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StemoniX was conceived by co-founder and current CEO Ping Yeh. Ping, a survivor of non-Hodgkin’s Lymphoma, was inspired to find new ways to test and identify new medicines after being told that there was a good chance his chemotherapy regimen might permanently damage his heart. Ping was one of the lucky ones – and was inspired to make everyone a lucky one.

A (very) brief history of iPSCs

Sixty years ago, two Canadian scientists, Ernest McCulloch and James Till (along with graduate student Andy Becker and senior scientist Lou Siminovitch), identified stem cells in mice and described the two main hallmarks of stem cells: self-renewal (making more stem cells) and differentiation (becoming more specialized).[1] While these multipotent stem cells have the ability to differentiate into related cell types of the organism, they are difficult to identify and to obtain.

In the 1980s and 1990s, embryonic stem cells (ESCs) were identified in mice and humans, respectively, but with this scientific advance came an ethical dilemma; harvesting ESCs means destroying 3-5 day old embryos. In 2006, Shinya Yamanaka, a scientist at both Kyoto University and UCSF, built upon the work of Sir John Gordon, a scientist at the University of Cambridge, to identify the factors that could make an adult skin cell revert to their embryonic state - pluripotent stem cells [2] – an achievement for which the two men were awarded the Nobel Prize in Physiology or Medicine in 2012. With the right prompting, induced pluripotent stem cells (iPSCs) can differentiate into any cell type, and in the years following Yamanaka’s group’s breakthrough, scientists have worked to coax iPSCs into organ-specific cell types.

Initially, iPSC-derived tissue cells were cultured the same way that immortalized cells were – one cell type on a flat surface. Over time, however, scientists learned that growing complex cultures in 3D created structures, known generally as organoids, better reflected the function of the cells in the native tissue.

If I only had a brain…

The advent of human iPSC-derived neural cultures [3] gave scientists access to unlimited quantities of human neural tissue that then enabled a greater understanding of neural development, function, and neurodegeneration in both healthy and pathological conditions. This has led to a subsequent resurgence in drug discovery efforts aimed at curing previously intractable neurological diseases. Growing these cells as organoids allows for more accurate drug testing and toxicity studies and better disease modeling – experiments that could not be done previously because cells and models were lacking.

iPSC-derived neural cultures are relatively easy to obtain and create from a variety of genetic donors, which provides a broader basis for drug discovery for both developmental and adult diseases. Because these cells can be derived from anyone, they can be used to study treatments for genetic diseases, even when the underlying genetic condition is not known. Similarly, iPSCs used for drug discovery can be genetically modified using techniques such as CRISPER/Cas 9 editing, which allows custom tailoring of genetic disease models.

What makes StemoniX microBrain 3D platform unique?

StemoniX has moved the technology for drug discovery forward introducing high-throughput, iPSC-derived screening platforms. microBrain 3D, our iPSC-derived neural tissue platform, is different from other organoid platforms in that each well contains a single neural spheroid comprised of co-matured cortical neurons and astrocytes. The uniform, highly functional tissues coupled with consistency, ease of use, and speed of high-throughput make the microBrain 3D platform perfect for testing new compounds and new compound combinations.

Terms to know:

Multipotent Stem Cell: Cells can self-renew by dividing and can develop into multiple types of specialized cell types present in a given tissue or organ. Example: Most adult stem cells.

Pluripotent Stem Cell: Cells that can self-renew by dividing and can differentiate into all cell types of the adult body. Example: Embryonic stem cells and induced pluripotent stem cells.

Induced Pluripotent Stem Cell: Terminally differentiated adult cell that has reprogrammed into a pluripotent stem cell through introduction of the four Yamanaka factors.

1. Till, McCulloch, and Siminovitch. A stochastic model of stem cell proliferation, based on the growth of spleen colony-forming cells. Proc Natl Acad Sci U.S.A. 51(1): 29–36 (1964).

2. Takahashi and Yamanaka. Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell 126(4), 663-676 (2006).

3. Cohen, D., Melton, D. Turning straw into gold: directing cell fate for regenerative medicine. Nat Rev Genet 12, 243–252 (2011). https://doi.org/10.1038/nrg2938.

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