Our iPSC Differentiation Technology

Fast and easy iPSC differentiation enables more effective ways to model human biology and disease, opening the door to a wealth of applications.

The Promise of iPSCs

Human induced pluripotent stem cells (iPSCs) have been expected to drive the stem cell revolution by giving researchers an almost alchemical ability to transform one type of cell into virtually any other type of cell. Instead of hunting for rare stem cells, researchers could create iPSCs and then differentiate the iPSCs into neurons, skeletal muscle cells, hepatocytes, and so on, enabling studies on impossible-to-obtain human cells, creating an unlimited supply of genetically-identical human cells for tightly-controlled bioproduction and high-throughput screening, and developing novel cell-based therapeutics.

In addition, by providing a better model for human biology and disease than primary cells derived from animal models, human iPSCs can reduce our dependence on the use of animals for research.

Bar graph depicting variations in published differentiation time scales for iPSC differentiation

The Challenge of iPSCs

However, iPSCs have not had as significant an impact on our understanding of human biology or the advancement of human health as many scientists might have hoped for, as the iPSC differentiation process has proven to be technically challenging, labor-intensive, and time-consuming. Few labs can consistently differentiate a variety of iPSC lines into healthy, functional, and pure populations of target cells.

The Technology that Brings the Full Promise of iPSCs to Every Lab

Elixirgen Scientific has developed an iPSC differentiation technology that makes it possible for any lab to quickly and easily generate iPSC-derived cells in as little as 1-2 weeks. Our transcription factor-based approach leaves the genome untouched, maintaining the physiological relevance of the cells, and is consistently successful for the reliable generation of target tissue. Available as differentiation kits that deliver the transcription factors through equally efficient mRNA or non-integrating Sendai virus formats, Elixirgen Scientific’s iPSC differentiation technology puts all the advantages of iPSC-derived cells into the hands of every lab.

Transcription-factor Based iPSC Differentiation

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

The approach is conceptually very simple—introduce a specific set of transcription factors to iPSCs/ESCs at the appropriate times and in the appropriate media to promote differentiation into the desired cell type. The power behind Elixirgen Scientific’s approach is the hard work spent identifying the right transcription factors, the right time, and the right media.

The Scientific History of Our iPSC Differentiation Technology

While at the National Institute of Aging, Dr. Ko used mouse ES cells to establish and demonstrate the principles of the transcription factor-based iPSC differentiation approach that Elixirgen Scientific’s scientists use today. His lab also generated a large number of mouse ES cell clones and gene expression profiles that are still in use today and available to the research community through the Coriell Cell Repository.

The research at Keio University 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

Making targeted cell-based therapies a more widespread option will require research into ways to reduce the costs of generating custom, autologous cells. Elixirgen Scientific’s cells and kits accelerate these studies with our rapid, consistent, and efficient 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