Induced pluripotent stem cells: opportunities and challenges

Abstract

Somatic cells have been reprogrammed into pluripotent stem cells by introducing a combination of several transcription factors, such as Oct3/4, Sox2, Klf4 and c-Myc. Induced pluripotent stem (iPS) cells from a patient's somatic cells could be a useful source for drug discovery and cell transplantation therapies. However, most human iPS cells are made by viral vectors, such as retrovirus and lentivirus, which integrate the reprogramming factors into the host genomes and may increase the risk of tumour formation. Several non-integration methods have been reported to overcome the safety concern associated with the generation of iPS cells, such as transient expression of the reprogramming factors using adenovirus vectors or plasmids, and direct delivery of reprogramming proteins. Although these transient expression methods could avoid genomic alteration of iPS cells, they are inefficient. Several studies of gene expression, epigenetic modification and differentiation revealed the insufficient reprogramming of iPS cells, thus suggesting the need for improvement of the reprogramming procedure not only in quantity but also in quality. This report will summarize the current knowledge of iPS generation and discuss future reprogramming methods for medical application.

Cancer stem cell definitions and terminology: the devil is in the details

“…This is an intriguing idea particularly in light of the growing number of major regulators of the epigenome that are commonly altered in malignant populations 51 . In addition, we now know that only a handful of oncogenes can turn almost any mammalian cell into an embryonic stem cell (ESC)-like cell, which often retains tumorigenic potential even after participating in normal embryogenesis 52 . However, whether reprogramming has an important role in the generation and evolution of human tumours is unknown and will also be very challenging to investigate, as functional assays attribute a CSC state exclusively to cells that display a sustained tumour-generating ability (in vivo).…”

Reprogramming and Carcinogenesis—Parallels and Distinctions

“…Transfected cells tend to contain viral remains following transduction, that requires additional techniques for removal (Okita and Yamanaka, 2011).…”

The evolving biology of cell reprogramming

“…In some cases, these are able to replace one of the four factors identified by Yamanaka (often referred to as the Yamanaka factors), while in others they complement the standard protocol. This topic is reviewed by Okita & Yamanaka [13] in this issue.…”

“…Empirical attempts to overcome these limitations are described in table 1 and are further discussed by Okita & Yamanaka [13]. The PiggyBac vector has been used to introduce all four proteins in a single transcript [19].…”