Figure 4.

Histology of cross-sections from an explanted dose-finding unit at approximately 11 months from “Subject E-002”

Several panels illustrate the histological features routinely observed in the cellular regions of VC-02 grafts. Shown are “nearly adjacent” sections. Gray strips seen at the top and bottom of each image are the delivery device membranes.

(A) H&E staining reveals densely packed cells reminiscent of human endocrine islet morphologies, albeit without the macro-anatomical “islet” nature.

(B) Nearly all graft-derived cells are endodermal in nature as demonstrated by nuclear staining to the transcription factors FOXA2 and CDX2. The open structure lined with endodermal cells, exemplified in the lower left of each image, is not a prominent feature but observed occasionally in the cellular regions of the grafts.

(C) A subset of graft-derived cells coincident with insulin-expressing cells show nuclear immunoreactivity for NKX6-1, a transcription factor specific to β cells in mature human islets.

(D) The cellular regions are well vascularized with microcapillary structure, demonstrated with the endothelial cell marker CD34 (magenta). CD3 staining (brown) marks T cells, not abundant but observed occasionally outside the device lumen, but rarely inside the lumen among graft-derived cells.

(E) Many cells show glucagon (GCG) immunoreactivity.

(F) Many cells show insulin (INS) immunoreactivity in regions coincident with NKX6-1 expression. Scale bars, 250 μm. Counterstain is hematoxylin.