Results: 3

1.
Fig. 3

Fig. 3. Time course of tumor infiltration by neuralized embryonic stem cells on an organotypic brain slice. From: Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas.

These stereoscopic epifluorescent images show the progression of tumor mass infiltration by nESCs over the course of a several weeks in an organotypic brain slice culture. GFP-expressing nESCs and RFP-expressing human glioma cells were introduced on the surface of an organotypic rat brain slice as described in Fig. 2. (A–C) Starting at 2 weeks post-implantation, nESCs are found at the tumor mass. At 3 weeks (D–F) and 4 weeks (G–I) post-implantation, the tumor mass becomes infiltrated progressively by nESCs. At 6 weeks (J–L), the tumor mass becomes encapsulated completely by the stem cells, suggesting contiguity between nESCs and glioma cells. Scale bar = 1 mm; Scale bar applies to all panels.

Prakash Rath, et al. Curr Stem Cell Res Ther. ;4(1):44-49.
2.
Fig. 2

Fig. 2. GFP-expressing neuralized mouse embryonic stem cells (nESCs) co-localize with RFP-expressing human tumor cells in an organotypic brain slice. From: Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas.

Stereoscopic epifluorescent images show tumor mass infiltration by nESCs. GFP-expressing nESCs and RFP-expressing human glioma cells were introduced on the surface of the organotypic rat brain slice. The living brain section was obtained from a 300-micron thick coronal slice just anterior to bregma obtained from a fresh rat brain embedded in agarose and cut with a vibratome. Initially, 10 μl (~8,000 cells/μl) of both cell types were simultaneously implanted at separate locations on the surface of a one-week old slice. Aliquots of the two cell types were applied approximately 10 mm from each other across the width of the organotypic slice. Images shown here were taken one week after implantation of the nESCs and glioma cells. (A–D) Stereomicroscopic epifluoresent images show that stem cells placed distant from the tumor cells co-localized with tumor cells and were not detectable in other regions of the brain slice. Scale bars = 1 mm; Scale bar in C applies to A–C.

Prakash Rath, et al. Curr Stem Cell Res Ther. ;4(1):44-49.
3.
Fig. 1

Fig. 1. Suicide gene therapy and the bystander effect. From: Stem Cells as Vectors to Deliver HSV/tk Gene Therapy for Malignant Gliomas.

(a) Transduced stem cells (green) that express constitutively Herpes Simplex Virus thymidine kinase (HSV-TK) migrate to the vicinity of GBM cells (red). (b) Upon systemic administration of the non-toxic, antiviral drug ganciclovir (GCV), GCV is mono-phosphorylated (GCV-P) by the viral TK enzyme in the stem cells. (c) Gap junctions present between cells facilitate the passive transport of GCV-P to adjacent non-transduced target GBM cells. (d) GCV-P may also be transported to GBM cells via a gap junction-independent pathway. (e) Endogenous mammalian kinases within the GBM cells further phosphorylate GCV-P to its toxic product (GCV-PPP). (f, g) GCV-PPP acts as a purine analog incorporating itself into nascent DNA where it terminates replication, resulting in apoptosis of rapidly dividing cells. The death of non-transduced cells due to the transfer of an oncolytic agent is referred to as the bystander effect and in conjunction with concurrent suicide of transduced cells by the same mechanism involving GCV-PPP, is collectively known as suicide gene therapy. Figure adapted from Hurwitz et al. 2003 [16].

Prakash Rath, et al. Curr Stem Cell Res Ther. ;4(1):44-49.

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