iPSC Technology Grows Even More Powerful and Disruptive

Since the discovery and development of induced pluripotent stem cell (iPSC or iPS cell) technology a decade ago, significant progress has been made within stem cell biology and regenerative medicine. In recent years, iPSCs have been used extensively in disease modeling, drug discovery, and cell therapy applications. Importantly, new pathological mechanisms have been identified and explained, new drugs identified by iPSC screens are in the pipeline, and clinical trials employing human iPSC-derived cell types have been initiated.

Furthermore, the combination of human iPSC technology with gene editing and three-dimensional organoids has made iPSC-based programs even more powerful and disruptive. Understandably, human iPSC technology offers great promise for human disease modeling, drug discovery, and cellular therapeutics, and this potential is only beginning to be ascertained. According to BioInformant’s estimates, the global iPSC industry is currently growing at a CAGR of 8.5%. (To view present market size metrics with future projections through 2030, please click here.)

Traditionally, animals have been used for disease modeling. However, species differences can prevent the recapitulation of full human disease phenotypes in specific animals, such as mice. This is due to basic species differences between mouse cells and human cells. This has necessitated the establishment of human disease modeling platforms to complement the various animal studies. Today, it is relatively easy to develop iPSCs from a patient’s fibroblasts or blood cells and use them to model various types of genetic diseases.

As these iPSCs become collected from patients, they are promoting the field of personalized disease modeling. Gene editing tools, such as zinc-finger nuclease (ZFN), transcription activator-like effector nucleases (TALENs), and CRISPR/Cas9 are also being used to edit and modify genes. Currently, diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), schizophrenia, and amyotrophic lateral sclerosis (ALS) have all been studied using iPSCs.

To date, iPSC-based drug screening has been used to assess more than 1,000 compounds and clinical candidates. Typically, it takes a great deal of time to differentiate iPSCs into disease-relevant cell types. Thus, researchers have also developed the direct conversion method to reprogram one somatic cell (e.g. skin fibroblast) into another somatic cell (e.g. myocardial cells, liver cells, or neural cells) without passing through the iPSC state. However, this area of direct cell programming is in its early stage and only a few companies, such as Fortuna Fix and Mogrify, are pursuing this type of technology.

During late-stage clinical studies, unexpected adverse effects of new drug candidates can cause hefty financial losses to a drug developer. Thus, toxicity screening using iPSC-derived cell types can help in the selection of potential drug candidates, as well as ensure that these candidates are less likely to fail due to toxicity in late-stage clinical trials. Cardiac and liver toxicities are the two most common adverse effects encountered during clinical trials.

For this reason, multi-electrode arrays (MEA) assays using iPSC-derived cardiomyocytes may provide a cost-effective alternative for preclinical in vitro testing of pro-arrhythmic risk. Similarly, iPSC-derived hepatic cell lines and functional 3D liver organ buds can be used to study hepatotoxicity. Also in use are iPSC-derived neuronal cells, mesenchymal stem cells (MSCs), and vascular endothelial cells.

The use of iPSC-derived cell types as cellular therapeutics has also attracted substantial interest. The earliest clinical study involving iPSCs within the cell therapy sector was one that treated macular degeneration using iPSC-derived retinal epithelial cells. This clinical trial used autologous (self-derived) iPSC-derived RPE cells for personalized cell therapy. Today, it costs approximately $800,000 to produce iPSC-derived autologous neuronal cells, cardiomyocytes, and RPE cells that are suitable for clinical use. Because allogeneic (donor-derived) treatments cost less per patient, the landmark Japanese trial using iPSC-derived RPE cells switched to using allogeneic RPE cells.

Of course, improvements in technologies, such as CRISPR/Cas9, 3D organoids, and microRNA switches, will further accelerate the already rapid pace of iPSC-based disease modeling and cell therapy development.

 Today, clinical studies using iPSC-derived cells for the following diseases are in advanced stages:

To learn more about this exciting market, view the “Global Induced Pluripotent Stem Cell (iPS Cell) Industry Report – Market Size, Trends, and Forecasts 2023.”