Neural crest stem cells increase beta cell proliferation and improve islet function in co-transplanted murine pancreatic islets

Abstract

Co-grafting of NCSCs with pancreatic islets improved insulin release in mixed transplants and enhanced beta cell proliferation, resulting in increased beta cell mass. This co-transplantation model offers an opportunity to restore neural-islet interactions and improve islet functions after transplantation.

Differentiating neural crest stem cells induce proliferation of cultured rodent islet beta cells

“…NCSCs induce proliferation of co-cultured primary islet beta cells NCSCs strongly increase islet cell proliferation when co-transplanted under the kidney capsule of mice [11]. These in vivo data did not distinguish between the direct effects of NCSCs on the islet cells and possible indirect effects through other, non-endocrine islet cell types, such as endothelial cells [21].…”

“…Furthermore, islets themselves induce migration and differentiation of NCSCs towards a neuronal phenotype both in vitro [10] and in vivo when the two cell types were transplanted under the kidney capsule [11]. Within a graft containing both NCSCs and islets, the beta cells display an increased proliferation [11]. In view of these findings, the current report describes the potential of NCSCs to induce beta cell proliferation in order to increase the glucose responsive beta cell mass.…”

“…We previously showed that mature sensory neurons influence insulin release by adult islets in vitro [10]. Furthermore, islets themselves induce migration and differentiation of NCSCs towards a neuronal phenotype both in vitro [10] and in vivo when the two cell types were transplanted under the kidney capsule [11]. Within a graft containing both NCSCs and islets, the beta cells display an increased proliferation [11].…”

Gene Therapy and Stem Cell Therapy to Improve the Outcome of Human Islet Transplantation

“…However, the blood glucose level of the mice transplanted with untransduced islets, Adv-LacZ transduced islets, and Adv-hXIAP plus embelin cotransduced islets gradually increased after the first week post transplantation, and was maintained to the diabetic level (~600 mg/dL) since 2 weeks post transplantation ( Figure 3-6), suggesting the impaired normoglycemic control caused by the impaired islet viability and function. This result is also consistent with previous reports [4,8,92]. In contrast, the mice transplanted with Adv-hXIAP showed prolonged normoglycemic control till 6 weeks post transplantation, probably due to the improvement in transplanted islet viability and function by XIAP overexpression.…”

Fabrication of Tissue-Engineered Vascular Grafts using Low Sustained Intraluminal Pressure to Sod Human Adipose-Derived Stromal Vascular Fraction Cells onto ePTFE

“…Tissue factor expression, which is involved in the activation of blood coagulation via the extrinsic pathway, of the sodded cells was measured to assess biological complications associated with pressure sodding. 21,22 Optimized vascular grafts were subsequently implanted into the carotid arteries of dogs and then observed for 140±1 days. Following explantation, the vascular grafts were evaluated for cell coverage and patency.…”