- A passage is each time the cell culture is transferred to a new vessel with fresh medium (subculture); Passage 3–4 means the cells have been subcultured three or four times.
- Every round of division ages cells a little; grown for too long, they slow down and change.
- Keeping expansion short and well tested helps keep a cell product young, safe and consistent.
Most people choosing a stem cell treatment ask where the cells come from. Very few ask how they were grown. That second question is less glamorous, and it matters just as much.
Here is the idea behind the phrase you may have seen around: fewer passages, less replication. No microscope needed.
What is a passage?
Cells for treatment start as a small number taken from donated tissue (at Stem Cells Colombia, the Wharton’s jelly of an umbilical cord). To have enough, they are grown in the lab. When a dish gets crowded, the cells are lifted off and transferred to a new vessel with fresh medium. Each of those transfers, called a subculture, is one passage: Passage 3–4 means the cells have been subcultured three or four times.
Every passage means more cell divisions, and more time spent living in plastic instead of in a body. That is where the story gets interesting.
Why do cells get tired in the lab?
Cells can only divide so many times before they slow down. Think of a photocopy of a photocopy: the first few look almost perfect, but with every copy a little more detail is lost.
A well-known study followed mesenchymal cells through their whole life in culture. Over several weeks and passages they grew larger, changed shape, lost some of their surface markers and finally stopped dividing. Crucially, the changes in their genes didn’t appear suddenly at the end. They built up steadily from the very first passage.
Does that change what the cells can do?
It can. Mesenchymal cells help mainly by releasing signals that calm inflammation and support repair. As they age in culture, the mix of what they release shifts, and their ability to become other cell types changes too. A cell that has lost its spark is not the helper you are paying for.
That is why the goal is to have enough cells while asking them to divide as little as reasonably possible.
What about genetic changes?
Every time a cell copies its DNA there is a small chance of a mistake. Researchers who checked clinical-grade mesenchymal cells from several labs did find occasional chromosome changes in culture. The reassuring part: those cells still slowed down and stopped growing on their own, with no sign of turning into something dangerous.
The lesson is to test. Serious manufacturing checks the cells before release instead of assuming they are fine.
Why does consistency matter?
Mesenchymal cells have been tested in clinical trials for decades, and experts point to how the cells are made and handled as a key part of good results. Two batches grown differently can behave like two different products.
So when you compare options, don’t just ask how many cells. Ask how they were grown, how they were tested and how they were stored.
- Where do the cells come from, and how is the donor screened?
- How long are they grown, and how many times are they split?
- What tests are done before release: sterility, identity, viability?
- Who applies them, and where?
Stem Cells Colombia’s answer to the first question: every cord starts with a Colombian donor chosen through an exhaustive selection process. She and her family are screened to confirm that she is free of viruses, bacteria, infections and disease, and more tests are done after the cord is collected. Every batch the clinic receives comes with a quality certificate and a checklist and release document that lists which tests were done and their results.
- When you compare stem cell treatments, ask how the cells were grown, not only where they come from.
- Ask what quality tests the cells pass before they reach you.
- Be wary of any offer that competes only on cell count.
The effect of long culture on mesenchymal cells comes from laboratory studies, mostly on cells from adult tissues: they show steady aging with each passage and occasional chromosome changes, without signs of malignant transformation. Reviews of clinical trials point to careful manufacturing as one key to consistent results.
- Replicative senescence of mesenchymal stem cells: a continuous and organized process · PLoS One, 2008
- Clinical-grade production of human mesenchymal stromal cells: occurrence of aneuploidy without transformation · Blood, 2010
- Mesenchymal Stromal Cells: Clinical Challenges and Therapeutic Opportunities · Cell Stem Cell, 2018
Questions
What does passage number mean?
It is how many times the cell culture has been transferred to a new vessel with fresh medium (subcultured): Passage 3–4 means the cells have been subcultured three or four times. A higher number means more time in the lab.
Are low-passage cells always better?
Lab studies show cells change with every round of division, so shorter expansion helps keep them young. Quality also depends on the source, the testing and how the cells are stored and handled.
Can cells grown in the lab become cancerous?
In studies of clinical-grade mesenchymal cells, occasional chromosome changes appeared in culture, but the cells slowed down and stopped growing without signs of transformation. Testing before release is what matters.
Where do your cells come from?
From the Wharton’s jelly of donated umbilical cords. Stem Cells Colombia doesn’t use cells from bone marrow or fat.