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"Stromal" vs. "stem" cells.
A subtle word change with a real meaning. Why most peer-reviewed work now says "mesenchymal stromal cells", and why the change matters for how patients evaluate clinics.
Direct answer
"Mesenchymal stem cells" and "mesenchymal stromal cells" are often used interchangeably, but the science has moved. The International Society for Cellular Therapy and most peer-reviewed work now use "stromal" because it more accurately reflects what these cells actually do: cell-to-cell signaling and immune modulation, not regenerative differentiation into the tissue they're delivered to.
01 · How we got here
The terminology shift.
The label "mesenchymal stem cell" was coined in the early 1990s, when researchers first isolated 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. The dominant effect of MSCs in the body, as best we understand it, is not differentiation into the tissue they're delivered to. It's secretion, growth factors, cytokines, extracellular vesicles, and modulation of the local immune and tissue-repair environment.1,2
In 2006, the International Society for Cellular Therapy (ISCT) published a position statement proposing that the term "mesenchymal stromal cell" replace "mesenchymal stem cell" in the literature, with the qualifier that any cell described as a "stem cell" should meet a higher bar of demonstrated in vivo self-renewal and differentiation, which most plastic-adherent bone marrow populations do not meet.3
By 2017, the ISCT had reaffirmed the position and 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
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 aspirational; the second is what the data actually show.
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. This is not immune suppression; it is regulated modulation.6
- Support of endogenous tissue repair. By altering the local microenvironment, improving microvascular health, calming chronic inflammation, signaling resident progenitor cells, MSCs may help your own tissue repair machinery work more effectively.
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
"What we now know is that MSCs are functioning as medicinal signaling cells, not stem cells. The 'cure' for tissue defects comes from local cellular repair processes that the MSCs orchestrate."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 lean hard on the "stem cell" framing, particularly those promising regrowth, reversal, or cure, are usually selling on the implicit second meaning, not the technical first one. That's where the patient harm and the FDA enforcement actions tend to concentrate.
A clinic that explicitly uses "mesenchymal stromal cell" or, in patient-friendly language, "cells that signal and modulate, not cells that regenerate", is generally aligned with the current scientific consensus and with FDA-aligned terminology.
05 · How we talk about it
How Boulder Biologics uses each term.
In our clinical letters, on this site, and in patient conversation:
- The biology section calls them mesenchymal stromal cells (MSCs): the ISCT-aligned term.
- In conversation with patients, we sometimes say "stem cells" because it is familiar to the patient and too many new terms can be overwhelming. However, when appropriate we try to educate on the stromal vs stem distinction.
- We describe their clinical effect in functional terms: cell-to-cell signaling, immune modulation, support for your own tissue's repair processes: not regeneration, not replacement, not regrowth.
- In meta-tags and headings, we sometimes include "(stem cells)" parenthetically so patients searching the popular term can find the right page, but the body content uses the scientifically accurate term.
06 · Common questions
Frequently asked.
So are "mesenchymal stem cells" and "mesenchymal stromal cells" the same cells? +
In most everyday usage, yes: they refer to the same cell population (CD105+/CD73+/CD90+/CD45–). The distinction is one of framing, not biology. "Stromal" emphasizes what these cells actually do (signal and modulate); "stem" emphasizes a promise (regenerate and replace) that the human data don't currently support.
If they don't regenerate tissue, what's the clinical benefit? +
The clinical question is whether modulating the local environment, calming chronic inflammation, signaling resident repair machinery, supporting microvascular health, translates into a measurable improvement in symptoms or function. For some indications and some patients, the evidence supports yes. For others, it's preliminary or absent. That's the conversation we have at consultation.
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 surrounding cells, and a substantial chunk of the paracrine effect appears to be vesicle-mediated.8 Whether isolated exosomes administered without their parent cells produce the same effect is an open research question, and one the FDA is actively scrutinizing (see our autologous vs. donor-derived page).
Why not just call them "medicinal signaling cells" like Caplan suggests? +
It's a fair question, and you'll see it in some of the recent literature. The reason it hasn't fully replaced "stromal" is mostly inertia, "MSC" as a shorthand is too well-established in the scientific literature, regulatory documents, and clinical-trial registries to easily replace. "Stromal" remains the most-used compromise: more accurate than "stem," more searchable than "medicinal signaling."
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;20:345–359.e5.
- Murphy MB, Moncivais K, Caplan AI. Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine. Exp Mol Med. 2013;45: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. MSCs: 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. Nano Lett. 2019;19(6):3422–3431.
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