Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels
Source abstract
Abstract
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.
Source: europepmc · Quality: candidate unverified · Source record ↗
Research context
OpenAlex topics: Pancreatic function and diabetes · Genetics and Neurodevelopmental Disorders · Diabetes and associated disorders
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (65)
Show source-provided references
1. Prospects for research in diabetes mellitus10.1001/jama.285.5.628 ↗
2. The bioartificial pancreas: progress and challenges10.1089/dia.2005.7.968 ↗
3. Diabetes mellitus: an independent risk factor for stroke?10.1093/oxfordjournals.aje.a114934 ↗
4. Insulin-dependent diabetes mellitus and ischemic heart disease10.2337/diacare.8.1.S65 ↗
5. Lower-extremity amputation in people with diabetes. Epidemiol prevention10.2337/diacare.12.1.24 ↗
6. Diabetes and renal mortality in the United States10.2105/AJPH.75.11.1325 ↗
7. The incidence of vision loss in a diabetic population10.1016/S0161-6420(88)32991-X ↗
8. Long-term complications of diabetes mellitus10.1056/NEJM199306103282306 ↗
9. Geographic differences in the risk of insulin-dependent diabetes mellitus: the importance of registries10.2337/diacare.8.1.S101 ↗
10. Diabetes complications10.2337/diacare.27.6.1506 ↗
11. Biological and biomaterial approaches for improved islet transplantation10.1124/pr.58.2.6 ↗
12. Current advances and travails in islet transplantation10.2337/db09-0476 ↗
13. Islet transplantation as a treatment for diabetes – a work in progress10.1056/NEJMra032425 ↗
14. Advances in pancreatic islet transplantation in humans10.1111/j.1463-1326.2005.00476.x ↗
15. Cell loss in isolated human islets occurs by apoptosis10.1097/00006676-200004000-00008 ↗
16. Orientation of microvascular blood flow in pancreatic islet isografts10.1172/JCI117228 ↗
17. Vascularization of purified pancreatic islet-like cell aggregates (pseudoislets) after syngeneic transplantation10.2337/diabetes.47.4.559 ↗
18. Revascularization and function of pancreatic islet isografts in diabetic rats following transplantation10.3727/000000003108746993 ↗
19. Angiogenesis in cultured and cryopreserved pancreatic islet grafts10.1097/00007890-199706150-00020 ↗
20. Angiogenesis and vascularization of murine pancreatic islet isografts10.1097/00007890-199507000-00002 ↗
21. The endothelial cells in islets of langerhans10.3109/2000-1967-081 ↗
22. Hypoxia induces vascular endothelial growth factor gene and protein expression in cultured rat islet cells10.2337/diabetes.47.12.1894 ↗
23. Transplantation of isolated pancreatic islets into the portal vein of diabetic rats10.1038/244447a0 ↗
24. Markedly decreased oxygen tension in transplanted rat pancreatic islets irrespective of the implantation site10.2337/diabetes.50.3.489 ↗
25. Extended allograft survival of islets grafted into intra-abdominally placed testis10.2337/diab.33.4.405 ↗
26. The anterior chamber of the eye as a clinical transplantation site for the treatment of diabetes: a study in a baboon model of diabetes10.1007/s00125-011-2091-y ↗
27. A novel technique for the transplantation of pancreatic islets within a vascularized device into the greater omentum to achieve insulin independence10.1016/j.amjsurg.2011.02.009 ↗
28. One-stage reconstruction of infected cranial defects using a titanium mesh plate enclosed in an omental flap10.1097/01.sap.0000100898.68014.6f ↗
29. Revascularization of the entire heart by internal mammary artery implantation, epicardiectomy and free omental graft
30. Coerulospinal fiber regeneration in transected feline spinal cord10.1016/0361-9230(94)90153-8 ↗
31. Optimal implantation site for pancreatic islet transplantation10.1002/bjs.6391 ↗
32. A tripartite anoikis-like mechanism causes early isolated islet apoptosis10.1067/msy.2001.116413 ↗
33. Long-term culture of human pancreatic islets in an extracellular matrix: morphological and metabolic effects10.1016/0303-7207(93)90046-M ↗
34. Maintenance of beta-cell function and survival following islet isolation requires re-establishment of the islet–matrix relationship10.1677/joe.0.1630181 ↗
35. A novel approach to increase human islet cell mass while preserving beta-cell function10.2337/diabetes.51.12.3435 ↗
36. The internal structure of self-assembled peptide amphiphiles nanofibers10.1039/b614426h ↗
37. Intermolecular forces in the self-assembly of peptide amphiphile nanofibers10.1002/adfm.200500161 ↗
38. Bone regeneration mediated by biomimetic mineralization of a nanofiber matrix10.1016/j.biomaterials.2010.04.013 ↗
39. Multi-composite bioactive osteogenic sponges featuring mesenchymal stem cells, platelet-rich plasma, nanoporous silicon enclosures, and Peptide amphiphiles for rapid bone regeneration10.3390/jfb2020039 ↗
40. Cooperative effect of heparan sulfate and laminin mimetic peptide nanofibers on the promotion of neurite outgrowth10.1016/j.actbio.2012.02.006 ↗
41. Bioactive self-assembled peptide nanofibers for corneal stroma regeneration10.1016/j.actbio.2013.12.002 ↗
42. Self-assembly of peptide amphiphiles: from molecules to nanostructures to biomaterials10.1002/bip.21328 ↗
43. Heparin mimetic peptide nanofibers promote angiogenesis10.1021/bm200957s ↗
44. The effects of oral carvacrol treatment against H2O2 induced injury on isolated pancreas islet cells of rats10.4161/isl.25519 ↗
45. The incubation and monitoring of cell viability in primary rat islets of Langerhans and pancreatic beta-cell lines10.1007/978-1-59745-448-3_5 ↗
46. A practical guide to rodent islet isolation and assessment10.1007/s12575-009-9021-0 ↗
47. Growth factor binding on heparin mimetic peptide nanofibers10.1021/bm3010897 ↗
48. Proteomic analysis for the assessment of different lots of fetal bovine serum as a raw material for cell culture. Part IV. Application of proteomics to the manufacture of biological drugs10.1021/bp060121o ↗
49. Pancreatic islet culture and preservation strategies: advances, challenges, and future outlook10.3727/096368910X515872 ↗
50. Standard operating procedures for describing and performing metabolic tests of glucose homeostasis in mice10.1242/dmm.006239 ↗
51. Heparin and angiogenesis: size matters!10.1161/01.ATV.0000100563.16983.19 ↗
52. Self-assembly combining two bioactive peptide-amphiphile molecules into nanofibers by electrostatic attraction10.1021/ja028215r ↗
53. Computed circular dichroism spectra for the evaluation of protein conformation10.1021/bi00838a031 ↗
54. Extracellular matrix in pancreatic islets: relevance to scaffold design and transplantation10.3727/096368909788237195 ↗
55. Pancreatic islet cell survival following islet isolation: the role of cellular interactions in the pancreas10.1677/joe.0.1610357 ↗
56. Designer self-assembling peptide nanofiber scaffolds for adult mouse neural stem cell 3-dimensional cultures10.1371/journal.pone.0000119 ↗
57. The presence of transcription factors in fetal bovine sera10.1007/s11626-998-0101-2 ↗
58. Damage to porcine islets of langerhans after exposure to human blood in vitro, or after intraportal transplantation to cynomologus monkeys – protective effects of sCR1 and heparin10.1097/00007890-200003150-00007 ↗
59. Cellular basis of tissue regeneration by omentum10.1371/journal.pone.0038368 ↗
60. The effect of extracellular matrix components on the preservation of human islet function in vitro10.1016/j.biomaterials.2009.11.057 ↗
61. Alginate encapsulant incorporating CXCL12 Supports long-term Allo- and Xenoislet transplantation without systemic immune suppression10.1111/ajt.13049 ↗
62. Autocrine deactivation of macrophages in transgenic mice constitutively overexpressing IL-10 under control of the human CD68 promoter10.4049/jimmunol.168.7.3402 ↗
63. CXCL12 (SDF-1alpha) suppresses ongoing experimental autoimmune encephalomyelitis by selecting antigen-specific regulatory T cells10.1084/jem.20080730 ↗
64. Stromal cell derived factor-1 (SDF-1)/CXCL12 attenuates diabetes in mice and promotes pancreatic beta-cell survival by activation of the prosurvival kinase Akt10.2337/db07-0291 ↗
65. Stromal cell-derived factor-1 (SDF-1)/chemokine (C-X-C motif) receptor 4 (CXCR4) axis activation induces intra-islet glucagon-like peptide-1 (GLP-1) production and enhances beta cell survival10.1007/s00125-011-2181-x ↗