3-D Imaging Reveals Participation of Donor Islet Schwann Cells and Pericytes in Islet Transplantation and Graft Neurovascular Regeneration

Abstract

The primary cells that participate in islet transplantation are the endocrine cells. However, in the islet microenvironment, the endocrine cells are closely associated with the neurovascular tissues consisting of the Schwann cells and pericytes, which form sheaths/barriers at the islet exterior and interior borders. The two cell types have shown their plasticity in islet injury, but their roles in transplantation remain unclear. In this research, we applied 3-dimensional neurovascular histology with cell tracing to reveal the participation of Schwann cells and pericytes in mouse islet transplantation. Longitudinal studies of the grafts under the kidney capsule identify that the donor Schwann cells and pericytes re-associate with the engrafted islets at the peri-graft and perivascular domains, respectively, indicating their adaptability in transplantation. Based on the morphological proximity and cellular reactivity, we propose that the new islet microenvironment should include the peri-graft Schwann cell sheath and perivascular pericytes as an integral part of the new tissue.

Pancreatic islet blood flow and its measurement

“…The Schwann cells should be mentioned in this context, since they seem to surround all islets in an envelope, but their functions remain enigmatic ( 7 ). It has been suggested that they may participate in regenerative processes after islet transplantation ( 8 ).…”

Pancreatic neuro-insular network in young mice revealed by 3D panoramic histology

“…Third, in mouse development, the pancreatic/islet sympathetic innervation is important for islet formation and functional maturation [12]. Fourth, in mouse islet transplantation, the engrafted islets are able to remodel the surrounding sympathetic nerves and the associated glial cells to regain the islet innervation patterns [13,14], suggesting an intrinsic ability of islets to recruit and associate with neural tissues.…”

PanIN-associated pericyte, glial, and islet remodeling in mice revealed by 3D pancreatic duct lesion histology

“…For example, mouse glial cells form a sheath in the mantle of an islet to envelop the neuroendocrine tissue (39). In the pancreatic vasculature, blood vessels consist of endothelium and pericytes (or mural cells) (24,34). The endothelium recruits pericytes through the release of the plateletderived growth factor to establish physical contact from the abluminal direction to stabilize the vascular system (27,43).…”