The Science Behind Our Technology

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The Problem Facing Researchers

Human induced pluripotent stem cells (iPSCs) are powerful tools for studying specialized cell types, for disease modeling, and for developing therapeutic strategies.

They are an excellent alternative to other popular model systems, such as immortalized human cells and primary neurons of rodent origin, because human iPSCs carry the normal karyotype and offer an unlimited supply of physiologically relevant materials that help reduce the variability across experiments.

However, one drawback of human iPSCs is that manipulation of their differentiation into the desired cell type is a very time and labor intensive process.

Our Solution

To overcome this research bottleneck, we provide a variety of products and services to greatly reduce the time and effort required for stem cell differentiation so researchers can get their data sooner and free up time to focus on more important tasks.

Our technology is based on the efficient introduction of key transcription factors into human pluripotent cells via synthetic mRNAs or Sendai virus RNA vectors to induce differentiation.

Transcription-factor Based iPSC Differentiation

Our technology is based on research spanning over 20 years in the laboratory of Minoru Ko, M.D., Ph.D at the National Institute of Aging (1998-2011) and Keio University School of Medicine (2012-present).

The project at the National Institute of Aging established and demonstrated the principles we use today using mouse ES cells and also generated a large number of mouse ES cell clones and gene expression profiles that are available to the research community through the Coriell Cell Repository.

The research at Keio extended this work further into the more biologically relevant human ES and iPS cells. These technologies have been exclusively licensed from Keio University to Elixirgen Scientific.

Applications

iPSC-derived cells are an incredibly enabling technology with applications that span a range of life science segments, including 3D bioprinting, toxicity and drug screening, precision medicine approaches (personalized drugs), tissue chips, disease modeling, transplantation therapy, and more.

3D Bioprinting

A rapidly growing area in the field of bioengineering, 3D bioprinting holds out the hope of replacing the need for organ transplants with the ability to “print” cells into complex, multicellular three-dimensional tissues. With a faster, easier workflow than any other technology on the market, Elixirgen Scientific’s Quick-Tissue™ cells and kits are the ideal reagents for 3D bioprinting. Our technology enables differentiation of stem cells already printed onto the top of the scaffold, one of the most widely used techniques currently used in 3D bioprinting.

High-throughput Compound Screening

With the ability to produce virtually unlimited amounts of identical cells, Elixirgen Scientific’s iPSC differentiation technology enables more consistent, reproducible, and physiologically relevant high-throughput screening (HTS) than immortalized cell lines, and are more affordable and scalable than primary cells. In addition, the streamlined workflow is compatible with automated platforms, making the Quick-Tissue™ Series a perfect fit for efficient HTS operations.

Precision Medicine, Cell-based Therapies

One of the future goals in widely discussed “Precision Medicine” is to select the most suitable drugs for individual patients (“personalized or tailored medicine”).

Our kits help to achieve these dreams by providing rapid, efficient, and reproducible differentiation of patient-specific iPS cells into desired cell types.

Tissue Chips

“Tissue Chips” and “organs-on-chips” are technologies being developed to provide a more humane and physiologically relevant method for testing the safety and efficacy of drug candidates than animal studies. Elixirgen Scientific’s Quick-Tissue™ Series kits are an excellent choice for this application thanks to the fast and streamlined differentiation workflow that can be performed directly on the chip.

Research Models

Researchers have traditionally used non-human cells, such as mouse cells, for basic, translational, and applied research because of the lack of suitable human cell lines and/or the impossibility of obtaining primary cells from humans. But the advent of human ES cells and iPS cells has changed this situation, as these pluripotent cells differentiate into essentially any type of cell in the human body. With the Quick-Tissue™ Series kits, human iPSC-derived cells can be generated quickly and easily in any lab, opening the door to more physiologically-relevant models for human biology and disease.

Transplantation

One of the key paradigms of regenerative medicine is to differentiate human ES and iPS cells into desired cell types and transplant them into patients in need of these cells/tissue/organs. Examples include skeletal muscles for Muscular Dystrophy, dopaminergic neurons for Parkinson’s disease, pancreatic beta-cells for Diabetes, cardiomyocytes for heart failures and myocardial infarction. The technology used in the Quick-Tissue™ Series enables the development of these approaches through rapid, reliable, and consistent differentiation of desired cell types from human ES and iPS cells.

Publications

Nakatake Y, Ko SBH, Sharov AA, Wakabayashi S, Murakami M, Sakota M, Chikazawa N, Ookura C, Sato S, Ito N, Ishikawa-Hirayama M, Mak SS, Jakt LM, Ueno T, Hiratsuka K, Matsushita M, Goparaju SK, Akiyama T, Ishiguro KI, Oda M, Gouda N, Umezawa A, Akutsu H, Nishimura K, Matoba R, Ohara O, Ko MSH.

Generation and Profiling of 2,135 Human ESC Lines for the Systematic Analyses of Cell States Perturbed by Inducing Single Transcription Factors. Cell Rep. 2020 May 19;31(7). PubMed

Akiyama T, Sato S, Chikazawa-Nohtomi N, Soma A, Kimura H, Wakabayashi S, Ko SBH, Ko MSH.

Efficient differentiation of human pluripotent stem cells into skeletal muscle cells by combining RNA-based MYOD1-expression and POU5F1-silencing. Sci Rep. 2018 Jan 19;8(1):1189. PubMed

Matsushita M, Nakatake Y, Arai I, Ibata K, Kohda K, Goparaju SK, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Kanai T, Yuzaki M, Ko MSH.

Neural differentiation of human embryonic stem cells induced by the transgene-mediated overexpression of single transcription factors. Biochem Biophys Res Commun. 2017 Aug 19;490(2):296-301. PubMed

Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SBH, Ko MSH.

Epigenetic Manipulation Facilitates the Generation of Skeletal Muscle Cells from Pluripotent Stem Cells. Stem Cells Int. 2017;2017:7215010. PubMed

Goparaju SK, Kohda K, Ibata K, Soma A, Nakatake Y, Akiyama T, Wakabayashi S, Matsushita M, Sakota M, Kimura H, Yuzaki M, Ko SB, Ko MS.

Rapid differentiation of human pluripotent stem cells into functional neurons by mRNAs encoding transcription factors. Sci Rep. 2017 Feb 13;7:42367. PubMed

Hirayama M, Ko SB, Kawakita T, Akiyama T, Goparaju SK, Soma A, Nakatake Y, Sakota M, Chikazawa-Nohtomi N, Shimmura S, Tsubota K, Ko MS.

Identification of transcription factors that promote the differentiation of human pluripotent stem cells into lacrimal gland epithelium-like cells. npj Aging and Mechanisms of Disease 2017; 3: 1. PubMed

Akiyama T, Wakabayashi S, Soma A, Sato S, Nakatake Y, Oda M, Murakami M, Sakota M, Chikazawa-Nohtomi N, Ko SB, Ko MS.

Transient ectopic expression of the histone demethylase JMJD3 accelerates the differentiation of human pluripotent stem cells. Development. 2016 Oct 15;143(20):3674-3685. PubMed

Teratani-Ota Y, Yamamizu K, Piao Y, Sharova L, Amano M, Yu H, Schlessinger D, Ko MS, Sharov AA.

Induction of specific neuron types by overexpression of single transcription factors. In Vitro Cell Dev Biol Anim. 2016 Oct;52(9):961-973. PubMed

Yamamizu K, Sharov AA, Piao Y, Amano M, Yu H, Nishiyama A, Dudekula DB, Schlessinger D, Ko MS. (2016).

Generation and gene expression profiling of 48 transcription-factor-inducible mouse embryonic stem cell lines. Sci Rep. 2016 May 6;6:25667. PubMed

Yamamizu K, Piao Y, Sharov AA, Zsiros V, Yu H, Nakazawa K, Schlessinger D, Ko MS.

Identification of transcription factors for lineage-specific ESC differentiation. Stem Cell Reports. 2013 Nov 27;1(6):545-59. PubMed

Nishiyama A, Sharov AA, Piao Y, Amano M, Amano T, Hoang HG, Binder BY, Tapnio R, Bassey U, Malinou JN, Correa-Cerro LS, Yu H, Xin L, Meyers E, Zalzman M, Nakatake Y, Stagg C, Sharova L, Qian Y, Dudekula D, Sheer S, Cadet JS, Hirata T, Yang HT, Goldberg I, Evans MK, Longo DL, Schlessinger D, Ko MS. (2013).

Systematic repression of transcription factors reveals limited patterns of gene expression changes in ES cells. Sci Rep. 2013;3:1390. PubMed

Correa-Cerro LS, Piao Y, Sharov AA, Nishiyama A, Cadet JS, Yu H, Sharova LV, Xin L, Hoang HG, Thomas M, Qian Y, Dudekula DB, Meyers E, Binder BY, Mowrer G, Bassey U, Longo DL, Schlessinger D, Ko MS. (2011).

Generation of mouse ES cell lines engineered for the forced induction of transcription factors. Sci Rep 2011; 1: 167. PubMed

Nishiyama A, Xin L, Sharov AA, Thomas M, Mowrer G, Meyers E, Piao Y, Mehta S, Yee S, Nakatake Y, Stagg C, Sharova L, Correa-Cerro LS, Bassey U, Hoang H, Kim E, Tapnio R, Qian Y, Dudekula D, Zalzman M, Li M, Falco G, Yang HT, Lee SL, Monti M, Stanghellini I, Islam MN, Nagaraja R, Goldberg I, Wang W, Longo DL, Schlessinger D, Ko MS. (2009).

Uncovering early response of gene regulatory networks in ESCs by systematic induction of transcription factors. Cell Stem Cell. 2009 Oct 2;5(4):420-33. PubMed