The Promise of Induced Pluripotent Stem Cells

Human embryonic stem cells (hESCs) hold great potential for cell replacement therapies, where cells are lost due to disease and/or injury. During the last decade, we have witnessed the development of the induced pluripotent stem cell (iPSC) technology, which revolutionized the stem cell field, as well as the regenerative medicine. Since the source of the reprogrammed cells (e.g., fibroblasts, keratinocytes, etc.) as part of the generation of iPSCs is readily accessible, this opened up an entirely new chapter in regenerative medicine by significantly reducing immune rejection problems after transplantation. Furthermore, by taking somatic cells directly from patients, we now have the ability to create disease models (also know as “disease in a dish”) for many conditions that were not possible before. As of today, numerous diseases have been modeled using iPSCs and many researchers are exploring the possibility of utilizing iPSC-derived cells for cell replacement therapy.

One of the pioneers of the iPSC work, Shinya Yamanaka, was awarded the Nobel Prize in Physiology or Medicine (together with John B. Gurdon) this year. Considering that Dr. Yamanaka’s first study related to iPSCs was published in 2006, it’s easy to appreciate the enormous impact that this technology has created as substantiated by the decision of the Nobel Prize committee. If we look back at the chronological events, the initial report from the Yamanaka group using mouse fibroblast and 4 transcription factors (i.e., Oct4, Sox2, Klf4 and c-Myc) to create iPSCs was published in 2006 (Takahashi and Yamanaka, 2006), followed by the demonstration in 2007 (Takahashi et al., 2007) that a similar approach was applicable for human fibroblasts, and by introducing a defined set of transcription factors, human iPSCs can be generated. On the same day Yamanaka published his human iPSC paper, Jamie Thomson’s group also demonstrated the generation of iPSCs from human cells using a different set of factors (Yu et al., 2007).

describe the imageEven though, iPSCs can be generated reproducibly, the efficiency of the reprograming remains low (i.e., around 1% using the original method). Furthermore, the initial generation of iPSCs utilized either retroviruses or lentiviruses, which both integrate into the host genome and might cause insertional mutagenesis, collectively creating a risk for translational applications. However, the beauty of the iPSC technology is its simplicity and reproducibility. Since 2007, iPSCs have been in the central focus of stem cell research and regenerative medicine, and researchers throughout the world have made a number of improvements to Yamanaka’s original protocol. Today, we have safer and more efficient methods for generation human iPSCs for disease modeling or cell replacement therapies, and by the look of how much has been achieved so far, the technology is only going to get better and more proficient. Considering that human embryonic stem cell derived approaches have been successfully used at the clinical level for cell replacement therapies, there is no doubt that iPSCs will eventually prove to be the ultimate source for regenerative medicine in the future.