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"Stromal" vs. "stem" cells.
Why many researchers now say "mesenchymal stromal cells" instead of "stem cells," and what the change means when you are comparing clinics.
Direct answer
"Mesenchymal stem cells" and "mesenchymal stromal cells" are often used interchangeably. The International Society for Cellular Therapy (ISCT) prefers "stromal," because most of these cells have not been shown to meet the scientific definition of a stem cell. Research since then suggests their main effect in the body comes from signaling and adjusting immune activity, and not from turning into new tissue.
01 · How we got here
The terminology shift.
The name "mesenchymal stem cell" was coined in 1991 for plastic-adherent, spindle-shaped cells from bone marrow that could be coaxed into bone, cartilage, and fat lineages in a culture dish. The word "stem" carried implicit promise: these cells would, presumably, do in vivo what they did in a petri dish: differentiate into new tissue and regenerate damaged organs.
Two decades of clinical and translational work has not borne that out. As best we understand it, the main effect of MSCs in the body comes from what they release (growth factors, cytokines, and extracellular vesicles) and from how they adjust the local immune and repair environment.1,2 Turning into new tissue appears to play little part.
In 2005, the ISCT recommended calling these cells "multipotent mesenchymal stromal cells," and reserving "stem cell" for cells shown to renew themselves and form new tissue in the body, which most bone marrow cell populations have not been shown to do.9
In 2017, Arnold Caplan, the researcher who coined "mesenchymal stem cell" in the first place, published a widely cited piece proposing the term be reframed entirely: not stem cell, but "medicinal signaling cell."4 In 2019, the ISCT reaffirmed its position: "stem" should be used only when there is evidence the cells renew themselves and form tissue.10
What the shift means in plain terms
The word "stem" suggests these cells become new tissue. The word "stromal" suggests they support an existing tissue's repair machinery. The first is mostly a hope. The second is closer to what the research shows so far.
02 · What an MSC is, technically
The ISCT defining criteria.
The ISCT's 2006 position statement set three minimal criteria for a cell to be called a mesenchymal stromal cell:3
- Plastic adherence in standard culture conditions.
- Specific surface-marker expression: positive for CD105, CD73, CD90; negative for hematopoietic markers (CD45, CD34, CD14 or CD11b, CD19 or CD79α, and HLA-DR).
- Trilineage differentiation potential in vitro, the cells can be differentiated into osteoblasts, adipocytes, and chondroblasts under standard differentiation protocols.
Notice what's not in the criteria: any requirement for these cells to actually do what "stem cells" do in popular usage, engraft, persist, and differentiate into target tissue in vivo. The defining criteria are about identity in a dish, not function in a person.
03 · The functional reality
What MSCs actually do.
The strongest evidence from in vivo studies is that MSCs act primarily through three mechanisms:
- Paracrine signaling. MSCs secrete growth factors, cytokines, and extracellular vesicles (including exosomes) that influence the cells around them. The signal is local and chemical, not regenerative.2,5
- Immune modulation. MSCs interact with T cells, NK cells, macrophages, and the innate immune system in ways that can dampen pro-inflammatory signaling and shift the local environment toward resolution.6
- Support of endogenous tissue repair. By changing the conditions around them, MSCs may support small blood vessels, adjust inflammation, and signal the body's own repair cells, which could help your tissue repair itself.
What MSCs do not reliably do in human clinical settings: differentiate into the tissue they're injected into, persist long-term as functional new cells, replace damaged organ-specific cells, or regenerate lost neurons or cartilage.7
The Caplan reframe
Caplan, who coined the term "mesenchymal stem cell," argued in 2017 that these cells act mainly as "medicinal signaling cells" that direct the body's own repair, and proposed renaming them on that basis.4
04 · The patient-evaluation angle
Why this matters when you're evaluating a clinic.
When a clinic says "stem cells," the word is doing two kinds of work. One is technical, describing a population of cells that meets the ISCT criteria. The other is implicit, promising that these cells will do what most patients hear "stem cell" to mean: regrow tissue, reverse disease, replace damaged cells.
The second meaning is the one that drives much of the "stem cell" market, and it is the meaning that the science does not currently support.
Verbatim regulatory framing, Boulder Biologics
"Consistent with FDA guidance, we avoid unsupported claims regarding 'stem cell' replacement or regeneration."
Clinics that promise regrowth, reversal, or cure are relying on the second meaning. Patient harm and FDA enforcement have centered on clinics making those promises.
A clinic that says "mesenchymal stromal cells," or explains in plain words that the cells work mainly by sending signals, is describing them the way much of the current research does.
05 · How we talk about it
How Boulder Biologics uses each term.
In our clinical letters, on this site, and in patient conversation:
- Our science page explains both names and the ISCT definition of mesenchymal stromal cells.
- When we talk with patients, we sometimes say "stem cells" because it is the familiar term. When it helps, we explain the difference between stromal and stem.
- We describe what they do in functional terms: signaling between cells, adjusting immune activity, and supporting your own tissue's repair. We do not describe them as regrowing or replacing tissue.
- Some page titles include "(stem cells)" so people searching that term can find the page.
06 · Common questions
Frequently asked.
So are "mesenchymal stem cells" and "mesenchymal stromal cells" the same cells? +
Mostly, yes. Both names usually refer to the same cell population, defined by the ISCT markers above. The difference is in what each name claims. "Stem" implies the cells renew themselves and become new tissue in the body, which has not been shown for most of them in people. "Stromal" describes them as supporting cells, which fits what the human data show so far.
If they don't regenerate tissue, what's the clinical benefit? +
The open question is whether these effects (adjusting inflammation, signaling the body's own repair cells, supporting small blood vessels) lead to less pain or better function that you can measure. For a few uses, early studies point that way. For others, the evidence is early or missing. At your consultation, we go through what is known for your situation.
What about "exosomes" or "extracellular vesicles"? Are those the active ingredient? +
They're part of the active mechanism, yes. Extracellular vesicles (including exosomes) carry signaling molecules from MSCs to nearby cells, and much of the cells' signaling effect appears to travel this way.8 Whether exosomes given on their own, without the cells, have the same effect is still an open research question.
Why not just call them "medicinal signaling cells" like Caplan suggests? +
Some recent papers do use it. It has not replaced "stromal," mostly because "MSC" is so well established as shorthand in research papers, regulatory documents, and trial registries. "Stromal" keeps the familiar abbreviation and is more accurate than "stem."
References
Sources cited.
- Guimarães-Camboa N, Cattaneo P, Sun Y, et al. Pericytes of multiple organs do not behave as mesenchymal stem cells in vivo. Cell Stem Cell. 2017;20(3):345–359.e5.
- Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45(11):e54.
- Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315–317.
- Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;6(6):1445–1451.
- Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017;35(4):851–858.
- Ankrum JA, Ong JF, Karp JM. Mesenchymal stem cells: immune evasive, not immune privileged. Nat Biotechnol. 2014;32(3):252–60.
- Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824–833.
- Perets N, Betzer O, Shapira R, et al. Golden exosomes selectively target brain pathologies in neurodegenerative and neurodevelopmental disorders. Nano Lett. 2019;19(6):3422–3431.
- Horwitz EM, Le Blanc K, Dominici M, et al. Clarification of the nomenclature for MSC: the International Society for Cellular Therapy position statement. Cytotherapy. 2005;7(5):393–395.
- Viswanathan S, Shi Y, Galipeau J, et al. Mesenchymal stem versus stromal cells: International Society for Cell & Gene Therapy (ISCT) Mesenchymal Stromal Cell committee position statement on nomenclature. Cytotherapy. 2019;21(10):1019–1024.
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