How MSC Products Are Made

Why manufacturing decides what you receive

Two vials can both say "umbilical cord mesenchymal stem cells" and contain meaningfully different medicines. Not because anyone lied on the label, but because MSC is a description of a cell population, not a manufacturing standard, and almost everything that determines potency happens between the donation and the dose.

This article walks that journey: donation, isolation, expansion, testing, freezing, and thawing. It is the practical companion to our comparison of cell sources, and the reason the questions at the end of it are the most useful ones a patient can ask.

Step 1: Donation and screening

Everything starts with tissue. For cord products, that means a donated umbilical cord after a healthy full-term birth, with the donor screened for transmissible disease, a step that costs nothing in patient risk since the tissue is otherwise discarded. For autologous products, the donor is the patient, which makes screening moot and donor health decisive: diabetes and obesity are both associated with degraded MSC function, so the starting material varies with the person.

Step 2: Isolation and the ISCT definition

Cells are separated from the tissue and checked against the standard the field agreed on in 2006, the International Society for Cellular Therapy's minimal criteria: they must stick to plastic, carry a defined set of surface markers, and be able to become bone, cartilage, and fat lineages in a dish.

Those criteria are genuinely useful and deliberately minimal. They establish identity, whether these are MSCs at all, and they say nothing about whether the cells are any good at their job. Identity and potency are different questions, and the gap between them is where product quality lives.

Step 3: Culture expansion

A single donation contains far too few cells for treatment, so they are grown in flasks over weeks until a small sample becomes many doses. This is the step that separates a manufactured product from a same-day preparation, and it changes the cells in ways worth understanding.

Expanded cells are not identical to the cells that were harvested: proteomic profiling of native unpassaged versus culture-expanded MSCs found substantial differences in protein expression. Expansion is not a neutral photocopier; it is a process that shapes the product. It is also what makes testing, banking, and consistent dosing possible, which is why every MSC product used in a registered trial went through it.

Step 4: Passage number, the quiet quality marker

A passage is one round of the growth cycle: cells fill the flask, are lifted off, and are split into fresh flasks. Passage two is a young culture; passage ten has been split many times, and the cells change continuously as that count rises.

Across roughly 7 to 12 passages, human MSCs enlarge, lose the surface markers that define them, lose fat-lineage potential while gaining a bone bias, and eventually stop dividing. In one series, average population doubling fell from 7.7 to 1.2 by the tenth passage, with differentiation capacity dropping from the sixth passage onward. Donor age compounds it: cells from younger donors proliferate further and hold their characteristics to higher passages.

The practical translation: a low-passage and a high-passage product from the same donor are not the same medicine, and passage number is a fair question to ask.

Step 5: Potency testing, the step most often skipped

Here is the uncomfortable centre of MSC manufacturing. When a standardised assay measured immunosuppressive capacity across donors, it varied significantly from one to the next, and the authors noted that release criteria commonly cover identity, purity, and safety while potency is often not assessed at all.

Read that again: products can be released as legitimate MSCs without anyone measuring whether they do the thing they are given to do. The ISCT has since proposed a matrix of immune functional assays as potency release criteria for advanced-phase trials, which is the field trying to close its own gap. Harmonised procedures help but do not erase it; when three laboratories grew cells under one protocol, donor and tissue variability shrank without disappearing.

Step 6: Cryopreservation and post-thaw viability

Doses are frozen for storage and shipping, then thawed at the clinic, and freezing is a violent thing to do to a living cell. Done properly, with controlled cooling and cryoprotectant, cells survive it well; done poorly, a vial can contain a majority of dead cells that still looks like a full dose.

That is why post-thaw viability testing exists: it verifies how many cells are alive and functional in the dose actually administered, not in the batch as it was banked. Research on optimised cryopreservation examines exactly this, preserving functional competence rather than mere survival. A manufacturer who can show you post-thaw numbers is a manufacturer who measured them.

What this means at the clinic

The pros and the cons

Why standards vary so much

Cell products fall between regulatory categories. A drug has a molecular formula; a cell product has a process, and regulators differ sharply on how much of that process they oversee, from full pharmaceutical manufacturing rules to minimal oversight of same-day autologous procedures. Add that potency assays for MSCs are genuinely hard, since the cells work by many signals rather than one, and you get a field where the honest manufacturers test far beyond what is required and the rest do not. The asymmetry is invisible from the outside, which is exactly why asking is worth it.

What the key studies tested

Our framing rule for evidence: a study tests one process, one measurement, one system. Where the evidence sits:

Every study behind this article is filterable in our research library on the Science page.

Questions people ask

This article is for educational purposes only and is not medical advice, a diagnosis, or a treatment recommendation. MSC manufacturing is discussed in the context of the published research; inclusion of a study does not imply a guaranteed outcome. Many of these compounds are investigational and not approved for the uses described in all jurisdictions. Any treatment decision should be made with a qualified physician. Individual results vary.