BACKGROUND: Nerve growth factor (NGF) has been reported to play an important regulatory role in pancreatic beta-cell function. However, the usefulness of NGF in a transplantation setting is unknown. METHODS: A marginal number of islet cells (260 islet equivalents/recipient) cultured for 24 hr with NGF (500 ng/ml) was syngeneically transplanted under the kidney capsule of streptozotocin-induced diabetic Balb/c mice. Fluorescence microscopy was used to evaluate islet viability. Islet function was evaluated in vitro and in vivo by static assay and glucose tolerance test, respectively. RESULTS: In vitro, improved viability and survival were found in murine islets cultured in serum-free medium for 96 hr with 500 ng/ml NGF (P<0.05). NGF-treated islets had more insulin secretion than islets cultured without NGF in response to 2.8 mmol/L glucose (P<0.05), and 20 mmol/L glucose conditions. In vivo, 67% of recipients with a submarginal number of islets cultured in NGF attained normoglycemia for more than 120 days, whereas transplanted islets without NGF treatment survived a maximum of 13 days in control mice. At posttransplant day 4, recipients of NGF-cultured islets showed significant improvement of glucose tolerance. On immunohistochemistry, the kidney capsules containing NGF-cultured islets displayed higher insulin content, and more dilated neoplastic microvessels than control renal capsules. The number of apoptotic cells using TUNEL staining decreased by nearly 50% in NGF-cultured islet grafts in comparison to control islet grafts. CONCLUSIONS: The above data suggest potential advantages of NGF for islet survival following transplantation. This neurotrophic approach may prove beneficial in human islet transplantation.
BACKGROUND: Nerve growth factor (NGF) has been reported to play an important regulatory role in pancreatic beta-cell function. However, the usefulness of NGF in a transplantation setting is unknown. METHODS: A marginal number of islet cells (260 islet equivalents/recipient) cultured for 24 hr with NGF (500 ng/ml) was syngeneically transplanted under the kidney capsule of streptozotocin-induced diabetic Balb/c mice. Fluorescence microscopy was used to evaluate islet viability. Islet function was evaluated in vitro and in vivo by static assay and glucose tolerance test, respectively. RESULTS: In vitro, improved viability and survival were found in murine islets cultured in serum-free medium for 96 hr with 500 ng/ml NGF (P<0.05). NGF-treated islets had more insulin secretion than islets cultured without NGF in response to 2.8 mmol/L glucose (P<0.05), and 20 mmol/L glucose conditions. In vivo, 67% of recipients with a submarginal number of islets cultured in NGF attained normoglycemia for more than 120 days, whereas transplanted islets without NGF treatment survived a maximum of 13 days in control mice. At posttransplant day 4, recipients of NGF-cultured islets showed significant improvement of glucose tolerance. On immunohistochemistry, the kidney capsules containing NGF-cultured islets displayed higher insulin content, and more dilated neoplastic microvessels than control renal capsules. The number of apoptotic cells using TUNEL staining decreased by nearly 50% in NGF-cultured islet grafts in comparison to control islet grafts. CONCLUSIONS: The above data suggest potential advantages of NGF for islet survival following transplantation. This neurotrophic approach may prove beneficial in human islet transplantation.
Authors: Nathaniel K Chan; Andre Obenaus; Annie Tan; Naoaki Sakata; John Mace; Ricardo Peverini; Richard Chinnock; Lawrence C Sowers; Eba Hathout Journal: Islets Date: 2009-11 Impact factor: 2.694
Authors: Eba Hathout; Lawrence Sowers; Rong Wang; Annie Tan; John Mace; Ricardo Peverini; Richard Chinnock; Andre Obenaus Journal: Transpl Int Date: 2007-09-10 Impact factor: 3.782
Authors: Simon M Mwangi; Yousef Usta; Nikrad Shahnavaz; Irene Joseph; Jose Avila; Jose Cano; Veerappa K Chetty; Christian P Larsen; Shanthi V Sitaraman; Shanthi Srinivasan Journal: Transplantation Date: 2011-10-15 Impact factor: 4.939
Authors: G Grouwels; S Vasylovska; J Olerud; G Leuckx; A Ngamjariyawat; Y Yuchi; L Jansson; M Van de Casteele; E N Kozlova; H Heimberg Journal: Diabetologia Date: 2012-05-23 Impact factor: 10.122