Tumorigenicity Studies for Human Pluripotent Stem Cell-Derived Products

Abstract

Human pluripotent stem cells (hPSCs), i.e. human embryonic stem cells and human induced pluripotent stem cells, are able to self-renew and differentiate into multiple cell types. Because of these abilities, numerous attempts have been made to utilize hPSCs in regenerative medicine/cell therapy. hPSCs are, however, also tumorigenic, that is, they can give rise to the progressive growth of tumor nodules in immunologically unresponsive animals. Therefore, assessing and managing the tumorigenicity of all final products is essential in order to prevent ectopic tissue formation, tumor development, and/or malignant transformation elicited by residual pluripotent stem cells after implantation. No detailed guideline for the tumorigenicity testing of hPSC-derived products has yet been issued for regenerative medicine/cell therapy, despite the urgent necessity. Here, we describe the current situations and issues related to the tumorigenicity testing of hPSC-derived products and we review the advantages and disadvantages of several types of tumorigenicity-associated tests. We also refer to important considerations in the execution and design of specific studies to monitor the tumorigenicity of hPSC-derived products.

Inhibition of stearoyl-coA desaturase selectively eliminates tumorigenic Nanog-positive cells: Improving the safety of iPS cell transplantation to myocardium

“…Therefore, elimination of residual pluripotent stem cells appears to be essential in order to prevent ectopic tissue formation, tumor development, and/or malignant transformation after implantation. 38 To achieve tumor-free ES-and iPS-derived CM transplantation, many labs are focused on enriching and/or purifying CM from stem cells 9 using genetic and non-genetic approaches. (1) Genetic approaches (which typically involve expression of selective proteins under the control of a cardiomyocyte-specific promoter, such as α-MHC, MLC-2v) yield CM that can reach about 99% purity.…”

Iron Administration before Stem Cell Harvest Enables MR Imaging Tracking after Transplantation

“…This approach requires multiple ex vivo manipulations of stem cells between their harvest and transplantation. Clinical translation of ex vivo-labeling procedures is complicated from a regulatory point of view, as these manipulations greatly enhance the risk of cell sample contamination (24), alterations in stem cell biology, or in vivo side effects from added transfection agents (25)(26)(27) (28). In addition, some ultrasmall superparamagnetic iron oxide-transfection agent combinations have induced cytotoxic effects (29)(30)(31)(32) or altered the stem cell biology (33).…”

Induced pluripotent stem cell-derived vascular smooth muscle cells: methods and application

“…So far no clinical trials have been performed using these cells due to a concern for potential tumorigenicity abilities of these cells [72–74]. There are very few preclinical studies that have been reported so far using iPSC-SMCs.…”