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Millman Lab

  • Millman Lab SC β cells

    SC-β cells transplanted into a mouse (insulin=green, glucagon=red)

    The major focus of the Millman laboratory is the in vitro production and study of pancreatic insulin-producing β cells from human pluripotent stem cells for use in cellular replacement therapy and drug screening. The rapid rise in the occurrence of diabetes mellitus has garnered much attention in the development of technologies to better study and treat this disease. As diabetes is caused by the destruction or dysfunction of insulin-producing pancreatic β cells, much of this focus has been directed to the generation of human β cells in vitro, for without this capability, further advancement in disease modeling, drug screening, and transplantation are precluded.

    Endocrine Cells from Stem Cells

    Various endocrine cells from stem cells

    Dr. Millman with colleagues developed a 6-step protocol for generating functional pancreatic β cells in vitro from human pluripotent stem cells. These cells, called stem cell-derived β cells (SC-β cells), have similar physiological function of adult β cells as assessed by numerous in vitro and in vivo assays. Upon transplantation, these insulin-producing cells rapidly reverse hyperglycemia in diabetic mice. We are able to generate these cells in highly-scalable suspension culture, producing up to half a billion cells per batch.

    The Millman laboratory is investigating methods to improve the generation, function, and utility of SC-β cells, primarily by using biomedical engineering approaches to introduce and modulate microenvironmental cues that play an important role in β cell development and function. These methods are also being extended to investigate SC-β cells generated from diabetic patients using induced pluripotent stem cells (iPS cells).


    Outline of SC-β cell technology

    Outline of SC-β cell technology

  • Stem Cell Technology for Scalable SC-β Cell Production

    Stem Cell Technology

    The methods found in the Millman laboratory afford the ability to produce large quantities of human pluripotent stem cells and SC-β cells. Cells are grown in scalable suspension culture as clusters approximately the size of an islet in disposable spinner flasks. Up to half a billion cells, of which almost half produce insulin, can be produced per flask using this approach. Suspension culture has the additional advantage of providing a three-dimensional environment to better mimic in vivo development.

    The goal of Millman laboratory is for these cells to one day be used in cell replacement therapy to treat diabetic patients by transplanting these exogenous cells to replace the function lost by the endogenous β cells. We hope to accomplish this through a multidisciplinary approach combining stem cell technology, biomedical engineering approaches, and islet biology.


    Tissue Engineering the Islet Microenvironment

    Tissue Engineering the Islet Microenvironment


    Genome Engineering of Human Pluripotent Stem Cells

    Genome Engineering of Human Pluripotent Stem Cells


    Study of Diabetic Patient-Derived SC-β Cells

    Study of Diabetic Patient-Derived SC-β Cells

  • Publications

    Jiwon Song and Jeffrey R. Millman. Economic 3D-Printing Approach for Transplantation of Stem Cell-Derived β Cells. Biofabrication 9(1), 015002 (2016).

    †Jeffrey R. Millman, Chunhui Xie, Alana van Dervort, Mads Gürtler, Felicia W. Pagliuca, and †Douglas A. Melton. Generation of stem cell-derived β cells from patients with type 1 diabetes. Nature Communications 7, 11463 (2016).

    Arturo J. Vegas, Omid Veiseh, Mads Gürtler, Jeffrey R. Millman, Felicia W. Pagliuca, Andrew R. Bader, Joshua C. Doloff, Jie Li, Michael Chen, Karsten Olejnik, Hok Hei Tam, Siddharth Jhunjhunwala, Erin Langan, Stephanie Aresta-Dasilva, Srujan Gandham, James J. McGarrigle, Matthew A. Bochenek, Jennifer Hollister-Lock, Jose Oberholzer, Dale L. Greiner, Gordon C.Weir, Douglas A. Melton, Robert Langer, Daniel G. Anderson. Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Nature Medicine 22(3), 306-11 (2016).

    **Felicia W. Pagliuca, **Jeffrey R. Millman, **Mads Gurtler, Michael Segel, Alana Van Dervort, Jennifer Hyoje Ryu, Quinn P. Peterson, Dale Greiner, Douglas A. Melton. Generation of Functional Human Pancreatic β Cells In Vitro. Cell 159, 428-39 (2014).

    Siniša Hrvatin, Charles W. O’Donnell, Francis Deng, Jeffrey R. Millman, Felicia W. Pagliuca, Philip DiIorio, Alireza Rezania, David K. Gifford, Douglas A. Melton. Differentiated Human Stem Cells Resemble Fetal, Not Adult β Cells. Proceeding of the National Academy of Sciences 111(8), 3038-43 (2014).

    **Daryl E. Powers, **Jeffrey R. Millman, Michael Rappel, Clark K. Colton. Accurate control of oxygen level in cells during culture on silicone rubber membranes with application to stem cell differentiation. Biotechnology Progress 26(3), 805-18 (2010).

    **Jeffrey R. Millman, **Jit Hin Tan, Clark K. Colton. The effects of low oxygen on self-renewal and differentiation of embryonic stem cells. Current Opinions in Organ Transplantation 14(6), 694-700 (2009).

    **Renita Horton, **Jeffrey R. Millman, Clark K. Colton, Debra Auguste. Engineering microenvironments for embryonic stem cell differentiation to cardiomyocytes. Regenerative Medicine 4(5), 721-32 (2009).

    Daryl E. Powers, Jeffrey R. Millman, Ryan B. Huang, Clark K. Colton. Effects of oxygen on mouse embryonic stem cell growth, phenotype retention, and cellular energetics. Biotechnology and Bioengineering 101, 241-54 (2008).

    Jeffrey R. Millman, Ketan H. Bhatt, Brian G. Prevo, Orlin D. Velev. Anisotropic particle synthesis in dielectrophoretically controlled microdroplet reactors. Nature Materials 4, 98-102 (2005).

    **Co-first authors
    †Co-corresponding author

    Patents

    Clark K. Colton, Daryl E. Powers, Jeffrey R. Millman. Methods and Compositions for Enhanced Differentiation from Embryonic Stem Cells. Patent No. 9,029,147. Issued May 12, 2015.

    Clark K. Colton, Jeffrey R. Millman. Methods and compositions for increased safety of stem cell-derived populations. Patent No. 9,388,381. Issued July 12, 2016.

    Clark K. Colton, Amanda R. DiIenno, Jeffrey R. Millman. Method for Differentiating Human Embryonic Stem Cells into β-cells for the Treatment of Type 1 Diabetes. Patent No. 9,447,378. Issued September 20, 2016.

    Jeffrey R. Millman, Jiwon Song. 3D-PRINTED SCAFFOLD DEVICE FOR CELL TRANSPLANTATION. Patent Application No. 62410760. October 20, 2016

    Douglas A. Melton, Jeffrey R. Millman. METHODS FOR GENERATING STEM CELL-DERIVED β CELLS AND USES THEREOF. Patent Application No. 62/093,999. Filed December 18, 2015.

    Douglas A. Melton, Jeffrey R. Millman. METHODS FOR GENERATING STEM CELL-DERIVED β CELLS AND USES THEREOF. Patent Application No. 14/975,255. Filed December 18, 2015.

    Douglas A. Melton, Jeffrey R. Millman, Mads Gurtler. METHODS FOR GENERATING AUGMENTED STEM CELL-DERIVED β CELLS AND USES THEREOF. Patent Application No. 62/093,942. Filed December 18, 2015.

    Jeffrey R. Millman, Quinn P. Peterson, Douglas A. Melton. SC-α CELLS AND METHODS FOR GENERATING AND USING THE SAME. Provisional Patent Application No. 62/093,942. Filed September 25, 2015.

    Quinn P. Peterson, Felicia W. Pagliuca, Douglas A. Melton, Jeffrey R. Millman, Michael Segel, Mads Gurtler. SC-β Cells and Compositions and Methods for Generating the Same. Patent Application No. 14/684,129. Filed April 10, 2015.

  • Group Picture

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    Laboratory Contact Information

    Office Location
    838 Southwest Tower (Medical campus)

    Mailing Address
    660 S. Euclid Ave.
    Campus Box 8127
    St. Louis, MO 63110

    Phone: (314) 362-3347
    Fax: (314) 362-7641


    Jeffrey R. Millman, Ph.D.
    Principal Investigator

    Jeffrey R. Millman, Ph.D.
    Assistant Professor of Medicine and Biomedical Engineering

    jmillman@dom.wustl.edu

    Dr. Millman received his Ph.D. in Chemical Engineering from the Massachusetts Institute of Technology in 2011, where he studied the effects of controlled oxygen exposure on stem cell differentiation with Dr. Clark Colton. He completed his postdoctoral research fellowship at Harvard University with Dr. Douglas Melton, developing methods to generate functional pancreatic insulin-producing β cells from human stem cells, and received a Harvard Stem Cell Institute Postdoctoral Fellowship. Dr. Millman joined the Department of Medicine faculty at Washington University in St. Louis in 2015.


    Jiwon Song
    Jiwon Song, B.S.
    Research Assistant

    jsong@dom.wustl.edu

    Jiwon joined the Millman Lab in September 2015 after receiving her B.S. degree in Biomedical Engineering from Washington University in St. Louis. She hopes to attend graduate school in the near future. When she is not working in the lab, Jiwon enjoys swimming, playing the cello, and exploring new parts of the city.


    Nathaniel Hogrebe, PhD
    Nathaniel Hogrebe, Ph.D.
    Postdoctoral Research Fellow

    nhogrebe@wustl.edu

    Nathaniel earned his bachelor’s degree in Chemical Engineering from the University of Dayton and completed his PhD in Biomedical Engineering at The Ohio State University. His doctoral research focused on the importance of insoluble cues from the cellular microenvironment on certain cell behaviors, such as human mesenchymal stem cell differentiation. He joined the Millman Lab in November 2016 with the hopes of using these skills to help improve SC-β cell differentiation and assist in the tissue engineering of pancreatic islets. Outside of the lab, Nathaniel has a good time participating in a variety of sports such as tennis and ice hockey, playing the piano, and enjoying the outdoors.


    Stephanie Shahan

    Stefanie Shahan, B.S.
    Master’s Student

    stshahan@wustl.edu

    Stefanie was welcomed to the Millman Lab in May 2016 having graduated with a B.S. degree in Biomedical Engineering from Washington University in St. Louis. She is now moving forward in pursuit of her M.S. in Biomedical Engineering. Her hobbies include running, cooking, and reading.

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    Leonardo Velazco-Cruz, B.S.
    Leonardo Velazco-Cruz, B.S.
    Doctoral Student

    leonardo@wustl.edu

    Leonardo received his B.S. degree in Biology from California State University, Fresno. He joins the Millman Lab on January 2017 as a predoctoral candidate seeking to generate advancements in stem cell technology and diabetes pathogenesis. Leonardo’s leisure time include rock climbing, running, and trying new foods.

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    Kristina Maxwell
    Kristina Maxwell, B.S.
    Doctoral Student

    kgmaxwell@wustl.edu

    Kristina earned a B.S. in Biomedical Engineering from the University of Arkansas. She was accepted to the Biomedical Engineering PhD program at Washington University in St. Louis in the next fall and started a rotation in the Millman Lab in January 2017. She is interested in the development of stem cell technology to treat and model diabetes using SC-β cells. When not in the lab, Kristina enjoys participating in intramural sports with her classmates, running in Forest Park, and summer musicals at the Muny.


    Sara Arfania
    Sara Arfania
    Undergraduate Researcher

    saraarfania@wustl.edu

    Sara is an undergraduate student working toward a B.S. in Biomedical Engineering and a minor in Psychological & Brain Sciences at Washington University in St. Louis. On campus, she is involved in a variety of organizations, including the Executive Board of WUSTL’s Relay for Life Steering Committee. She enjoys reading, exploring the outdoors, and cooking. She joined the Millman Lab in January of 2017 and hopes to attend medical school in the future.


    Anurima Sharma
    Anurima Sharma
    Undergraduate Researcher

    anurimasharma@wustl.edu

    Anurima is an undergraduate student majoring in Biomedical Engineering and minoring in Computer Science at Washington University in St. Louis. She is very involved with the Society of Women Engineers, Ashoka (a South Asian Cultural group) and Wash U Garba (an Indian Dance Team). She is also going to be a Residential Advisor for the 2017-2018 and 2018-2019 school years. She began working in the Millman Lab in February of 2017.


    Currently seeking research assistants, graduate students, and research fellows.

    Undergraduates are also encouraged to enquire.


  • The Millman lab welcomes Anurima Sharma to the group as an undergraduate researcher!
    February, 2017

    The Millman lab welcomes Leonardo Velazco-Cruz to the group as a Division of Biology & Biomedical Sciences Ph.D. student!
    January 23, 2017

    The Millman lab welcomes Kristina Maxwell to the group as a Biomedical Engineering Ph.D. rotation student and Sara Arfania as an undergraduate researcher!
    January 16, 2017

    Research from the Millman laboratory highlighted by NIH NIDDK
    December 27, 2016
    Making beta cells from people with type 1 diabetes

    Published new article showcasing a 3D-printing approach for transplantation of stem cell-derived β-like cells
    December 1, 2016

    We congratulate Jiwon Song on her first first-authorship publication that just came out in Biofabrication entitled “Economic 3D-printing approach for transplantation of human stem cell-derived β-like cells” demonstrating a 3D-printing approach for fabricating a macroporous and retrievable transplantation device. This research could someday be used to deliver stem cell-derived β-like cells for cell replacement therapy in diabetes.

    WUSTL Endocrinology Article

    The Millman lab welcomes Dr. Nathaniel Hogrebe to the group as a postdoctoral research fellow!
    November 1, 2016.

    Dr. Millman issued a new patent entitled “Method for differentiating human embryonic stem cells into β-cells for treatment of type I diabetes”, patent number 9,447,378.
    September 20, 2016.

    Dr. Millman issued a new patent entitled “Methods and compositions for increased safety of stem cell-derived populations”, patent number 9,388,381.
    July 12, 2016.

    The Millman lab welcomes Stefanie Shahan to the group as a Biomedical Engineering M.S. student!
    June 6, 2016.

    Published new article generating stem cell-derived β cells from Type 1 diabetic patients
    May 10, 2016

    We have published an article with Harvard University colleagues in Nature Communications entitled “Generation of stem cell-derived β-cells from patients with type 1 diabetes” demonstrating extension of our prior method for making stem cell-derived β cells to diabetic patients.  This research will open up the potential for autologous cell replacement therapy in diabetes and the further development of diabetes disease modeling for drug screening.

    WUSTL Press Release
    St. Louis Public Radio interview with Dr. Jeffrey Millman
    Link to the Report

    Encapsulation of stem cell-derived beta cells controls blood glucose in immune-competent mice
    January 25, 2016

    Dr. Jeffrey Millman was co-author on a report published in Nature Medicine entitled “Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice”.

    WUSTL Endocrinology Article
    MIT Press Release
    Fox News Article
    US News & World Report Article
    Link to the Report

    Missouri Researcher Spotlight of Dr. Jeffrey Millman’s research is in the October 2015 Missouri Cures Education Foundation newsletter
    October 31, 2015

    Missouri Cures Education Foundation website

    Semma Therapeutics founded based on technology Dr. Jeffrey Millman developed with colleagues at Harvard University.
    March 24, 2015

    Semma Therapeutic press release
    Semma Therapeutics website

    Dr. Jeffrey Millman was interviewed in an article published by The Pharmaceutical Journal entitled “Making β cells in the laboratory”.
    February 10, 2015

    The Pharmaceutical Journal article

    Dr. Jeffrey Millman’s research making stem cell-derived β cells was named one of the top 10 breakthroughs of 2014 by Science Magazine
    December 19, 2014

    Science Magazine Article

    Production of functional stem cell-derived β cells from human stem cells
    October 9, 2014

    Dr. Jeffrey Millman was co-first author with colleagues at Harvard University in a report published in Cell entitled “Generation of Functional Human Pancreatic β Cells In Vitro” demonstrating a strategy for producing functional stem cell-derived β cells from human embryonic stem cells and induced pluripotent stem (iPS) cells.

    CBS Evening News report
    The World Tonight-BBC Radio 4 interview with Dr. Jeffrey Millman
    The Washington Post article
    Harvard University Press Release