The research, sorted by how much it can tell you

Level 1 — laboratory characterization (no patients)

The starting point is cell biology. Dezawa and colleagues reported in 2010 that a small fraction of adult human mesenchymal cells, marked by SSEA-3, tolerate stress and can differentiate into multiple tissue types. These "Muse" cells are the subject of everything that follows.

1. Dezawa lab, 2010 (PNAS). Describes Muse cells (multilineage-differentiating stress-enduring cells), a small SSEA-3-positive subpopulation found in adult human mesenchymal tissue and culture. Limits: Laboratory characterization only; no patients were involved.
   Kuroda Y, Kitada M, Wakao S, … Dezawa M. Unique multipotent cells in adult human mesenchymal cell populations. Proc Natl Acad Sci USA. 2010;107(19):8639-43. PubMed 20421459

Level 2 — animal model

Before any human study, the question was whether intravenously given Muse cells reach injured tissue at all. In rabbits, they did, through S1P–S1PR2 signaling. An animal mechanism is a hypothesis for humans, not a result in humans.

1. Yamada et al., 2018 (Circulation Research). In a rabbit model, intravenously given Muse cells accumulated in injured heart tissue through the sphingosine-1-phosphate (S1P)–S1PR2 signaling axis. Limits: Animal study. A homing mechanism shown in rabbits does not establish what happens in people.
   Yamada Y, Wakao S, Kushida Y, et al. S1P–S1PR2 axis mediates homing of Muse cells into damaged heart for long-lasting tissue repair and functional recovery after acute myocardial infarction. Circ Res. 2018;122(8):1069-83. PubMed 29475983

Level 3 — first-in-human and small randomized trials

Two Japanese studies of the CL2020 product form the human Muse-cell evidence to date. Note the sample sizes: three participants, then 35. The randomized stroke trial reported adverse events in nearly every participant in both arms and one grade-4 event in the CL2020 arm; the authors describe their efficacy finding as possible and in need of larger confirmation.

1. Noda et al., 2020 (Circulation Journal). First-in-human report of CL2020, an allogeneic Muse-cell product, given intravenously to three patients after a heart attack, with 12 weeks of follow-up. Limits: Three participants, no control group. A report this small can only describe early observations, not establish an effect.
   Noda T, Nishigaki K, Minatoguchi S. Safety and efficacy of human Muse cell-based product for acute myocardial infarction in a first-in-human trial. Circ J. 2020;84(7):1189-92. PubMed 32522904
2. Niizuma et al., 2023 (J Cereb Blood Flow Metab). Randomized, double-blind trial: 25 participants received CL2020 and 10 received placebo, 14–28 days after an ischemic stroke, followed for 52 weeks. Limits: Small trial. Adverse events were reported in 96% of the CL2020 group and 100% of the placebo group; adverse reactions in 28% versus 10%, including one grade-4 event. The authors describe the result as a possible effect that needs larger confirmation.
   Niizuma K, Osawa SI, Endo H, et al. Randomized placebo-controlled trial of CL2020, an allogenic Muse cell-based product, in subacute ischemic stroke. J Cereb Blood Flow Metab. 2023;43(12):2029-39. PubMed 37756573

Level 3, continued — mesenchymal-cell cardiology trials

Two older trials used mesenchymal stem cells (not Muse cells) given intravenously in cardiology settings. They are often quoted for their adverse-event data, which was similar between cell and placebo groups at the doses studied. Both are small and their efficacy measures were exploratory or phase 1/2.

1. Hare et al., 2009 (JACC). Dose-ranging trial (53 participants) of intravenous allogeneic bone-marrow MSCs after a heart attack; the primary endpoint was the rate of adverse events over six months, which was similar between groups. Limits: Designed to study adverse events, not to prove benefit; the efficacy measures were exploratory.
   Hare JM, Traverse JH, Henry TD, et al. A randomized, double-blind, placebo-controlled, dose-escalation study of intravenous adult human mesenchymal stem cells (Prochymal) after acute myocardial infarction. J Am Coll Cardiol. 2009;54(24):2277-86. PubMed 19958962
2. Bartolucci et al., 2017 (RIMECARD, Circulation Research). Phase 1/2 trial, 15 participants per arm, of intravenous umbilical-cord MSCs versus placebo in stable heart failure, with 12 months of follow-up. Limits: Thirty people in total; phase 1/2 trials are hypothesis-generating and are not designed to change clinical practice on their own.
   Bartolucci J, Verdugo FJ, González PL, et al. Safety and efficacy of the intravenous infusion of umbilical cord mesenchymal stem cells in patients with heart failure: a phase 1/2 randomized controlled trial (RIMECARD). Circ Res. 2017;121(10):1192-1204. PubMed 28974553

Level 4 — the large trial that did not meet its endpoint

Any honest summary has to include the opposite result. The largest cell-therapy trial in heart failure, with 565 participants, missed its primary endpoint. Early signals in small trials routinely shrink when tested at scale, which is why the whole field is described as investigational.

1. Perin et al., 2023 (DREAM-HF, JACC). The largest cell-therapy trial in heart failure to date (565 participants) did not meet its primary endpoint. It is a reminder that early signals in small trials often shrink or disappear in larger ones.
   Perin EC, Borow KM, Henry TD, et al. Randomized trial of targeted transendocardial mesenchymal precursor cell therapy in patients with heart failure. J Am Coll Cardiol. 2023;81(9):849-63. PubMed 36858705

Three questions to bring to any consultation

1. Which study supports this specific procedure for this specific part of the body — and was it in humans?
2. What adverse events were reported in that study, and how many people were in it?
3. What would a realistic range of responses look like, including no change?

For a different cut of the same literature — the six studies in one list with a "how to read a research page" checklist — see the research summary on StemCellReviewer.com.

Reviewed for medical accuracy by Dr. Charles Pereyra, MD, Medical Director, Springs Rejuvenation (bio).

Stem cell and exosome procedures are investigational. The studies discussed on these pages are early, mostly small, and individual responses vary. Nothing here is medical advice; please consult a licensed physician about your own situation.