By Vivonyx · Last reviewed: November 2026
Almost every article on this site mentions mesenchymal stem cells, or MSCs. So here's the question underneath all of them: how do researchers think these cells actually work?
The short answer surprises many people. The leading ideas aren't mainly about cells turning into new tissue. They're about cells sending signals. This article walks through the main proposed mechanisms in plain language, and is clear about what's still unproven in people. It's education, not medical advice.
First, what is an MSC?
MSCs are cells that can be grown in the lab from tissues such as bone marrow, fat, and umbilical cord. To make studies comparable, an international cell therapy society set minimum lab criteria: the cells stick to plastic in culture, carry certain surface markers, and can be coaxed into bone, fat, and cartilage cells in a dish [1].
That last point gave MSCs the "stem cell" label. But making bone or cartilage in a dish is not the same as doing it inside the body. One of the scientists who named MSCs, Arnold Caplan, later urged renaming them "Medicinal Signaling Cells," arguing that their main effect is the bioactive factors they release, and that the body's own resident cells build any new tissue [2]. Many researchers also prefer "mesenchymal stromal cells," a reminder that not every cell in the mix behaves like a true stem cell [3][4].
Mechanism 1: Paracrine signaling
"Paracrine" means a cell releases chemical messages that act on cells nearby. Researchers propose this is the main way MSCs act: they release growth factors, cytokines (immune messenger proteins), and other molecules that may influence inflammation and the behavior of surrounding cells [2][4].
One mouse study showed how this might work even when cells don't reach the injured spot. After human MSCs were infused into a vein, most were trapped in the lungs and disappeared within about a day. Yet the trapped cells switched on a gene for an anti-inflammatory protein called TSG-6, and cells with that gene blocked did not show the same benefit in a heart-injury model [5]. That's an animal result, not proof of what happens in people.
Mechanism 2: Extracellular vesicles and exosomes
MSCs also release extracellular vesicles: tiny bubbles of membrane, including exosomes. A review by Phinney and Pittenger describes their cargo as cytokines, growth factors, signaling fats, and genetic messages such as microRNAs [6]. Researchers propose these vesicles could carry part of the cells' signaling effect.
The same review notes that vesicle contents aren't fixed. They change with the tissue the cells came from and the cells around them, which makes quality and consistency a central challenge [6]. The FDA lists exosomes among unapproved regenerative medicine products and warns consumers about them [7].
Mechanism 3: Immunomodulation
"Immunomodulation" means adjusting how the immune system responds. In lab dishes, human MSCs shifted several immune cell types toward a calmer pattern: some T cells made less of the inflammatory signal interferon-gamma, other immune cells made more of the anti-inflammatory signal IL-10, and the share of regulatory T cells rose. Blocking a molecule called prostaglandin E2 reduced these effects [8].
Macrophages, the immune system's clean-up cells, appear to matter too. In a mouse sepsis model, MSCs appeared to reprogram macrophages to make more IL-10, and the benefit disappeared when macrophages were removed [9]. A 2019 expert review calls these anti-inflammatory and immune effects the biggest focus of human MSC trials today [4].
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Mechanism 4: Homing and engraftment, and why most cells don't stay
"Homing" means cells traveling to an injury. "Engraftment" means settling in and staying. The early hope was that MSCs would do both, then rebuild tissue.
Animal tracking studies point the other way. In mice given MSCs by vein, viable cells were found in the lungs for up to 24 hours and then disappeared; none were found alive in other organs. The authors concluded that longer-lasting effects must run through other cells [10]. The TSG-6 study found a similar pattern [5]. This is a big reason the field shifted toward a "signaling" view. It's also why researchers say injected cells may have short-lived effects, though how long effects last in people isn't known.
Mechanism 5: Mitochondrial transfer
Mitochondria are the parts of a cell that make energy. In a mouse lung-injury study, bone marrow MSCs attached to lung lining cells and passed mitochondria to them through tiny channels and vesicles. Energy levels in the lung tissue rose, and cells unable to make those connections didn't show the protective effect [11]. Researchers propose this as one more possible mechanism, but the evidence is mainly from animal and lab models.
Do cells from different tissues act differently?
Yes, at least in the lab. A review comparing MSCs from adult tissues (bone marrow, fat, blood) and newborn tissues (placenta and umbilical cord) found differences in surface markers, growth rate, and immune properties [12]. Cells' surroundings, oxygen levels, and how they're grown can all shift their behavior [12][6]. So "an MSC" isn't one fixed thing, and results from one source or lab method may not carry over to another. Our Wharton's jelly vs. bone marrow article goes deeper on cell sources.
From the lab to people
Galipeau and Sensébé note that advanced MSC trials have often "fallen short of expectations" raised by animal data, and point to differences between pre-clinical research and human studies, including how cells are grown, stored, and dosed [3]. In other words, a mechanism seen in a mouse or a dish doesn't automatically mean a benefit in people. Our knee arthritis research tour shows what human trials have measured so far.
What the FDA says
The FDA says regenerative medicine therapies have not been approved for any orthopedic condition, such as osteoarthritis, back pain, or knee, hip, or shoulder pain [13]. In December 2024, it approved the first MSC therapy, a donor bone marrow MSC product for a serious transplant complication in children (steroid-refractory acute graft-versus-host disease) [14]. The FDA has also received reports of blindness, tumor formation, and infections linked to unapproved products [13]. Our guide Is Stem Cell Therapy FDA Approved? explains what approval means.
What we still don't know
Which mechanism matters most in people. Most evidence comes from lab and animal studies [3][4].
How long any effect lasts, given that most infused cells don't persist [10].
How to measure and standardize cells and vesicles, since they vary by source and lab method [6][12].
Frequently asked questions
Do mesenchymal stem cells turn into new tissue? They can form bone, fat, and cartilage cells in a dish, but researchers now propose their main effect is signaling to the body's own cells rather than becoming new tissue [1][2].
What is paracrine signaling? It's when cells release chemical messages, such as growth factors and cytokines, that act on nearby cells. Researchers propose this is the main way MSCs act [2][4].
What are MSC exosomes? Tiny vesicles released by MSCs that carry proteins, fats, and genetic messages. The FDA lists exosomes among unapproved regenerative medicine products [6][7].
How long do injected MSCs stay in the body? In mouse studies, most cells given by vein were trapped in the lungs and gone within about a day. How long cells last in people depends on many factors and isn't well established [10][5].
Are MSCs FDA-approved for joints? No. The FDA says regenerative medicine therapies have not been approved for any orthopedic condition. Its first approved MSC therapy is for a transplant complication in children [13][14].
Still have questions?
If you'd like help reading a study about how these cells work, email hello@vivonyx.com or use our Ask page. We'll give you a straight answer, including "the research doesn't know yet" when that's the truth.
Related reading
Wharton's Jelly vs. Bone Marrow Stem Cells: What the Research Shows
Is Stem Cell Therapy FDA Approved? Approval Isn't the Whole Story
Educational disclaimer: This article is for general educational purposes only and is not medical advice, diagnosis, or treatment. It does not describe or suggest the treatment, cure, or prevention of any disease or condition. Regulatory status can change; check the cited FDA pages for current information. Talk with a qualified, licensed healthcare professional before making any medical decision.
References
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. PMID: 16923606. https://pubmed.ncbi.nlm.nih.gov/16923606/
Caplan AI. Mesenchymal stem cells: time to change the name! Stem Cells Transl Med. 2017;6(6):1445-1451. PMID: 28452204. https://pubmed.ncbi.nlm.nih.gov/28452204/
Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824-833. PMID: 29859173. https://pubmed.ncbi.nlm.nih.gov/29859173/
Pittenger MF, Discher DE, Péault BM, et al. Mesenchymal stem cell perspective: cell biology to clinical progress. NPJ Regen Med. 2019;4:22. PMID: 31815001. https://pubmed.ncbi.nlm.nih.gov/31815001/
Lee RH, Pulin AA, Seo MJ, et al. Intravenous hMSCs improve myocardial infarction in mice because cells embolized in lung are activated to secrete the anti-inflammatory protein TSG-6. Cell Stem Cell. 2009;5(1):54-63. PMID: 19570514. https://pubmed.ncbi.nlm.nih.gov/19570514/
Phinney DG, Pittenger MF. Concise review: MSC-derived exosomes for cell-free therapy. Stem Cells. 2017;35(4):851-858. PMID: 28294454. https://pubmed.ncbi.nlm.nih.gov/28294454/
U.S. Food and Drug Administration. Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/consumer-alert-regenerative-medicine-products-including-stem-cells-and-exosomes
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood. 2005;105(4):1815-1822. PMID: 15494428. https://pubmed.ncbi.nlm.nih.gov/15494428/
Németh K, Leelahavanichkul A, Yuen PS, et al. Bone marrow stromal cells attenuate sepsis via prostaglandin E2-dependent reprogramming of host macrophages to increase their interleukin-10 production. Nat Med. 2009;15(1):42-49. PMID: 19098906. https://pubmed.ncbi.nlm.nih.gov/19098906/
Eggenhofer E, Benseler V, Kroemer A, et al. Mesenchymal stem cells are short-lived and do not migrate beyond the lungs after intravenous infusion. Front Immunol. 2012;3:297. PMID: 23056000. https://pubmed.ncbi.nlm.nih.gov/23056000/
Islam MN, Das SR, Emin MT, et al. Mitochondrial transfer from bone-marrow-derived stromal cells to pulmonary alveoli protects against acute lung injury. Nat Med. 2012;18(5):759-765. PMID: 22504485. https://pubmed.ncbi.nlm.nih.gov/22504485/
Hass R, Kasper C, Böhm S, Jacobs R. Different populations and sources of human mesenchymal stem cells (MSC): a comparison of adult and neonatal tissue-derived MSC. Cell Commun Signal. 2011;9:12. PMID: 21569606. https://pubmed.ncbi.nlm.nih.gov/21569606/
U.S. Food and Drug Administration. Important Patient and Consumer Information About Regenerative Medicine Therapies. https://www.fda.gov/vaccines-blood-biologics/consumers-biologics/important-patient-and-consumer-information-about-regenerative-medicine-therapies
U.S. Food and Drug Administration. FDA Approves First Mesenchymal Stromal Cell Therapy to Treat Steroid-refractory Acute Graft-versus-host Disease (press announcement, December 18, 2024). https://www.fda.gov/news-events/press-announcements/fda-approves-first-mesenchymal-stromal-cell-therapy-treat-steroid-refractory-acute-graft-versus-host