Special cells, special considerations: the challenges of bringing embryonic stem cells from the laboratory to the clinic

Abstract

Human embryonic stem (ES) cells are an attractive tool for cell-based therapies because of their limitless capacity for proliferation and their ability to differentiate into all cell types of the body. However, these features introduce certain unique risks that must be considered in developing transplantation strategies for clinical use. We outline these risks and examine current approaches to address them, both before and after transplantation.

Figure 1

Noninvasive imaging. MRI of (a,b) Feridex-labeled and (c,d) LRP-transfected cells. 5 × 10⁵ Feridex-labeled cells were transplanted into one side of NOD-SCID mouse brain, represented by a hypo-intense area (a, arrow). A 3D reconstruction of the raw data along with color segmentation and surface rendering allows overall visualization of the distribution of cells (b, arrow). 5 × 10⁴ LRP-transfected rat glioma cells were transplanted in the left hemisphere of NOD-SCID mouse brain; cells transfected with empty vector were injected contralaterally. Shown are the anatomical image (c) and the CEST signal intensity–difference map overlaid on the anatomical image (d), distinguishing LRP-expressing and control xenografts. (Panels a and b courtesy of Candace Kerr and Piotr Walczak; panels c and d reprinted from ref. with permission.)

Figure 2

Noninvasive bioluminescent imaging of ES-cell survival, proliferation, and teratoma formation. 1 × 10⁶ ES-DF (double-fusion reporter, containing luciferase and GFP, but lacking truncated thymidine kinase (ttk)) cells were injected subcutaneously into the left shoulder and 1 × 10⁶ ES-TF (triple-fusion reporter, containing luciferase and GFP as well as ttk) cells into the right shoulder of mice. Serial imaging over 2 weeks showed progressive increase in imaging signals (top row). To prevent teratoma formation, ganciclovir treatment was started from week 2 to week 5. At week 5, ES-TF cells carrying the HSV-ttk reporter-suicide gene showed background bioluminescent signal levels, whereas ES-DF cells lacking HSV-ttk showed dramatic increases in signal activity. (Reprinted from ref. with permission.)