Part 9 of the PUR-FORM MUSE Cell Series
Bone marrow, adipose tissue, Wharton’s jelly, placenta, and why the source may matter
In Part 8, we followed an intravenously administered MUSE cell from the IV bag into the circulation and toward injured tissue.
Now we need to go one step backward and ask:
Where did that MUSE cell come from in the first place?
Dr. Mari Dezawa and colleagues originally identified MUSE cells as a naturally occurring population of stress-enduring, pluripotent-like cells found within mesenchymal tissues. In this series, when I refer to MUSE cells, I mean the Dezawa MUSE-cell platform.
Researchers have identified or reported MUSE cells in several adult and perinatal tissues, including bone marrow, adipose tissue, Wharton’s jelly, and placenta.
At first glance, it might seem that the tissue containing the greatest number of MUSE cells should automatically be the best source.
But regenerative medicine is rarely that simple.
The source matters, but so do donor age, cell quality, expansion characteristics, manufacturing consistency, potency, and the condition of the cells by the time they reach the patient.
The better question is not which tissue has the most MUSE cells, but which source produces the best final MUSE-cell product for the clinical goal.
MUSE Cells Are Not Limited to One Tissue
A key feature of MUSE biology is that these cells occur naturally.
They are not genetically reprogrammed in the way induced pluripotent stem cells are.
Instead, MUSE cells exist as a small population within certain mesenchymal tissues and can be identified using characteristic markers, including SSEA-3.
That means a MUSE cell is defined primarily by its biological identity and function, not simply by the tissue it came from.
A MUSE cell from bone marrow and one from Wharton’s jelly may share key defining characteristics, but that does not mean every source is biologically identical.
The surrounding tissue helps shape the cell’s history, and that history may matter.
Bone Marrow: Where Much of the MUSE Story Began
Bone marrow has played a major role in regenerative medicine for decades.
It contains hematopoietic stem cells, stromal cells, immune cells, vascular cells, extracellular matrix, and a large network of signaling molecules.
Researchers identified MUSE cells within bone-marrow-derived mesenchymal populations early in the field’s development.
Much of the foundational work on MUSE-cell stress resistance, homing, differentiation, and repair has involved bone-marrow-derived cells.
But bone marrow also has limitations.
Collection is invasive, the proportion of MUSE cells can be relatively small, and donor age matters.
The marrow of a healthy 25-year-old is not biologically identical to that of a 75-year-old with chronic inflammation, metabolic disease, or age-related changes in the stem-cell environment.
So bone marrow is scientifically important, but it may not always be the most practical source for large-scale allogeneic manufacturing.
Adipose Tissue: Accessible and Abundant
Adipose tissue offers a different advantage: it is usually abundant.
Fat contains stromal and vascular cell populations, and researchers have identified MUSE cells within adipose-derived cell preparations.
From a practical standpoint, adipose tissue is relatively accessible and can yield a large amount of starting material.
But more starting tissue does not necessarily mean a better final product.
Adipose tissue is biologically active.
Obesity, insulin resistance, inflammation, vascular health, and aging can affect its cellular environment.
So once again, the important question is not simply how many cells were collected, but how many have the identity and functional characteristics we actually want to deliver.
That takes us back to an earlier article in this series:
What’s Actually in the Vial?
Wharton’s Jelly: A Young Perinatal Source
Wharton’s jelly is the gelatin-like connective tissue inside the umbilical cord.
Unlike bone marrow and adipose tissue, it is perinatal tissue.
That makes it interesting for several reasons.
The tissue is biologically young.
It has not been exposed to decades of aging, metabolic stress, inflammation, and environmental damage.
It is also collected after birth, so obtaining the tissue does not require an invasive procedure for the donor.
For cell manufacturing, Wharton’s jelly may also provide an attractive starting point for producing larger, more standardized cell batches.
Potential advantages include younger starting biology, noninvasive collection, scalability, donor screening, and manufacturing consistency.
Perinatal does not automatically mean better.
A young tissue source may offer important advantages, but the final product still has to be tested.
The cells still need the right identity, still need to function properly, and the manufacturing process still has to preserve the biology we are trying to deliver.
A young donor source can be an advantage. It is not, by itself, proof of a superior therapy.
Placenta: Another Perinatal Source
The placenta is another intriguing source of regenerative cells.
It is a large, highly vascular organ that develops specifically to support pregnancy and is typically discarded after birth.
From a manufacturing standpoint, this makes it attractive.
Placental tissue may provide young starting material, a large number of cells, potential scalability, and a biologically interesting immune environment.
But the placenta is also complex.
- Different regions contain different cell populations.
- Maternal and fetal components differ.
- Isolation methods differ.
- Culture methods differ.
- Expansion methods differ.
Simply calling a product “placenta-derived” tells us surprisingly little.
Two products that both begin with placental tissue may ultimately be very different biologically.
Once again, the tissue source is only the beginning.
Adult vs. Perinatal: Is One Better?
Patients often ask whether younger perinatal cells are automatically better than adult cells.
The answer is:
Not necessarily.
Perinatal tissues may offer several theoretical and practical advantages.
They may have fewer age-related changes, expand more efficiently, and provide more standardized starting material for allogeneic manufacturing.
But cell age is only one variable.
A young cell that is poorly isolated, over-expanded, improperly stored, or inadequately characterized may still be a poor cell product.
Likewise, an adult-derived cell population may retain meaningful biological activity.
Young biology can be an advantage. Manufacturing quality determines whether that advantage is preserved.
Expansion: More Cells, But at What Cost?
For clinical use, cells often have to be expanded.
That means allowing them to divide in culture until enough cells are available for treatment.
Expansion is necessary for scalability, but it also creates a challenge.
Living cells can change as they divide.
With excessive expansion, some cell populations may change in gene expression, metabolism, surface markers, secretory behavior, stress resistance, and, eventually, functional potency.
So manufacturing becomes a balancing act.
We want enough expansion to create a practical cell product, but we do not want to expand the cells so aggressively that we change the very biology that made them interesting in the first place.
From Tissue to Final MUSE-Cell Product
This is why I think it is useful to stop thinking only about the tissue source and instead think about the entire manufacturing pathway.
The process moves from:
Tissue source → isolation and enrichment → cell expansion → identity testing → functional or potency testing → cryopreservation and storage → finished Dezawa MUSE-cell product
Every step can influence the final biology.
The tissue matters. But so does everything that happens afterward.
More MUSE Cells at the Beginning Is Helpful, But It Is Not Enough
If one tissue has more MUSE cells than another, that can certainly be helpful.
It may reduce the amount of manipulation or expansion required.
But starting abundance is only part of the equation.
We still need to ask whether the cells retain their MUSE identity, stress resistance, homing biology, secretome profile, genomic stability, and functional potency.
And we need to know whether the manufacturer can produce the same high-quality product consistently from batch to batch.
Those questions may ultimately be more important than the number of MUSE cells present in the original tissue.
Autologous and Allogeneic Sources Are Different Strategies
An autologous product uses the patient’s own cells.
That avoids donor-recipient differences, but the cells also reflect the patient’s age and health.
An allogeneic product uses cells from another donor.
This enables manufacturers to select donors, screen source tissue, create standardized cell banks, and potentially produce more consistent doses from carefully controlled starting material.
This is one reason perinatal tissues are attractive for allogeneic manufacturing.
But again, the terms allogeneic, Wharton’s jelly, or placental do not automatically tell us whether the final product is high quality.
The finished cell has to prove it.
There May Not Be One “Best” Source
Patients naturally want a simple answer:
Which is best: bone marrow, adipose tissue, Wharton’s jelly, or placenta?
At this point, I do not think the science supports a single universal answer.
Different sources have different advantages.
Bone marrow has a long scientific history.
Adipose tissue is accessible and abundant.
Wharton’s jelly offers young perinatal tissue and manufacturing potential.
Placenta offers another large and biologically interesting perinatal source.
The best source may ultimately depend on the disease, route of administration, manufacturing process, desired dose, the biological function we are trying to preserve, and, most importantly, the quality of the finished product.
The Source Is Only the Beginning
This brings us back to a central theme of the entire MUSE series.
A cell therapy should not be defined by one number or one label.
- Not simply 20 million cells.
- Not simply SSEA-3-positive.
- Not simply Wharton’s jelly.
- Not simply placental.
We need to understand where the cells came from, how they were isolated, how they were expanded, how their identity was confirmed, whether they remain biologically functional, how they were stored, and what reaches the patient at the end of that process.
That is what transforms a tissue source into a meaningful regenerative-cell product.
The Better Question
Which source gives us the highest-quality, most reproducible, biologically functional MUSE-cell product for the clinical goal we are trying to achieve?
That is a much more difficult question, but it is also the one that matters.
The tissue we start with is important. The cell we finish with is even more important.
Dr. P
