Episode 186: Mari Dezawa discusses her discovery of MUSE cells and the role of stem cells in regenerative medicine
STEM-Talk
The Discovery of MUSE Cells in Regenerative Medicine
This chapter delves into the significance of somatic and MUSE cells, highlighting a serendipitous discovery from a research mix-up that unveiled the remarkable properties of MUSE cells. The speaker shares their journey through stem cell research and explores the unique capabilities of MUSE cells in tissue repair and regeneration. The implications of these findings suggest groundbreaking shifts in therapeutic applications for neurodegenerative diseases and cardiovascular recovery.
Today we have Dr. Mari Dezawa, one of the world’s leaders in stem-cell research and regenerative medicine. Mari is a pioneer in this emerging field and is known worldwide for her discovery of MUSE cells, a unique type of stem cell with exciting clinical potential. MUSE is short for Multilineage-Differentiating Stress-Enduring Cells.
The discovery of the MUSE cell in humans has many biological and medical implications, and the human body may have a greater regenerative potential than we might have ever imagined. In collaboration with major national and international institutions, Mari and her colleagues are promoting research on MUSE cell-based regenerative medicine for diseases without definitive treatments. She and her team are also exploring the differences in regenerative capacity between less and more complex animals from the viewpoint of the stem-cell system.
Mari is a professor and chair of the Division of Stem Cell Biology and Histology at Tohoku University School of Medicine. She has published more than 200 papers and is particularly known for her 2010 paper on the mechanisms of MUSE cells. In 2018, she was appointed a fellow of the U.S. National Academy of Inventors and has been the recipient of numerous awards, including the Japanese Government’s Prize for the Commendation for Science and Technology.
Show notes:
[00:04:10] Ken opens the interview by mentioning that although Mari was born in Japan, her family moved to the U.S. when she was only eight months old. Ken asks if it is true that Mari finds it difficult to answer the question of where her hometown is.
[00:05:23] Ken asks Mari how she handled moving so much as a child.
[00:05:52] Ken mentions that Mari’s father was a researcher and asks when she became passionate about research and science.
[00:06:58] Ken mentions that Mari attended the Chiba University School of Medicine and asks what inspired her to go to medical school.
[00:07:19] Ken explains that after Mari earned her medical degree, she attended Chiba University Graduate School of Medicine for her Ph.D. Ken mentions that while Mari was initially a cardiology resident, she later decided to focus on clinical research and became a stem-cell researcher. Ken asks what led her to shift from cardiology to stem-cell research.
[00:08:25] Ken explains that Mari is well-known for her research into the role of stem cells in regeneration and functional recovery of nerve and muscle cells. Ken asks how and when she first became interested in stem cells.
[00:09:56] Ken asks Mari to give a brief overview of stem cells and their significance.
[00:11:18] Ken mentions that Mari remained at Chiba University as a research associate after earning her Ph.D in 1995. She then took a position as an associate professor at Yokohama City University Graduate School of Medicine before accepting a position at Kyoto University Graduate School of Medicine as an associate professor in 2003. Ken explains that while at Kyoto, Mari developed methods to induce bone marrow stromal cells to generate neuro and skeletal muscle cells, which play a crucial role in tissue repair and regeneration and are widely studied for their potential to serve as therapeutic agents. Ken asks Mari to give a quick primer on the crucial role these cells play in tissue repair.
[00:13:25] Ken explains that in 2003, a member of Mari’s technical staff at Kyoto asked her whether they should discard some cultured adult rat and human bone marrow mesenchymal stem cells (MSCs) after she had noticed several strange cell clusters. Ken asks Mari to share what happened next and how this set her on the path to the discovery of Multilineage-Differentiating Stress-Enduring Cells.
[00:16:03] Ken asks Mari to elaborate on this story and explain how a mistake led to this incredible discovery.
[00:20:48] Ken explains that in 2008 Mari became professor and chair of the Department of Stem Cell Biology and Histology at Tohoku University Graduate School of Medicine. Then in 2010 she published a paper on the results of her investigations into MUSE cells. Ken asks about this paper and why it was so significant.
[00:25:11] Ken mentions that one of the key characteristics of MUSE cells is their ability to repair organ tissues, and their ability to repair themselves quickly. Ken asks Mari to explain the significance of MUSE cell resilience and self-repair.
[00:26:30] Ken asks Mari how MUSE cells are collected.
[00:28:26] Ken asks Mari about her 2018 paper that looked at the use of MUSE cells in the treatment of acute myocardial infarction.
[00:31:03] Ken explains that stem cells go through cytokine differentiation, a process that can often take several weeks or more to complete. However, Mari uncovered that a simple mechanism could substantially shorten this timeframe, which she reported on in a 2022 paper, titled “Phagocytosing Differentiated Cell-Fragments is a Novel Mechanism for Controlling Somatic Stem Cell Differentiation Within a Short Timeframe.” Ken asks Mari to discuss this paper and its findings
[00:33:51] Ken asks Mari if she sees any potential military applications for MUSE cells.
[00:35:16] Mari explains what exosomes are and how they might be applied in the context of MUSE cells.
[00:36:14] Ken mentions Mari’s report on nasal administration of stem cells titled “Nose-to-Brain Delivery of Human Cells Enhances Structural and Functional Recovery in the Murine Ischemic Stroke Model.” Ken asks Mari to talk about the findings in this paper.
[00:37:34] Ken asks Mari about her paper in development on the use of MUSE cells in the treatment of traumatic brain injury and dementia.
[00:38:54] Ken brings up the issues with models of Alzheimer’s not tending to reflect the reality of the disease in humans and asks Mari what her plans are for applying her research to human trials in Alzheimer’s.
[00:40:21] Ken asks Mari for her thoughts on the use of MSCs and MUSE cells for health span optimization.
[00:42:11] Ken explains that in addition to her university work, Mari also works with a company called MUSE Cell Innovations, which is looking to revolutionize regenerative medicine and longevity through advancements in cellular science. For full disclosure, Ken explains that both he and Mari serve on the scientific advisory board of MUSE Cell Innovations. Ken asks Mari to talk about her work there.
[00:44:13] Ken mentions that in another interview, Mari talked about how her hobbies were a way of balancing her life and career. However, Mari never explained what those hobbies were, so Ken asks her to elaborate.
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