title: New alginate microcapsule system for angiogenic protein delivery and immunoisolation of islets for transplantation in the rat omentum pouch.
abstract: Severe hypoxia caused by a lack of vascular supply and an inability to retrieve encapsulated islets transplanted in the peritoneal cavity for biopsy and subsequent evaluation are obstacles to clinical application of encapsulation strategies for islet transplantation. We recently proposed an omentum pouch model as an alternative site of encapsulated islet transplantation and have also described a multi-layer microcapsule system suitable for coencapsulation of islets with angiogenic protein in which the latter could be encapsulated in an external layer to induce vascularization of the encapsulated islet graft. The purpose of the present study was to determine the angiogenic efficacy of fibroblast growth factor (FGF-1) released from the external layer of the new capsule system in the omentum pouch graft. We prepared 2 groups of alginate microspheres, each measuring ∼600 μm in diameter with a semipermeable poly-L-ornithine (PLO) membrane separating 2 alginate layers. While one group of microcapsules contained no protein (control), FGF-1 (1.794 μg/100 microcapsules) was encapsulated in the external layer of the other (test) group. From each of the 2 groups, 100 microcapsules were transplanted separately in an omentum pouch created in each normal Lewis rat and were retrieved after 14 days for analysis of vessel density using the technique of serial sample sections stained for CD31 with quantitative three-dimensional imaging. We found that FGF-1 released from the external layer of the test microcapsules induced a mean ± SD vessel density (mm(2)) of 198.8 ± 59.2 compared with a density of 128.9 ± 10.9 in pouches measured in control capsule implants (P = .03; n = 5 animals/group). We concluded that the external layer of our new alginate microcapsule system is an effective drug delivery device for enhancement of graft neovascularization in a retrievable omentum pouch.
authors.affiliation: Institute for Regenerative Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: McQuilling
authors.forename: J
authors.initials: J
authors.lastname: Arenas-Herrera
authors.forename: C
authors.initials: C
authors.lastname: Childers
authors.forename: R A
authors.initials: RA
authors.lastname: Pareta
authors.forename: O
authors.initials: O
authors.lastname: Khanna
authors.forename: B
authors.initials: B
authors.lastname: Jiang
authors.forename: E M
authors.initials: EM
authors.lastname: Brey
authors.forename: A C
authors.initials: AC
authors.lastname: Farney
authors.forename: E C
authors.initials: EC
authors.lastname: Opara
mesh_terms: D000464:Alginates / Q000737:chemistry*; D042501:Angiogenic Proteins / Q000737:chemistry*; D000818:Animals; D001706:Biopsy; D002214:Capsules / Q000737:chemistry*; D016503:Drug Delivery Systems; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D000860:Hypoxia; D007150:Immunohistochemistry / Q000379:methods; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008863:Microspheres; D018919:Neovascularization, Physiologic; D009852:Omentum / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D000464:Alginates; D042501:Angiogenic Proteins; D002214:Capsules; D006603:Hexuronic Acids; D010455:Peptides; D016220:Fibroblast Growth Factor 1; C008973:polyornithine; D020723:Glucuronic Acid
references.citation: J Surg Res. 2010 May 15;160(2):208-12
references.pmid: 19959194
references.citation: Diabetes Care. 2006 Jan;29(1):137-8
references.pmid: 16373911
references.citation: J Investig Med. 2010 Oct;58(7):831-7
references.pmid: 20683347
references.citation: Diabetes. 2010 Jun;59(6):1285-91
references.pmid: 20508222
references.citation: Transplantation. 2008 Feb 15;85(3):331-7
references.pmid: 18301328
references.citation: N Engl J Med. 2000 Jul 27;343(4):230-8
references.pmid: 10911004
references.citation: Am J Transplant. 2003 Mar;3(3):281-5
references.pmid: 12614282
references.citation: Diabetologia. 1983 Jul;25(1):45-50
references.pmid: 6350083
references.citation: Transplantation. 2006 May 15;81(9):1345-53
references.pmid: 16699465
references.citation: Xenotransplantation. 2007 Mar;14(2):157-61
references.pmid: 17381690
references.citation: J Clin Invest. 1996 Sep 15;98(6):1417-22
references.pmid: 8823307
references.citation: Science. 1980 Nov 21;210(4472):908-10
references.pmid: 6776628
references.citation: Transplantation. 1992 Nov;54(5):769-74
references.pmid: 1440841
references.citation: Am J Surg. 2010 Nov;200(5):655-8
references.pmid: 21056148
references.citation: Lancet. 1994 Apr 16;343(8903):950-1
references.pmid: 7909011
references.citation: J Biomed Mater Res A. 2010 Nov;95(2):632-40
references.pmid: 20725969