Jeffrey R. Millman, Ph.D.

Assistant Professor
Internal Medicine
Endocrinology/Metabolism
Biomedical Engineering

Developmental, Regenerative and Stem Cell Biology Program
Molecular Cell Biology Program

  • 314-362-3268

  • 8127

  • 838 Southwest Tower

  • jmillman@dom.wustl.edu

  • http://endo.wustl.edu/millman-lab/

  • @JeffreyRMillman

  • stem cells, diabetes, pluripotency, pancreas, organoids, tissue engineering, ips cells, disease modeling

  • 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.

Research Abstract:

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.

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).

Selected Publications:

Generation of stem cell-derived β-cells from patients with type 1 diabetes. **Millman JR, Xie C, Van Dervort A, Gürtler M, Pagliuca FW, **Melton DA. Nat Commun. 2016 May 10;7:11463. doi: 10.1038/ncomms11463. PMID: 27163171.
**co-senior author

Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice. Vegas AJ, Veiseh O, Gürtler M, Millman JR, Pagliuca FW, Bader AR, Doloff JC, Li J, Chen M, Olejnik K, Tam HH, Jhunjhunwala S, Langan E, Aresta-Dasilva S, Gandham S, McGarrigle JJ, Bochenek MA, Hollister-Lock J, Oberholzer J, Greiner DL, Weir GC, Melton DA, Langer R, Anderson DG. Nat Med. 2016 Mar;22(3):306-11. doi: 10.1038/nm.4030. Epub 2016 Jan 25. PMID: 26808346.

Generation of functional human pancreatic β cells in vitro. ##Pagliuca FW, ##Millman JR, Gürtler M, Segel M, Van Dervort A, Ryu JH, Peterson QP, Greiner D, Melton DA. Cell. 2014 Oct 9;159(2):428-39. doi: 10.1016/j.cell.2014.09.040. PMID: 25303535.
##co-first author

Differentiated human stem cells resemble fetal, not adult, β cells. Hrvatin S, O`Donnell CW, Deng F, Millman JR, Pagliuca FW, DiIorio P, Rezania A, Gifford DK, Melton DA. Proc Natl Acad Sci U S A. 2014 Feb 25;111(8):3038-43. doi:10.1073/pnas.1400709111. Epub 2014 Feb 10. PMID: 24516164.

Accurate control of oxygen level in cells during culture on silicone rubber membranes with application to stem cell differentiation. ##Powers DE, ##Millman JR, Bonner-Weir S, Rappel MJ, Colton CK. Biotechnol Prog. 2010 May-Jun;26(3):805-18. doi: 10.1002/btpr.359. PMID: 20039374.
##co-first author

The effects of low oxygen on self-renewal and differentiation of embryonic stem cells. Millman JR, Tan JH, Colton CK. Curr Opin Organ Transplant. 2009 Dec;14(6):694-700. doi: 10.1097/MOT.0b013e3283329d53. PMID: 19779343.

Engineering microenvironments for embryonic stem cell differentiation to cardiomyocytes. ##Horton RE, ##Millman JR, Colton CK, Auguste DT. Regen Med. 2009 Sep;4(5):721-32. doi: 10.2217/rme.09.48. PMID: 19761397.
##co-first author

Effects of oxygen on mouse embryonic stem cell growth, phenotype retention, and cellular energetics. Powers DE, Millman JR, Huang RB, Colton CK. Biotechnol Bioeng. 2008 Oct 1;101(2):241-54. doi: 10.1002/bit.21986. PMID: 18727033

Anisotropic particle synthesis in dielectrophoretically controlled microdroplet reactors. Millman JR, Bhatt KH, Prevo BG, Velev OD. Nat Mater. 2005 Jan;4(1):98-102. Epub 2004 Dec 19. PMID: 15608646.

Last Updated: 9/1/2016 9:23:31 AM

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