The Science Behind Regeneration

Who Discovered Dezawa Muse Cells? The Story of Mari Dezawa, MD, PhD

Quick Answer

Dezawa Muse cells were discovered in 2010 by Professor Mari Dezawa, MD, PhD, at Tohoku University Graduate School of Medicine in Japan. The formal discovery was published in the Proceedings of the National Academy of Sciences (PNAS) by Kuroda Y, Kitada M, Wakao S, and colleagues, with Professor Dezawa as the principal investigator. The name "Dezawa" attached to these cells honors her role as the researcher who first identified, isolated, and characterized them. She remains Professor and Chair of the Department of Stem Cell Biology and Histology at Tohoku University today.

Who is Professor Mari Dezawa?

Professor Mari Dezawa, MD, PhD, is one of the world's foremost researchers in stem cell biology and regenerative medicine. She holds the chair of the Department of Stem Cell Biology and Histology at Tohoku University Graduate School of Medicine in Sendai, Japan, one of the country's most respected research universities. Her career has produced more than 200 peer-reviewed publications, and she is recognized internationally for a single defining contribution: the discovery and characterization of Multilineage-differentiating Stress-Enduring (Muse) cells.

The discovery did not happen overnight. It was the product of more than a decade of work tracing back to an unexpected laboratory observation, methodical investigation, and a willingness to pursue a finding that did not fit neatly into what researchers at the time believed about adult stem cells.

Understanding that path, and the researcher who walked it, gives the science a context that matters for anyone considering Muse cell therapy.

Educational background and early career

Professor Dezawa earned her MD from Chiba University School of Medicine and completed her PhD at Chiba University Graduate School of Medicine in 1995. She began her clinical training as a cardiology resident, gaining direct patient experience before committing fully to laboratory research. That dual foundation, clinical medicine combined with rigorous basic science, shaped the way she approached regenerative biology throughout her career.

After completing her doctorate, she remained at Chiba University as a research associate, then moved to Yokohama City University Graduate School of Medicine. In 2003, she joined Kyoto University Graduate School of Medicine as an associate professor. It was during her time at Kyoto that the observation occurred that would define the next two decades of her research.

In 2008, she was appointed Professor and Chair of the Department of Stem Cell Biology and Histology at Tohoku University Graduate School of Medicine, a position she has held since. The laboratory she chairs has continued to be the primary site of Muse cell research.

The observation that started everything

The discovery of Muse cells did not begin with a planned experiment designed to find a new cell type. It began in 2003, at Kyoto University, with a question a laboratory staff member almost did not ask.

The lab was culturing human bone marrow mesenchymal stem cells (MSCs) as part of ongoing research. During routine maintenance, a staff member noticed that some of the cultures were developing what appeared to be unusual cell clusters. The cultures were old, the conditions were not ideal, and the natural instinct was to discard them and start fresh. Instead, the staff member brought the observation to Professor Dezawa and asked whether to proceed.

Professor Dezawa chose to investigate. The decision to look more closely, rather than discard, opened the door to one of the more significant findings in adult stem cell research in the past two decades.

The clusters were not a contaminant or an artifact of poor culture conditions. They represented a small population of cells within the mesenchymal stem cell preparation that were surviving conditions hostile enough to kill everything around them. That survival, under prolonged enzymatic stress and nutrient deprivation, became the central property the research team would spend years characterizing.

The methodology behind the 2010 discovery

When Dezawa and her team set out to study these stress-surviving cells systematically, they needed a reproducible method to isolate them. The approach they developed was deliberately harsh: human bone marrow MSCs and dermal fibroblasts were subjected to long-term trypsin incubation, extending over 16 hours, without nutrients. Most cells died under these conditions. A small fraction survived.

The surviving cells expressed the surface marker SSEA-3 (Stage-Specific Embryonic Antigen 3), a protein associated with pluripotency in embryonic tissue. Finding SSEA-3 expression in cells isolated from adult mesenchymal tissue was unexpected. Pluripotency markers in adult cells had not been described in this context before.

Further investigation revealed that these cells, despite being isolated from adult tissue without any genetic modification, could differentiate into cells representative of all three germ layers: ectoderm, mesoderm, and endoderm. That is the same broad capacity as embryonic stem cells and induced pluripotent stem cells (iPSCs), the two most-studied pluripotent populations at the time. The difference was that these adult-derived cells did not require any genetic reprogramming to achieve it, and in the published safety studies that followed, they did not form teratomas, the tumors that have constrained the clinical application of embryonic and iPSC-based therapies.

The cells also demonstrated robust self-renewal capacity across multiple generations in culture, meaning the pluripotency marker expression and differentiation ability were retained over time rather than fading with repeated passaging.

The team named the cells Multilineage-differentiating Stress-Enduring cells, and the acronym Muse captured both defining properties in a single word.

The 2010 PNAS publication

The formal discovery was published in the Proceedings of the National Academy of Sciences of the United States of America in 2010. PNAS is one of the most widely cited scientific journals in the world, spanning all disciplines of science. Publication in PNAS reflects a standard of peer review and significance that places the Muse cell discovery among the most scrutinized findings in adult stem cell biology.

The full citation is:

Kuroda Y, Kitada M, Wakao S, Nishikawa K, Tanimura Y, Dezawa M, et al. (2010). Unique multipotent cells in adult human mesenchymal cell populations. Proceedings of the National Academy of Sciences USA, 107(19):8639–8643. DOI: 10.1073/pnas.0911647107

Professor Dezawa is listed as the principal investigator. The paper describes the isolation, characterization, and pluripotency testing of Muse cells, and establishes the SSEA-3 surface marker as the defining identification tool. It also documents their differentiation capacity across germ layers from a single cell, a critical finding for any claim of true pluripotency.

A correction to this paper was published in PNAS in 2014 (DOI: 10.1073/pnas.1408449111), which updated a figure without altering the central findings or conclusions of the original work.

What made the discovery significant

To understand why the 2010 paper mattered, it helps to know what was believed about adult stem cells at the time. The prevailing consensus was that pluripotency, the ability to become any of the body's cell types, was a property of embryonic cells. Adult stem cells were understood to be multipotent at best, meaning they could differentiate into a limited range of related tissue types. Mesenchymal stem cells, for example, could reliably produce bone, cartilage, and fat, but their range did not extend much further.

The Muse cell findings challenged that boundary directly. They described a population of cells isolated from adult human tissue, without any genetic manipulation, that behaved more like embryonic cells in their differentiation range than like the adult stem cells they were found alongside. The cells were not engineered; they existed naturally. They simply had not been identified before because standard cell culture protocols did not include the stress conditions that made them visible.

The absence of teratoma formation in safety testing added a second layer of significance. The inability to safely transplant undifferentiated pluripotent cells without tumor risk had been one of the primary obstacles to clinical application of embryonic stem cells and iPSCs. A naturally occurring pluripotent cell type that did not carry that risk represented a genuinely different category of tool for regenerative medicine research.

Subsequent research and the road to clinical trials

Following the 2010 paper, research expanded rapidly. A 2011 paper by Wakao, Kuroda, Ogura, Shigemoto, and Dezawa published in Cells (1(4):1045–1060) described the regenerative contributions of Muse cells within mesenchymal stem cell populations, clarifying that much of what had been attributed to MSC populations in earlier research may have been driven by the Muse cell fraction within them.

A 2011 paper in PNAS extended the findings further, reporting that Muse cells are the primary source of induced pluripotent stem cells (iPSCs) when fibroblasts are subjected to standard iPSC reprogramming protocols, suggesting a deeper connection between naturally occurring Muse cells and the artificially generated iPSC populations that had dominated stem cell research through the mid-2000s.

Over the following years, independent research groups across Japan, Europe, and North America replicated and expanded the core findings. The homing mechanism, the S1P-S1PR2 receptor system that directs Muse cells to injury sites after intravenous infusion, was characterized. The immune privilege profile, the HLA-G and IDO expression pattern that allows allogeneic Muse cells to avoid immune rejection without immunosuppressive drugs, was documented in published studies.

Life Science Institute, Inc. (LSII), a subsidiary of the Mitsubishi Chemical Group, developed a clinical-grade Muse cell product called CL2020 for investigational use. LSII conducted Phase I and Phase II clinical trials in Japan across several indications, including acute myocardial infarction, subacute ischemic stroke, spinal cord injury, amyotrophic lateral sclerosis, and epidermolysis bullosa. The stroke trial was a randomized, double-blind, placebo-controlled design. Results across these trials contributed to the body of evidence that Dezawa Muse cell research moved from laboratory curiosity to structured clinical investigation. See What conditions are Dezawa Muse cells being studied for? for a detailed review of that trial data.

Professor Dezawa's recognition and current role

Professor Dezawa's work has been recognized at both national and international levels. In 2011, she received the Commendation for Science and Technology from Japan's Minister of Education, Culture, Sports, Science and Technology, Research Category, one of the country's highest honors for scientific contribution. In 2018, she was appointed a Fellow of the National Academy of Inventors (NAI) in the United States, a designation that recognizes researchers whose inventions have made a tangible and significant impact in science and technology.

She has published more than 200 peer-reviewed papers spanning stem cell biology, neural regeneration, and regenerative medicine. Her laboratory at Tohoku University continues active research into Muse cell mechanisms and applications.

Professor Dezawa also serves on the scientific advisory board of MuseCell Innovations, the company that holds the global licensing rights to authentic Dezawa Muse cell products for clinical and research applications. Her advisory role connects the foundational laboratory science directly to the quality standards applied in licensed clinical use.

Why the name "Dezawa" matters

In scientific nomenclature, attaching a researcher's name to a discovery is not routine. It is a form of recognition that the work was foundational enough to define a category. The cells are formally called Muse cells in the published literature, but the common usage of "Dezawa Muse cells" reflects the scientific community's acknowledgment that the characterization, the isolation method, the naming, and the subsequent research program that made clinical application possible all trace back to her laboratory.

For a patient evaluating Muse cell therapy, that lineage matters. When a provider references "Dezawa Muse cells," the name is a pointer to a specific, documented, peer-reviewed body of work. It is not a marketing category. The research it references is publicly available, extensively cited, and subject to independent replication by researchers with no financial stake in the outcome.

The distinction between authentic Dezawa Muse cell products, which are produced under licensed manufacturing standards and verified by SSEA-3 marker testing, and generic claims of "stem cell therapy" is discussed in detail at Authentic Dezawa vs. generic stem cell clinics.

A discovery that almost did not happen

The story of Muse cell discovery is also a reminder of how scientific progress actually moves. The observation that started everything was a question about whether to discard an imperfect cell culture. The methodology that isolated the cells was a stress protocol - extended enzyme treatment without nutrients - that was, in some sense, an accident of the conditions researchers already knew could damage cells. The finding that a small subpopulation survived where everything else died was only significant because someone decided to ask why.

Professor Dezawa's contribution was not just the technical work of characterizing SSEA-3+ cells from mesenchymal preparations. It was the scientific judgment to recognize that an anomaly in a cell culture was worth understanding rather than discarding. That judgment, sustained across the years of work between 2003 and the 2010 publication, is what produced the foundation that clinical Muse cell research now stands on.

Key publications and sources

  • Kuroda Y, Kitada M, Wakao S, Nishikawa K, Tanimura Y, Dezawa M, et al. (2010). Unique multipotent cells in adult human mesenchymal cell populations. Proceedings of the National Academy of Sciences USA, 107(19):8639–8643. DOI: 10.1073/pnas.0911647107
  • Wakao S, Kuroda Y, Ogura F, Shigemoto T, Dezawa M. (2012). Regenerative effects of Mesenchymal Stem Cells: Contribution of Muse cells, a novel pluripotent stem cell type. Cells, 1(4):1045–1060.
  • Wakao S, Kitada M, Kuroda Y, Shigemoto T, Matsuse D, Dezawa M, et al. (2011). Multilineage-differentiating stress-enduring (Muse) cells are a primary source of induced pluripotent stem cells in human fibroblasts. Proceedings of the National Academy of Sciences USA, 108(24):9875–9880. DOI: 10.1073/pnas.1100816108
  • Dezawa M. (2016). Muse cells provide the pluripotency of mesenchymal stem cells: direct contribution of Muse cells to tissue regeneration. Cell Transplantation, 25(5):849–861. DOI: 10.3727/096368916X690881
  • Life Science Institute, Inc. (LSII) - Mitsubishi Chemical Group. CL2020 Phase II clinical trial program, Japan.
  • Department of Stem Cell Biology and Histology, Tohoku University Graduate School of Medicine. Professor greeting and research overview: http://www.stemcells.med.tohoku.ac.jp/english/
  • IHMC STEM-Talk, Episode 186: Mari Dezawa discusses her discovery of MUSE cells and the role of stem cells in regenerative medicine. https://www.ihmc.us/stemtalk/episode-186/
Important: This article is educational and does not constitute medical advice. Dezawa Muse cell therapy has not been evaluated by the U.S. FDA and is not intended to diagnose, treat, cure, or prevent any disease. Outcomes vary by individual. Discuss any treatment decisions with a licensed physician.

Frequently asked questions

Who discovered Dezawa Muse cells?

Professor Mari Dezawa, MD, PhD, and her research team at Tohoku University Graduate School of Medicine in Japan. The discovery was formally published in 2010 in the Proceedings of the National Academy of Sciences.

When were Muse cells discovered?

The PNAS paper formally describing Muse cells was published in 2010. The laboratory observation that initiated the investigation dates to 2003, when an unexpected cell cluster in a bone marrow mesenchymal stem cell culture at Kyoto University prompted Professor Dezawa to investigate what those cells were and why they survived stress conditions that killed the surrounding population.

What journal published the original Muse cell discovery?

The Proceedings of the National Academy of Sciences of the United States of America (PNAS), 2010, volume 107, pages 8639–8643. The lead authors are Kuroda, Kitada, Wakao, and colleagues, with Professor Dezawa as the principal investigator. The DOI is 10.1073/pnas.0911647107.

What is Professor Mari Dezawa's current position?

Professor and Chair of the Department of Stem Cell Biology and Histology at Tohoku University Graduate School of Medicine in Sendai, Japan. She also serves on the scientific advisory board of MuseCell Innovations, the global licensor of authentic Dezawa Muse cell products.

What awards has Professor Dezawa received?

She received the Commendation for Science and Technology from Japan's Minister of Education, Culture, Sports, Science and Technology in 2011. In 2018, she was appointed a Fellow of the National Academy of Inventors (NAI) in the United States. Her work has been published in leading journals including Nature, Cell, and PNAS, and has been cited across more than 200 peer-reviewed papers.

How did the Muse cell discovery happen?

In 2003, a staff member in Professor Dezawa's laboratory at Kyoto University noticed unusual cell clusters in bone marrow mesenchymal stem cell cultures and asked whether to discard them. Rather than discard, Dezawa investigated. Her team found that a small fraction of cells survived harsh stress conditions (prolonged trypsin exposure without nutrients) that killed the rest. These surviving cells expressed SSEA-3, a pluripotency marker, and could differentiate into all three germ layers without genetic modification. That finding became the basis of the 2010 PNAS publication.

Has the 2010 Muse cell finding been independently replicated?

Yes. More than 200 peer-reviewed papers from independent research groups have validated, extended, or applied the original Muse cell findings since 2010. Life Science Institute (Mitsubishi Chemical Group) has conducted Phase II clinical trials in Japan using a licensed Muse cell product across multiple indications including stroke and myocardial infarction.

Questions about Dezawa Muse cell therapy?

Dr. Capasso offers a complimentary consultation to review your health history, answer your questions, and provide a clear assessment of whether regenerative therapies are appropriate for your situation.

Book a Consultation