JDRF Timeline: Stem Cell Therapies

in , ,

Douglas Melton Beta Cells

Stem cells—first isolated by scientists in 1998—have two unique characteristics, with unique translatable potential: (1) They can be made to replicate themselves again and again without changing their essential nature, and (2) they can develop into virtually any type of human tissue. Stem cells have the potential to lead to treatments for type 1 diabetes (T1D), but it has taken us more than 20 years to get to this point. Read on.

Hear more from Dr. Melton about his search for T1D cures in our Meet the Scientist Video.

1999JDRF testifies at one of the first congressional hearings on stem cell research.
1999JDRF forms first patient advocacy organization to support stem cell research.
2000JDRF funds a 10-year grant to Douglas Melton, Ph.D., for almost $1.4 million, to make beta cells from stem cells.
2000Investigators at the JDRF Center for Islet Transplantation—including Dr. Melton and Nissim Benvenisty, M.D., Ph.D.—demonstrate that growth factors could direct the development of human stem cells, setting the stage for the development of beta cells from stem cells in the laboratory.[1]
2001JDRF leads the creation of a coalition of patient and health advocacy organizations and research institutions to promote favorable stem cell research policies. JDRF is involved in congressional hearings, press conferences, and builds support for congressional sign-on letters to the Administration.
2001JDRF meets with President Bush and Vice President Cheney in the White House to discuss stem cell research. A few weeks later, President Bush, in his first national prime time address, announces federal policy on stem cell research.
2002JDRF creates $20 million Stem Cell Research Development Fund and launches focused stem cell funding efforts worldwide.
2003JDRF leads an effort, along with coalition partners, to promote dialogue on stem cell research with the public at large, on Capitol Hill, and in the Administration. A JDRF scientific white paper, “Why Federal Stem Cell Policy Must Be Expanded,” analyzes the state of stem cell research in the U.S. and articulates the case for expansion of the federal policy.
2003Dr. Melton announced the development of 17 new stem cell lines, and JDRF provides support for the distribution of them.
2004JDRF and coalition partners build support in Congress—206 Representatives and 58 Senators sign letters to Administration calling for a review and expansion of federal stem cell policy.
2006JDRF and coalition partners build support in Congress for expanded policy—legislation passes House and Senate but is vetoed.
October 2006Novocell develops a way to convert stem cells into insulin-producing cells, with partial funding from JDRF.[2] The cells do not secrete much insulin and don’t do so in response to glucose, but the research represents a vital first step in coaxing stem cells to become cells that sense blood sugar and ultimately produce insulin in response.
2007JDRF and coalition partners build support in Congress for expanded policy again—legislation passes House and Senate but is vetoed.
2009An Executive Order for which JDRF had advocated is signed by the President, significantly expanding the number of stem cell lines which can be utilized in federally-funded research.
2009The California Institute of Regenerative Medicine (CIRM), created in 2004 with leadership from JDRF advocacy, awards $20 million to the Novocell Disease Team.
November 2011JDRF supports ViaCyte (formerly Novocell, which resulted in a three-way merger with Novocell, CyThera, and BresaGen), which is developing an encapsulated beta cell replacement therapy that combines precursor beta cells made from stem cells that, over time, develop into mature pancreatic hormone-producing cells, including insulin-producing cells.
November 2011JDRF has its first educational symposium with FDA. They have taken place quarterly every year since.
March 2013JDRF launches the Encapsulation Consortium, including researchers with expertise in bioengineering, beta cell biology, pancreatic transplants, and materials science, who will work to develop and incorporate new engineering concepts and designs that will improve cell encapsulation.
September 2014ViaCyte starts its clinical trial of the first ever stem cell-derived encapsulated cell replacement therapy, VC-01™.[3],[4] The trial will enroll approximately 60 people at multiple clinical sites.
September / October 2014Significant progress in made in making beta cells in the lab: Two JDRF-funded investigators—Dr. Melton and Timothy Kieffer, Ph.D.—develop a method for converting stem cells into insulin-producing beta cells.[5],[6]
2015Dr. Melton founded Semma Therapeutics in 2015 to develop stem cell-derived beta cells into curative therapies for T1D.
2017In early 2017, the JDRF T1D Fund made a catalytic investment in Semma, to bridge the company to its next large venture round, which took place at the end of that year.
September 2019Vertex Pharmaceuticals acquires Semma Therapeutics for nearly $1 billion.[7]
October 2019ViaCyte has shown—for the first time ever—that its VC-01™ therapy helps people with T1D produce insulin again.[8] Preliminary data show that when pancreatic precursor cells, called “PEC-01 cells,” are implanted under the skin and properly engrafted, they are capable of producing circulating C-peptide, a biomarker for insulin, in people with T1D.
October 2020JDRF-funded researchers partner with the Advanced Regenerative Manufacturing Institute (ARMI) to translate the manual process to create stem cell-derived beta cells into a robust, reproducible, and automated procedure, for the eventual development as a replacement therapy for people with T1D.[9],[10],[11]
March 2021Vertex launches the clinical trial of VX-880, which uses stem cell-derived beta cells (pioneered by Dr. Melton) to try to restore the body’s ability to produce insulin, in combination with immunosuppressive therapy to protect the cells from rejection, for people with T1D with severe low blood-sugar (called hypoglycemia) events and those who struggle to perceive the onset of hypoglycemia.[12]  

The FDA granted Fast Track designation to Vertex—the first cell therapy in diabetes to receive this distinction.
October 2021  Vertex announces promising data from its phase I/II clinical trial, that the first person to receive VX-880, the stem cell derived therapy for use in people living with T1D, needs 91% less insulin 90 days after receiving an infusion of these fully differentiated cells at just half the target dose, and other clinically meaningful benefits.
November 2021A new first for ViaCyte and CRISPR Therapeutics: Gene-editing for T1D. By the end of the year, they will start a clinical trial of VCTX210, a gene-edited stem cell replacement therapy for this disease. Combining ViaCyte’s leading stem cell capabilities, which were developed with significant support from JDRF, with CRISPR Therapeutics’ pre-eminent gene-editing platform, has significant potential in the development of a cell replacement therapy that does not require immune suppression, advancing ViaCyte’s mission of providing a cure for diabetes and JDRF’s vision of a world without T1D.
JDRF Leadership: JDRF has been a long-time and significant supporter of ViaCyte, supporting the company through research funding, as well as advocating for government funding for the California Institute of Regenerative Medicine, which also supported ViaCyte. Our funding 15 years ago (when ViaCyte was called Novocell) underwrote development of the proprietary line of precursor stem cells used in their treatment. JDRF also funded the preclinical and clinical studies of ViaCyte’s PEC-01™ therapies, which are designed to mature into islet tissue in humans, including glucose-responsive insulin-secreting beta cells. This includes the first ever clinical trial to test a stem cell-derived cell replacement therapy for T1D, in 2014.
July 2022Vertex Pharmaceuticals announces that they have acquired ViaCyte for $320 million in cash to help speed up the development of VX-880, Vertex’s stem cell-derived therapy for people with T1D. Vertex and ViaCyte have been working independently to develop cell replacement therapies for people with T1D. This merger brings two of the biggest companies pursuing this technology for diabetes together, and will allow them to combine their resources, technologies, intellectual property, and more.

[1] Schuldiner M, Yanuka O, Itskovitz-Eldor J, Melton DA, Benvenisty N. Effects of eight growth factors on the differentiation of cells derived from human embryonic stem cells. Proc Natl Acad Sci U S A. 2000; 97 (21): 11307-11312. https://doi.org/10.1073/pnas.97.21.11307

[2] D’Amour KA, Bang AG, Eliazer S, Kelly OG, Agulnick AD, Smart NG, Moorman MA, Kroon E, Carpenter MK, Baetge EE. Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat Biotechnol. 2006 Nov; 24 (11): 1392-401. https://doi.org/10.1038/nbt1259

[3] https://www.jdrf.org/blog/2014/08/19/jdrf-partner-viacyte-to-immediately-initiate-type-1-diabetes-clinical-trial

[4] https://clinicaltrials.gov/ct2/show/results/NCT02239354

[5] Rezania A, Bruin JE, Arora P, Rubin A, Batushansky I, Asadi A, O’Dwyer S, Quiskamp N, Mojibian M, Albrecht T, Yang YH, Johnson JD, Kieffer TJ. Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells. Nat Biotechnol. 2014 Nov; 32 (11): 1121-33. https://doi.org/10.1038/nbt.3033

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

[7] https://www.jdrf.org/blog/2019/09/04/semma-therapeutics-backed-jdrf-t1d-fund-acquired-major-biopharma-company/

[8] https://www.jdrf.org/blog/2019/10/03/viacyte-announces-insulin-production-people-t1d/

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

[10] Hogrebe NJ, Augsornworawat P, Maxwell KG, Velazco-Cruz L, Millman JR. Targeting the cytoskeleton to direct pancreatic differentiation of human pluripotent stem cells. Nat Biotechnol. 2020; 38 (4): 460-470. https://doi.org/10.1038/s41587-020-0430-6

[11] Maxwell KG, Augsornworawat P, Velazco-Cruz L, Kim MH, Asada R, Hogrebe NJ, Morikawa S, Urano F, Millman JR. Gene-edited human stem cell-derived β cells from a patient with monogenic diabetes reverse preexisting diabetes in mice. Sci Transl Med. 2020 Apr 22; 12 (540): eaax9106. https://doi.org/10.1126/scitranslmed.aax9106

[12] https://www.jdrf.org/blog/2021/02/01/vertex-new-horizon-curing-type-1-diabetes/