Reestablishment of microenvironment is necessary to maintain in vitro and in vivo human islet function.
Islet transplantation is associated with an elevated rate of early graft failure. The isolation process leads to structural and functional abnormalities. The reestablishment of the cell-matrix relationship is important to modulate the survival and function of islets. Thus, we evaluated the effect of human fibronectin (hFN) and self-assembling peptide nanofiber (SAPNF) in the ability to support islet function in vitro and after transplantation into streptozotocin (STZ)-induced diabetic severe combined immunodeficiency (SCID) mice. Human isolated islets were cultured with hFN or SAPNF for 7 days. Their ability to maintain insulin production/glucose responsiveness over time was evaluated. Islets embedded in hFN, SAPNF, or alone were transplanted into STZ-induced diabetic SCID mice. Islet grafts were removed after 14 days to evaluate insulin content, insulin expression, and apoptosis. SAPNF-entrapped islets maintained satisfactory morphology/viability and capability of glucose-dependent insulin secretion for over 7 days, whereas islets cultured in hFN underwent widespread deterioration. In vivo grafts containing human islets in SAPNF showed remarkably higher insulin content and expression when compared with human islets in hFn or alone. RT-PCR revealed lower caspase-3 expression in SAPNF islets grafts. These studies indicate that the reestablishment of the cell-matrix interactions by a synthetic matrix in the immediate postisolation period is a useful tool to maintain islet functions in vitro and in vivo.
Navarro-Alvarez
Nalú
N
Department of Surgery, Okayama University Graduate School of Medicine and Dentistry, Okayama 700-8558, Japan.
Rivas-Carrillo
Jorge David
JD
Soto-Gutierrez
Alejandro
A
Yuasa
Takeshi
T
Okitsu
Teru
T
Noguchi
Hirofumi
H
Matsumoto
Shinichi
S
Takei
Jiro
J
Tanaka
Noriaki
N
Kobayashi
Naoya
N
D000818:Animals; D017209:Apoptosis; D003921:Diabetes Mellitus, Experimental / Q000601:surgery*; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery; D005353:Fibronectins; D005947:Glucose / Q000378:metabolism; D006085:Graft Survival; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000473:pathology / Q000502:physiology; D016381:Islets of Langerhans Transplantation; D051379:Mice; D016513:Mice, SCID; D009926:Organ Preservation / Q000379:methods; D010446:Peptide Fragments; D054457:Tissue Scaffolds; D014183:Transplantation, Heterologous
D005353:Fibronectins; D007328:Insulin; D010446:Peptide Fragments; D005947:Glucose