Extended Allograft Survival of Islets Grafted into Intra-abdominally Placed Testis

Selawry, Helena; Whittington, Karen B.

doi:10.2337/diab.33.4.405

Cited by 73 publications

(30 citation statements)

References 8 publications

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“…While the majority of the inhibitory activity is likely to be due to a protein or large peptide, it is not due to one of the TGF3 family isoforms known to be responsible for the majority of lymphocyte-inhibiting activity of cryptorchid testis extracts [13,59]. This study does not eliminate TGF3 as a regulatory factor in the adult testis; however, it does indicate that TGF3 may not be the major immunomodulatory activity responsible for immune privilege in the normal testis.…”

Section: Discussionmentioning

confidence: 68%

Immunoregulatory Activity in Adult Rat Testicular Interstitial Fluid: Roles of Interleukin-1 and Transforming Growth Factor β1

Hedger

Nikolic-Paterson

Hutchinson

et al. 1998

Biology of Reproduction

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Studies on the effect of rat testicular interstitial fluid (IF) on T-cell function have reported both stimulatory and inhibitory actions. Specific cytokines produced within the testis, particularly interleukin-1 (IL-1) and transforming growth factor beta (TGFbeta), may contribute to these apparently conflicting observations. In proliferation assays employing lectin- or antibody-activated thymocytes or mature T cells in vitro, adult rat testicular IF stimulated T-cell activation and/or proliferation at low assay doses and was inhibitory at higher doses. The stimulatory activity was blocked by recombinant IL-1 receptor antagonist. The inhibitory activity was not affected by a polyspecific TGFbeta antiserum. The biological characteristics of the inhibitor were distinct from those of a similar, but considerably less potent, activity in platelet-depleted serum. These data demonstrate that rat testicular IF contains biologically significant concentrations of IL-1 but has a predominantly inhibitory action on T-cell responses. The factor predominantly responsible for this inhibitory activity displays a relatively large apparent molecular weight, is protease sensitive and partially heat labile, but does not appear to be one of the known mammalian TGFbeta isoforms.

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Section: Discussionmentioning

confidence: 68%

Immunoregulatory Activity in Adult Rat Testicular Interstitial Fluid: Roles of Interleukin-1 and Transforming Growth Factor β1

Hedger

Nikolic-Paterson

Hutchinson

et al. 1998

Biology of Reproduction

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“…Sertoli cell expression of various mediators also is thought to create a localized immunosuppressive effect within the testis (18,59). The ability of Sertoli cells to modulate immune responses has been studied by cotransplanting them with other cells at ectopic sites, where Sertoli cells were found to protect and extend survival of such grafts (16,37,56,59,68). …”

Section: Introductionmentioning

confidence: 99%

Characterization and Functionality of Proliferative Human Sertoli Cells

et al. 2011

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It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2′-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility, reproductive toxicology, testicular cancer, and spermatogenesis, and due to their unique biological properties potentially could be useful in cell therapy.

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“…In rodent models, allogeneic islets survive and function when implanted into the anterior chamber of the eye or the intraabdominal (but not scrotal) testis (16,17). The mechanisms underlying the maintenance of immunoprivilege within these environments are not understood but may involve Fas ligand (18,19) and transforming growth factor ␤ (20).…”

mentioning

confidence: 99%

Long-term survival of intratesticular porcine islets in nonimmunosuppressed beagles

Gores¹,

Hayes

Copeland

et al. 2003

Transplantation

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Extended Allograft Survival of Islets Grafted into Intra-abdominally Placed Testis

Cited by 73 publications

References 8 publications

Immunoregulatory Activity in Adult Rat Testicular Interstitial Fluid: Roles of Interleukin-1 and Transforming Growth Factor β1

Immunoregulatory Activity in Adult Rat Testicular Interstitial Fluid: Roles of Interleukin-1 and Transforming Growth Factor β1

Characterization and Functionality of Proliferative Human Sertoli Cells

Long-term survival of intratesticular porcine islets in nonimmunosuppressed beagles

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