Effects of recipient mouse strain, sex and gonadal status on the outcome of testis tissue xenografting

2010 ◽  
Vol 22 (8) ◽  
pp. 1279 ◽  
Author(s):  
Sepideh Abbasi ◽  
Ali Honaramooz
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Seminiferous Tubules ◽  
Recipient Mouse ◽  
Immunodeficient Mice ◽  
Newborn Piglets ◽  
Female Nude ◽  
Different Strains ◽  
Gonadal Status ◽  
Testis Tissue

The aim of the present study was to examine factors that may affect the outcome of testis tissue xenografting. Recipient factors were examined by grafting small fragments of testis tissue from newborn piglets under the back skin of immunodeficient mice of different strains (severe combined immunodeficiency (SCID) v. nude), sex (male v. female) and gonadal status (intact v. gonadectomised) using a factorial design (eight groups; n = 7 mice per group). Recipient mice were killed after 8 months to compare the gross and histological attributes of the recovered grafts. Overall, approximately 94% of grafts were recovered. Gonadectomy of male or female recipients did not affect any of the measured outcomes of testis tissue xenografting, therefore data were pooled. Overall, in terms of sex, male mice and, in terms of strain, SCID mice tended to show higher gross and histological development of grafts. The group of female nude mice had the lowest graft recovery rate (75%) compared with the other groups (95–100%; P < 0.05). The grafts from male SCID mice were, on average the largest and had the highest percentage of spermatozoa-containing seminiferous tubules among all the groups (P < 0.05). These results suggest that male SCID mice provide a suitable recipient model for testis tissue xenografting and that the mice do not need to be castrated for optimal results.

305 OPTIMIZING DONOR AND RECIPIENT FACTORS IN XENOGRAFTING OF TESTIS TISSUE

2010 ◽  
Vol 22 (1) ◽  
pp. 308
Author(s):  
S. Abbasi ◽  
A. Honaramooz
Keyword(s):  
Recipient Mouse ◽  
Male Mice ◽  
Intact Female ◽  
Intact Male ◽  
Immunodeficient Mice ◽  
Female Nude ◽  
Graft Weight ◽  
And Gender ◽  
Gonadal Status ◽  
Testis Tissue

Grafting of donor mammalian testis tissue into recipient mice allows completion of spermatogenesis in the grafted tissue and therefore can serve as a new option for preservation of male germ line. For testis tissue xenografting, castrated male nude mice typically serve as recipients, each receiving 8 testis tissue fragments; however, no study has comprehensively investigated donor and recipient factors. The objective of this study was to determine the effects of strain of immunodeficient recipient mouse (nude v. SCID), gonadal status (intact v. gonadectomized), and gender (male v. female) on the outcome of testis tissue xenografting. A secondary objective was to determine the optimal number of testis tissue fragments per mouse most suitable for xenografting. Testis parenchyma from newborn piglets were cut into small fragments (5 mg each) and grafted under the back skin of different groups of immunodeficient mice. In Experiment 1, 8 groups of mice (n = 7/group) served as recipients: castrated male nude, intact male nude, ovariectomized female nude, intact female nude, castrated male SCID, intact male SCID, ovariectomized female SCID, and intact female SCID. In Experiment 2, 4 groups of mice (n = 10/group) served as recipients of 2, 4, 8, or 16 testis tissue fragments per mouse. Recipient mice were sacrificed 8 months after grafting and the weight of the grafts and vesicular glands (male mice) were compared among groups by analysis of variance. In Experiment 1, mouse gonadal status (intact v. gonadectomized) did not affect the total graft weight (P > 0.05), but both the recipient mouse strain (nude v. SCID) and gender (male v. female) affected the total graft weight (2460 ± 320.9, 1420 ± 290.0, 758 ± 156.7, and 2780 ± 297.4, mean ± SEM, P < 0.0001 for SCID, nude, female, and male mice, respectively). In Experiment 2, the total graft weight was highest in the group of mice receiving 8 testis tissue fragments (192 ± 76.1, 695 ± 96.5, 2443 ± 338.8, and 1458 ± 305.4, mean ± SEM, P < 0.0001 for 2, 4, 8, or 16 fragment groups, respectively). These results collectively indicate that male SCID mice receiving 8 testis tissue fragments provide optimized conditions for the recovery of largest grafts. Research was supported by grants from the Natural Sciences and Engineering Research Council of Canada (NSERC) and the Saskatchewan Health Research Foundation (SHRF) to A. Honaramooz and scholarships from the Western College of Veterinary Medicine and the International Peace Scholarship to S. Abbasi.

scholarly journals Full reconstitution of human platelets in humanized mice after macrophage depletion

Blood ◽  
2012 ◽  
Vol 120 (8) ◽  
pp. 1713-1716 ◽  
Author(s):  
Zheng Hu ◽  
Yong-Guang Yang
Keyword(s):  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Fetal Liver ◽  
Severe Combined Immunodeficiency ◽  
Human Platelets ◽  
Humanized Mice ◽  
Recipient Mouse ◽  
Immunodeficient Mice ◽  
Macrophage Depletion ◽  
Mouse Macrophages

Abstract Cotransplantation of human fetal thymic tissue and CD34+ fetal liver cells in nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) or NOD/SCID/γc−/− mice results in the development of multilineage human hematopoietic cells. In this study, we show that these humanized mice had extremely low levels of human platelets. The presence of human megakaryocytes at a normal concentration in the bone marrow suggests that human megakaryocytic differentiation occurred efficiently in these mice. Rapid increase in human platelets in blood to levels comparable with those of human peripheral blood mononuclear cells (PBMCs) after macrophage depletion indicates that mouse macrophages are responsible for the poor human platelet reconstitution in humanized mice. In support of this possibility, human platelets were rapidly rejected after infusion into untreated mice, but persisted in macrophage-depleted mice. These findings indicate that inhibition or depletion of recipient mouse macrophages may provide a useful means for evaluating human thrombopoiesis and platelet function in vivo using immunodeficient mice.

scholarly journals GH enhances proliferation of human hepatocytes grafted into immunodeficient mice with damaged liver

2007 ◽  
Vol 194 (3) ◽  
pp. 529-537 ◽  
Author(s):  
Norio Masumoto ◽  
Chise Tateno ◽  
Asato Tachibana ◽  
Rie Utoh ◽  
Yoshio Morikawa ◽  
...  
Keyword(s):  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Chimeric Mouse ◽  
Chimeric Mice ◽  
Immunodeficient Mice ◽  
Forkhead Box M1 ◽  
The Difference ◽  
Immunodeficiency Disease ◽  
Old Donor

We investigated effects of human (h) GH on the proliferation of h-hepatocytes that had been engrafted in the liver of albumin enhancer/promoter driven-urokinase plasminogen activator transgenic/severe combined immunodeficiency disease (uPA/SCID) mice (chimeric mice). The h-hepatocytes therein were considered to be deficient in GH, because hGH receptor (hGHR) is unresponsive to mouse GH. Actually, hIGF-1 was undetectable in chimeric mouse sera. The uPA/SCID mice were transplanted with h-hepatocytes from a 6-year (6Y)-old donor, and were injected with recombinant hGH (rhGH). rhGH stimulated the repopulation speed of h-hepatocytes; and up-regulated hIGF-1, human signal transducers and activators of transcription (hSTAT) 3, and cell cycle regulatory genes such as human forkhead box M1, human cell division cycle 25A, and human cyclin D1. To confirm the reproducibility of these effects of rhGH, similar experiments were run using h-hepatocytes from a 46-year (46Y)-old donor. rhGH similarly enhanced their repopulation speed and up-regulated the expression of the above-tested genes, especially hIGF-1 and hSTAT1. The extent of the enhancement by rhGH was much less than that in 6Y-hepatocyte-chimeric mice most probably due to the difference in GHR expression levels between the two donors. In conclusion, this study clearly demonstrated that rhGH stimulates the proliferation of h-hepatocytes in vivo.

scholarly journals Aberrant regulation of superantigen responses during T-cell reconstitution and graft-versus-host disease in immunodeficient mice

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2216-2224
Author(s):  
David Spaner ◽  
Xiaofang Sheng-Tanner ◽  
Andre C. Schuh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Adoptive Transfer ◽  
Scid Mice ◽  
Control Mechanisms ◽  
Activated T Cells ◽  
Host Disease ◽  
Immunodeficient Mice ◽  
Graft Versus Host

Acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation is associated with impaired deletion and anergy of host-reactive T cells. To elucidate the immunoregulatory events that may contribute to such dysregulated T-cell responses in GVHD, we studied superantigen (SAg) responses after adoptive T-cell transfer into severe combined immunodeficient (SCID) mice. SAg responses are normally regulated by mechanisms involving deletion and anergy, with SAg-reactive T cells typically being deleted rapidly in vivo. In a SCID mouse model of GVHD, however, allogeneic host SAg-reactive T cells were not deleted rapidly, but rather persisted in increased numbers for several months. Moreover, depending on the timing of SAg stimulation and the numbers of T cells transferred, dysregulation (impaired deletion and anergy) of SAg responses could be demonstrated following the adoptive transfer of syngeneic T cells into SCID mice as well. Transgenic T-cell receptor-bearing KJ1-26.1+ T cells were then used to determine the fate of weakly reactive T cells after adoptive transfer and SAg stimulation. When transferred alone, KJ1-26.1+ T cells demonstrated impaired deletion and anergy. In the presence of more strongly staphylococcal enterotoxin B (SEB)–reactive T cells, however, KJ1-26.1+ T cells were regulated normally, in a manner that could be prevented by inhibiting the effects of more strongly SEB-reactive cells or by increasing the level of activation of the KJ1-26.1+ T cells themselves. We suggest that the control mechanisms that normally regulate strongly activated T cells in immunocompetent animals are lost following adoptive transfer into immunodeficient hosts, and that this impairment contributes to the development of GVHD.

scholarly journals Phenotype and function of human hematopoietic cells engrafting immune- deficient CB17-severe combined immunodeficiency mice and nonobese diabetic-severe combined immunodeficiency mice after transplantation of human cord blood mononuclear cells

Blood ◽  
1996 ◽  
Vol 88 (10) ◽  
pp. 3731-3740 ◽  
Author(s):  
F Pflumio ◽  
B Izac ◽  
A Katz ◽  
LD Shultz ◽  
W Vainchenker ◽  
...  
Keyword(s):  
Cord Blood ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Severe Combined Immunodeficiency ◽  
Human Cells ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Human Cd34 ◽  
Blood Mononuclear Cells ◽  
Cord Blood Mononuclear Cells

In an attempt to understand better the regulation of stem cell function in chimeric immunodeficient mice transplanted with human cells, and the filiation between progenitor cells identified in vitro and in vivo, we assessed the different compartments of hematopoietic progenitors found in the marrow of CB17-severe combined immunodeficiency (SCID) mice (34 mice, 9 experiments) after intravenous injection of 2 to 3 x 10(7) cord blood mononuclear cells. On average 6.3 +/-4 x 10(5) human cells were detected per four long bones 4 to 6 weeks after the transplant predominantly represented by granulomonocytic (CD11b+) and B lymphoid (CD19+) cells. Twenty five percent of these human cells expressed the CD34 antigen, of which 90% coexpressed the CD38 antigen and 50% the CD19 antigen. Functional assessment of progenitor cells (both clonogenic and long-term culture-initiating cells [LTC-IC]) was performed after human CD34+ cells and CD34+/CD38- cells have been sorted from chimeric CB17-SCID marrow 3 to 10 weeks after intravenous (IV) injection of human cells. The frequency of both colony-forming cells and LTC-IC was low (4% and 0.4%, respectively in the CD34+ fraction) when compared with the frequencies of cells with similar function in CD34+ cells from the starting cord blood mononuclear cells (26% +/- 7% and 7.2% +/- 5%, respectively). More surprisingly, the frequency of LTC-IC was also low in the human CD34+ CD38- fraction sorted from chimeric mice. This observation might be partly accounted for by the expansion of the CD34+ CD19+ B-cell precursor compartment. Despite their decreased frequency and absolute numbers, the differentiation capability of these LTC-IC, assessed by their clonogenic progeny output after 5 weeks in coculture with murine stromal cells was intact when compared with that of input LTC-IC. Furthermore the ratio between clonogenic progenitor cells and LTC-IC was similar in severe combined immunodeficiency (SCID) mice studied 4 weeks after transplant and in adult marrow or cord blood suspensions. Results generated in experiments where nonobese diabetic (NOD)-SCID mice were used as recipients indicate a higher level of engraftment but no change in the distribution of clonogenic cells or LTC-IC. These results suggest that the hierarchy of hematopoietic differentiation classically defined in human hematopoietic tissues can be reconstituted in immunodeficient SCID or NOD-SCID mice.

Epithelial stem cell-mediated development of the human respiratory mucosa in SCID mice

2000 ◽  
Vol 113 (5) ◽  
pp. 767-778 ◽  
Author(s):  
A. Delplanque ◽  
C. Coraux ◽  
R. Tirouvanziam ◽  
I. Khazaal ◽  
E. Puchelle ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Sex Chromosome ◽  
Severe Combined Immunodeficiency ◽  
Scid Mice ◽  
Functional Assay ◽  
Combined Immunodeficiency ◽  
Freezing And Thawing ◽  
Normal Epithelium ◽  
Tracheobronchial Epithelium

We have developed an in vivo assay for progenitor cells of the human tracheobronchial epithelium relying on the transplantation of human prenatal respiratory tissues into severe combined immunodeficiency mice. Engrafted embryonic or fetal open tracheobronchial rudiments are rapidly closed at each end by a neoformed membrane that we named the operculum. After 2–4 weeks, differentiated human respiratory epithelium covers both the native airway matrix and the new operculum. Human epithelial cells dissociated from either emerging embryonic lung primordia or mature xenografts were seeded in host human airway grafts, of which native epithelium had been eliminated by several cycles of freezing and thawing. All grafts seeded with donor epithelial cells and implanted back into SCID mice recovered a surface mucociliary epithelium expressing expected markers and secreting mucus. Spontaneous epithelium regrowth was never observed in control unseeded, denuded grafts. In some experiments, donor epithelial cells and host denuded airway were sex-mismatched and the donor origin of newly formed epithelial structures was confirmed by sex chromosome detection. After two rounds of seeding and reimplantation, a normal epithelium was observed to line the 3rd generation operculum. These observations substantiate a functional assay for human candidate airway epithelium stem cells.

scholarly journals Eradication of minimal disease in severe combined immunodeficient mice with disseminated Daudi lymphoma using chemotherapy and an immunotoxin cocktail

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 702-707 ◽  
Author(s):  
MA Ghetie ◽  
K Tucker ◽  
J Richardson ◽  
JW Uhr ◽  
ES Vitetta
Keyword(s):  
Scid Mice ◽  
Histopathologic Examination ◽  
Lymphoma Cell Line ◽  
Chemotherapeutic Drugs ◽  
Conventional Chemotherapy ◽  
Ricin A Chain ◽  
Immunodeficient Mice ◽  
Minimal Disease ◽  
A Chain ◽  
Ricin A

Abstract Severe combined immunodeficient (SCID) mice injected intravenously with a human Burkitt's lymphoma cell line (Daudi) develop disseminated lymphoma (SCID/Daudi), which is fatal in 100% of the mice. Early treatment of these mice with either an immunotoxin (IT) cocktail (consisting of anti-CD19-ricin A chain plus anti-CD22-ricin A chain) or chemotherapy significantly prolonged survival but was not curative. Combination therapy with the IT cocktail and any one of three chemotherapeutic drugs (doxorubicin, cytoxan, or camptothecin) cured the mice. Cure was demonstrated by both histopathologic examination of treated mice and, more importantly, by adoptive transfer of cells from organs of the cured mice to naive SCID mice where 100 tumor cells would have caused disease in the recipients. These results provide a strong rationale for combining IT therapy with conventional chemotherapy in the treatment of B-cell neoplasia.

scholarly journals Immunotherapy of Multiple Myeloma With a Monoclonal Antibody Directed Against a Plasma Cell-Specific Antigen, HM1.24

Blood ◽  
1997 ◽  
Vol 90 (8) ◽  
pp. 3179-3186 ◽  
Author(s):  
Shuji Ozaki ◽  
Masaaki Kosaka ◽  
Shingo Wakatsuki ◽  
Masahiro Abe ◽  
Yasuo Koishihara ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Antibody ◽  
Plasma Cell ◽  
Severe Combined Immunodeficiency ◽  
Specific Antigen ◽  
Chemotherapeutic Agents ◽  
Scid Mice ◽  
Dependent Manner ◽  
Rpmi 8226

Abstract Multiple myeloma remains an incurable malignancy because of marked resistance of tumor cells to conventional chemotherapeutic agents. Alternative strategies are needed to solve these problems. To develop a new strategy, we have generated a monoclonal antibody (MoAb), which detects a human plasma cell-specific antigen, HM1.24. In this report, we evaluated the in vivo antitumor effect of unconjugated anti-HM1.24 MoAb on human myeloma xenografts implanted into severe combined immunodeficiency (SCID) mice. Two models of disseminated or localized tumors were established in SCID mice by either intravenous or subcutaneous injection of human myeloma cell lines, ARH-77 and RPMI 8226. When mice were treated with a single intraperitoneal injection of anti-HM1.24 MoAb 1 day after tumor inoculation, the development of disseminated myeloma was completely inhibited. In mice bearing advanced tumors, multiple injections of anti-HM1.24 MoAb reduced the tumor size and significantly prolonged survival, including tumor cure, in a dose-dependent manner. The proliferation of cultured human myeloma cells was inhibited in vitro by anti-HM1.24 IgG-mediated complement-dependent cytotoxicity, but not by the antibody alone. Moreover, spleen cells from SCID mice mediated antibody-dependent cell cytotoxicity against RPMI 8226 cells. These results indicate that anti-HM1.24 MoAb can be used for immunotherapy of multiple myeloma and related plasma cell dyscrasias.

scholarly journals Generation of biliary lesions after transfer of human lymphocytes into severe combined immunodeficient (SCID) mice.

1989 ◽  
Vol 170 (6) ◽  
pp. 1919-1930 ◽  
Author(s):  
S M Krams ◽  
K Dorshkind ◽  
M E Gershwin
Keyword(s):  
Bile Duct ◽  
Human Lymphocytes ◽  
Severe Combined Immunodeficiency ◽  
Serum Levels ◽  
Scid Mice ◽  
Lymphoid Cells ◽  
Biliary Cirrhosis ◽  
Human Mononuclear Cell ◽  
Mononuclear Infiltrate ◽  
Immunodeficiency Disease

Human PBL have been reported to reconstitute B and T cells as well as human serum Ig in mice with severe combined immunodeficiency disease (SCID). To confirm these observations and attempt the transfer of an autoimmune disease to the immunodeficient animals, groups of SCID mice received an injection of PBL from patients with primary biliary cirrhosis (PBC) or from normal volunteers. By 8 wk after the injection of 10-42 x 10(6) PBL into the mice, human lymphoid cells were detected in the spleen of approximately half of the animals and all had detectable serum levels of human IgG. Moreover, the sera of SCID mice that received cells from patients with PBC contained human antimitochondrial antibodies (AMA) to dihydrolipoamide acetyltransferase, the major mitochondrial autoantigen of PBC. Histologically, a human mononuclear cell infiltrate was present around the portal areas of the liver and inflammation, bile duct atypica, and necrosis of bile duct cells were observed. While the biliary lesions in the SCID recipients of PBC cells were more severe, a mononuclear infiltrate was clearly evident in mice that received cells from normal donors, suggesting the presence of a graft-vs.-host-like disease. While these data are the first to describe an animal model with both the humoral and cellular characteristics of PBC, they also raise an interesting question regarding the preferential localization of lymphoid cells to the biliary system.

scholarly journals High frequency of normal DJH joints in B cell progenitors in severe combined immunodeficiency mice.

1993 ◽  
Vol 178 (3) ◽  
pp. 1007-1016 ◽  
Author(s):  
J L Pennycook ◽  
Y Chang ◽  
J Celler ◽  
R A Phillips ◽  
G E Wu
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Fetal Liver ◽  
Severe Combined Immunodeficiency ◽  
Cell Activity ◽  
Scid Mice ◽  
Combined Immunodeficiency ◽  
Cell Stage ◽  
Reading Frame ◽  
B Lineage

The severe combined immunodeficiency (scid) mouse has a defective V(D)J recombinase activity that results in arrested lymphoid development at the pro-B cell stage in the B lineage. The defect is not absolute and scid mice do attempt gene rearrangement. Indeed, approximately 15% of all scid mice develop detectable levels of oligoclonal serum immunoglobulin and T cell activity. To gain more insight into the scid defect and its effect on V(D)J rearrangement, we analyzed DJH recombination in scid bone marrow. We determined that DJH structures are present in scid bone marrow and occur at a frequency only 10-100 times less than C.B-17+/+. The scid DJH repertoire is limited and resembles fetal liver DJH junctions, with few N insertions and predominant usage of reading frame 1. Moreover, 70% of the DJH structures were potentially productive, indicating that normal V(D)J recombinants should be arising continually.

Sign in / Sign up

Export Citation Format

Share Document