Reversal of hyperglycemia in diabetic mice by a marginal islet mass together with human blood outgrowth endothelial cells is independent of the delivery technique and blood clot-induced processes

Coppens, Violette; Heremans, Yves; Leuckx, Gunter; Suenens, Krista; Jacobs-Tulleneers-Thevissen, Daniel; Verdonck, Kristoff; Luttun, Aernout; Heimberg, Harry; Leu, Nico De

doi:10.4161/isl.26778

Cited by 3 publications

(6 citation statements)

References 16 publications

(34 reference statements)

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“…To circumvent this problem, excessive numbers of islets are routinely transplanted in both experimental and clinical settings. When strategies to improve islet viability are adopted, reduced numbers of transplanted islets have been shown to establish normoglycemia (21)(22)(23)(24). Recently, we reported the unusual localization of high levels of the complex sugar heparan sulfate (HS) inside beta cells in native islets in situ, the critical requirement of intracellular HS for beta cell survival and the loss of intraislet HS during islet isolation (25).…”

Section: Introductionmentioning

confidence: 99%

Islet Heparan Sulfate but Not Heparan Sulfate Proteoglycan Core Protein Is Lost During Islet Isolation and Undergoes Recovery Post-Islet Transplantation

Choong

Freeman

Parish

et al. 2015

American Journal of Transplantation

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Islet beta cells in situ express intracellular heparan sulfate (HS), a property previously shown in vitro to be important for their survival. We report that HS levels inside islet beta cells correlate with the novel intracel-lular localization of the HSPG core proteins for collagen type XVIII (Col18), a conventional extracellular matrix component. Syndecan-1 (Sdc1) and CD44 core proteins were similarly localized inside beta cells. During isolation, mouse islets selectively lose HS to 11-27% of normal levels but retain their HSPG core proteins. Intra-islet HS failed to recover substantially during culture for 4 days and was not reconstituted in vitro using HS mimetics. In contrast, significant recovery of intra-islet HS to $40-50% of normal levels occurred by 5-10 days after isotransplantation. Loss of islet HS during the isolation procedure is independent of heparanase (a HS-degrading endoglycosidase) and due, in part, to oxidative damage. Treatment with antioxidants reduced islet cell death by $60% and increased the HS content of isolated islets by $twofold compared to untreated islets, preserving intra-islet HS to $60% of the normal HS content of islets in situ. These findings suggest that the preservation of islet HS during the islet isolation process may optimize islet survival posttransplant. Abbreviations: AEC, 3-amino-9-ethylcarbazole; A.U., arbitrary units; B6.Hpse-KO, heparanase knockout C57BL/6; BHA, butylated hydroxyanisole; BM, basement membrane; Col18, collagen type XVIII; DMTU, dimethylthiourea; ECM, extracellular matrix; EXT1-2, exostosin 1-2; EXTL1-3, exostosin-like 1-3; FITC, fluo-rescein isothiocyanate; GMFR, geometric mean fluo-rescence ratio; Gpc2, glypican-2; H&E, haematoxylin and eosin; HS, heparan sulfate; HSPG, heparan sulfate proteoglycan; MFI, mean fluorescence intensity; MNCs, mononuclear cells; Ndst2, N-deacetylase/N-sulfotransferase 2; NOD/Lt, nonobese diabetic; PSN, penicillin-streptomycin-neomycin; qRT-PCR, quantitative reverse transcription polymerase chain reaction; ROS, reactive oxygen species; Sdc1, syndecan-1; SEM, standard error of the mean

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Section: Introductionmentioning

confidence: 99%

Islet Heparan Sulfate but Not Heparan Sulfate Proteoglycan Core Protein Is Lost During Islet Isolation and Undergoes Recovery Post-Islet Transplantation

Choong

Freeman

Parish

et al. 2015

American Journal of Transplantation

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“…ECFCs were derived predominantly from human umbilical cord blood (n = 55; 83%) while remaining studies expanded ECFCs from peripheral blood (n = 11; 17%) of healthy adult volunteers. [11][12][13][14][15][16][17][18][19][20][21] One study used ECFCs collected from human placenta. 22 Most (n = 59, 89%) studies administered ECFCs while 12 studies also included experiments with derivative products such as extracellular vesicles (ie, exosomes [23][24][25][26][27] or microvesicles 11,28 ), and/or conditioned media 7,[29][30][31][32] (Table 1).…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies

Liao

Zheng

Shorr

et al. 2020

Stem Cells Translational Medicine

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Endothelial colony-forming cells (ECFCs) hold significant promise as candidates for regenerative therapy of vascular injury. Existing studies remain largely preclinical and exhibit marked design heterogeneity. A systematic review of controlled preclinical trials of human ECFCs is needed to guide future study design and to accelerate clinical translation. A systematic search of Medline and EMBASE on 1 April 2019 returned 3131 unique entries of which 66 fulfilled the inclusion criteria. Most studies used ECFCs derived from umbilical cord or adult peripheral blood. Studies used genetically modified immunodeficient mice (n = 52) and/or rats (n = 16). ECFC phenotypes were inconsistently characterized. While >90% of studies used CD31+ and CD45−, CD14 − was demonstrated in 73% of studies, CD146+ in 42%, and CD10+ in 35%. Most disease models invoked ischemia. Peripheral vascular ischemia (n = 29), central nervous system ischemia (n = 14), connective tissue injury (n = 10), and cardiovascular ischemia and reperfusion injury (n = 7) were studied most commonly. Studies showed predominantly positive results; only 13 studies reported ≥1 outcome with null results, three reported only null results, and one reported harm. Quality assessment with SYRCLE revealed potential sources of bias in most studies. Preclinical ECFC studies are associated with benefit across several ischemic conditions in animal models, although combining results is limited by marked heterogeneity in study design. In particular, characterization of ECFCs varied and aspects of reporting introduced risk of bias in most studies. More studies with greater focus on standardized cell characterization and consistency of the disease model are needed.

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“…Although fibrin itself is able to the promote vascularization of islet grafts (J. S. Kim et al, ; J. Y. Lim et al, ), it is normally used in combination with proangiogenic growth factors, particularly when islets are transplanted at extrahepatic sites (Bhang et al, ; Najjar et al, ), or with synthetic materials such as PDMS (Brady et al, ). Blood plasma, which results in a cheaper and safer alternative to purified fibrin, has also been used in islet transplantation alone (Berman et al, ; Schaschkow et al, ) or in combination with accessory cells (Perez‐Basterrechea et al, ; Pérez‐Basterrechea, Obaya, Meana, Otero & Esteban, ; Pérez‐Basterrchea, et al, ; Coppens et al, ; Coppens et al, ), resulting in successful islet engraftment and allowing glycemia control in diabetic recipients. On the other hand, silk, obtained from both spiders and silkworm (Bombyxmori ), is another biocompatible, biodegradable, and versatile biomaterial used in tissue engineering (Jao, Mou, & Hu, ).…”

Section: Tissue Engineering In Islet Transplantationmentioning

confidence: 99%

“…Song et al, ) in micro‐ (Buitinga et al, ) and macro‐encapsulation approaches (Gupta & Sefton, ; Y. Li et al, ) or even when using EPCs as a cell sheet (Barba‐Gutierrez et al, ). Similar metabolic results were obtained when human blood outgrowth endothelial cells ( BOECs ) derived from the in vitro expansion of peripheral blood mononuclear cells were combined with islets (Coppens et al, ; Coppens et al, ).…”

Section: Tissue Engineering In Islet Transplantationmentioning

confidence: 99%

“…Moreover, these cells have been shown to increase graft revascularization and thus islet survival and glycemic control when simply cotransplanted with islets (Kang et al, 2012;Oh et al, 2013;Pan et al, 2011;Penko et al, 2015;Quaranta et al, 2014; in micro- (Buitinga et al, 2016) and macro-encapsulation approaches (Gupta & Sefton, 2011; or even when using EPCs as a cell sheet (Barba-Gutierrez et al, 2016). Similar metabolic results were obtained when human blood outgrowth endothelial cells (BOECs) derived from the in vitro expansion of peripheral blood mononuclear cells were combined with islets (Coppens et al, 2013a;Coppens et al, 2013b).…”

Section: Accessory Cellsmentioning

confidence: 99%

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Tissue‐engineering approaches in pancreatic islet transplantation

Pérez-Basterrechea

Esteban

Vega

et al. 2018

Biotech & Bioengineering

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Pancreatic islet transplantation is a promising alternative to whole-pancreas transplantation as a treatment of type 1 diabetes mellitus. This technique has been extensively developed during the past few years, with the main purpose of minimizing the complications arising from the standard protocols used in organ transplantation. By using a variety of strategies used in tissue engineering and regenerative medicine, pancreatic islets have been successfully introduced in host patients with different outcomes in terms of islet survival and functionality, as well as the desired normoglycemic control. Here, we describe and discuss those strategies to transplant islets together with different scaffolds, in combination with various cell types and diffusible factors, and always with the aim of reducing host immune response and achieving islet survival, regardless of the site of transplantation.

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Reversal of hyperglycemia in diabetic mice by a marginal islet mass together with human blood outgrowth endothelial cells is independent of the delivery technique and blood clot-induced processes

Abstract: Reversal of hyperglycemia in diabetic mice by a marginal islet mass together with human blood outgrowth endothelial cells is independent of the delivery technique and blood clot-induced processes, Islets,5:5,[196][197][198][199][200]

Cited by 3 publications

References 16 publications

Islet Heparan Sulfate but Not Heparan Sulfate Proteoglycan Core Protein Is Lost During Islet Isolation and Undergoes Recovery Post-Islet Transplantation

Islet Heparan Sulfate but Not Heparan Sulfate Proteoglycan Core Protein Is Lost During Islet Isolation and Undergoes Recovery Post-Islet Transplantation

Human endothelial colony-forming cells in regenerative therapy: A systematic review of controlled preclinical animal studies

Tissue‐engineering approaches in pancreatic islet transplantation

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