell product.
Combining Cells Helped Even Things Out
The pooled UC-MSCs included cells from high-, medium-, and lower-performing donors. One of the clearest findings was that pooling reduced some of the biological differences between individual donors.
For example, cells from the lower-performing donor grew more slowly than cells from the other donors. When the cells were pooled together, their overall growth became more consistent. Researchers also found encouraging changes in the cells’ immune-regulating activity.
When exposed to an inflammatory environment in the laboratory, pooled UC-MSCs suppressed T-cell growth more strongly than the lower-performing donor cells on their own.
In one test, the pooled cells reduced T-cell expansion by about 88%, compared with roughly 61% for the lower-performing cells. In another condition, pooled cells reached about 91% suppression, significantly higher than the calculated average of the individual donors.
Stronger Cells Helping the Group
Perhaps the most interesting part of the study was what happened when researchers mixed stronger and weaker-performing UC-MSCs together. Even when there were twice as many lower-performing cells as higher-performing cells, the pool still showed improved immune-regulating properties. The researchers believe there may be communication happening between the cells, allowing stronger-performing UC-MSCs to influence the behavior of the others.
The exact reason is not yet fully understood, but the finding raises an interesting possibility: carefully selecting and combining donors might help researchers create a cell product that is more predictable than relying on a single donor alone.
What About Immune Rejection?
Combining cells from several donors naturally raises another question: could putting different donors together make the final product more likely to trigger an immune reaction?
In this laboratory study, researchers did not find evidence that pooling the cells created a cumulative increase in the immune markers they were monitoring. The pooled cells showed immune-related characteristics similar to those of the strongest individual donor, which the researchers described as encouraging for the future development of donor-derived UC-MSC products.
A Step Toward More Predictable Cell Therapies
This study was performed in the laboratory rather than in patients, so it does not tell us whether pooled UC-MSCs will produce better clinical outcomes. What it does address is an important challenge that happens behind the scenes in regenerative medicine: consistency.
The researchers showed that UC-MSCs from different donors can vary considerably, but carefully combining selected donors may help reduce those differences and improve some of the cells’ immune-regulating properties.
That could eventually make it easier to produce larger, more standardized UC-MSC-based therapies for research into immune and inflammatory conditions.
More testing will be needed before this approach can be translated into patient care. Still, the study offers a fascinating reminder that advancing regenerative medicine isn’t only about discovering what cells can do but it’s also about learning how to make those cells reliable, consistent, and ready for future clinical use.
Source
Mebarki M, Moine-Picard C, Enjaume-Rauch R, et al. Pooling umbilical cord-mesenchymal stromal cells derived from selected multiple donors reduces donor-dependent variability and improves their immunomodulatory properties. Stem Cell Research & Therapy. 2025;16:252. doi: 10.1186/s13287-025-04361-y. Available from: https://link.springer.com/article/10.1186/s13287-025-04361-y
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