Xenograft Research Articles

Racial differences in attitudes to clinical pig organ Xenotransplantation.

In addition to an organ donor shortage, racial disparities exist at different stages of the transplantation process. Xenotransplantation (XTx) could alleviate these issues. This study describes racial differences in attitudes to XTx among populations who may need a transplant or are transplant recipients. A Likert-scale survey was distributed at outpatient clinics to parents of children with congenital heart disease (CHD) and kidney patients on their attitudes to pig organ XTx. Data from these two groups were stratified by race and compared. Ninety-seven parents of children with CHD (74.2% White and 25.8% Black) and 148 kidney patients (50% White and 50% Black) responded to our survey. Black kidney patients' acceptance of XTx although high (70%) was lower than White kidney patients (91%; P .003). White kidney patients were more likely to accept XTx if results are similar to allotransplantation (OR 4.14; 95% CI 4.51-11.41), and less likely to be concerned with psychosocial changes when compared to Black kidney patients (receiving a pig organ would change your personality OR 0.08; 95% CI 0.01-0.67 and would change social interaction OR 0.24; 95% CI 0.07-0.78). There were no racial differences in attitudes to XTx among parents of children with CHD. There are differences in attitudes to XTx particularly among Black kidney patients. Because kidneys may be the first organ for clinical trials of XTx, future studies that decrease scientific mistrust and XTx concerns among the Black community are needed to prevent disparities in uptake of possible future organ transplant alternatives.

Role Of Mesiodens In The Etiology Of Midline Diastema

Role Of Mesiodens In The Etiology Of Midline Diastema

The resurgent landscape of xenotransplantation of pig organs in nonhuman primates

Organ shortage is a major bottleneck in allotransplantation and causes many wait-listed patients to die or become too sick for transplantation. Genetically engineered pigs have been discussed as a potential alternative to allogeneic donor organs. Although xenotransplantation of pig-derived organs in nonhuman primates (NHPs) has shown sequential advances in recent years, there are still underlying problems that need to be completely addressed before clinical applications, including (i) acute humoral xenograft rejection; (ii) acute cellular rejection; (iii) dysregulation of coagulation and inflammation; (iv) physiological incompatibility; and (v) cross-species infection. Moreover, various genetic modifications to the pig donor need to be fully characterized, with the aim of identifying the ideal transgene combination for upcoming clinical trials. In addition, suitable pretransplant screening methods need to be confirmed for optimal donor-recipient matching, ensuring a good outcome from xenotransplantation. Herein, we summarize the understanding of organ xenotransplantation in pigs-to-NHPs and highlight the current status and recent progress in extending the survival time of pig xenografts and recipients. We also discuss practical strategies for overcoming the obstacles to xenotransplantation mentioned above to further advance transplantation of pig organs in the clinic.

Corrigendum: Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer.

Corrigendum: Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer.

Cytokine-inducible promoters to drive dynamic transgene expression: The "Smart Graft" strategy.

Ubiquitous expression of T-cell regulatory transgenes such as the cytotoxic T lymphocyte-associated antigen 4 (CTLA4) or the high-affinity variant LEA29Y improves xeno graft survival. Such donor pigs are however immunocompromised and susceptible to infection. Continous high expression of CTLA4 or LEA29Y in the graft could also compromise the health status of recipients. The novel "Smart Graft" strategy is likely to avoid these problems by controlling the expression of T-cell regulatory transgenes as and when required. Candidate promoters inducible by inflammatory cytokines were identified by in silico screening for potential NF-κB binding sites. Basal promoter levels and responsiveness to TNFα and IL1ß were quantified by expression of secreted embryonic alkaline phosphatase in cultured cells. Promoters were modified to increase responsiveness by removing regulatory elements or adding SP-1 or NF-κB binding sites and again tested in vitro. The most promising promoters were then assessed in vivo. Porcine cells expressing inducible Renilla luciferase constructs were transplanted into immunodeficient NOD-Scid-IL2 receptor gammanull (NSG) mice. Following engraftment, the recipient's immune system was reconstituted by splenocyte transfer raising an immune response to the porcine xenograft. The resulting induction of promoter activity was detected by in vivo bioimaging. Three human (hTNFAIP1, hVCAM1 and hCCL2), and one porcine promoter (pA20) were chosen for in vitro tests. In all experiments, the semi-synthetic and inducible ELAM promoter as well as the CAG promoter were used as references. In contrast to hTNFAIP1 and hVCAM1 the ELAM, hCCL2 and pA20 promoters showed significant induction after cytokine challenge. The hCCL2 and pA20 promoters were further optimized, resulting in increased responsiveness to TNFα and IL1ß. Cytokine-dependent upregulation of promoter activity was tested in vivo, where the ELAM and the optimized hCCL2 promoters showed a 2-fold upregulation, while one of the improved A20 promoters showed almost 10-fold upregulation. Our results also revealed more than 4-fold cytokine inducibility of the CAG promoter. This is the first in vivo comparison of existing and newly designed cytokine-inducible promoters. Optimization of promoter structure resulted in almost 10-fold inducibility of promoter activity. Such a rapid and dynamically regulated response to inflammation and cell damage could reduce initial graft rejection, making the "Smart Graft" approach a useful means of modulating the expression of immune regulatory transgenes to avoid deleterious effects on porcine and human health. Expressing transgenes in this fashion could provide a safer organ for transplantation.

Invited Commentary: Xenotransplantation: Back to the Future?

Invited Commentary: Xenotransplantation: Back to the Future?

Old World Monkeys are less than ideal transplantation models for testing pig organs lacking three carbohydrate antigens (Triple-Knockout)

Triple-knockout (TKO) pigs (with added protective human transgenes) are likely to be optimal sources of organs for clinical organ xenotransplantation because many humans have minimal or no natural antibody to TKO pig cells. However, Old World monkeys (OWMs) have naturally-existing antibodies directed to TKO cells. We measured anti-pig IgM/IgG binding, and complement-dependent cytotoxicity to wild-type (WT), α1,3-galactosyltransferase gene-knockout (GTKO), and TKO pig peripheral blood mononuclear cells (PBMCs) using sera from humans, several OWMs, and two New World monkeys (NWMs). Furthermore, we compared survival of GTKO (n = 5) and TKO (n = 3) pig kidneys in baboons. OWMs had significantly greater IgM binding and cytotoxicity to TKO PBMCs than humans or NWMs. Mean anti-TKO IgM was significantly higher in OWMs and significantly lower in NWMs than in humans. Cytotoxicity of OWM sera to TKO PBMCs was significantly greater than of human serum, but there was no significant difference between human and NWM sera. The median survival of TKO pig kidneys (4 days) in baboons was significantly shorter than that of GTKO kidneys (136 days) (p < 0.05). Even though considered ideal for clinical xenotransplantation, the presence of naturally-existing antibodies to TKO pig cells in OWMs complicates the transplantation of TKO pig kidneys in OWMs.

CXCR4-STAT3 Axis Plays a Role in Tumor Cell Infiltration in an Orthotopic Mouse Glioblastoma Model.

Glioblastoma multiforme (GBM) is a fatal malignant tumor that is characterized by diffusive growth of tumor cells into the surrounding brain parenchyma. However, the diffusive nature of GBM and its relationship with the tumor microenvironment (TME) is still unknown. Here, we investigated the interactions of GBM with the surrounding microenvironment in orthotopic xenograft animal models using two human glioma cell lines, U87 and LN229. The GBM cells in our model showed different features on the aspects of cell growth rate during their development, dispersive nature of glioma tumor cells along blood vessels, and invasion into the brain parenchyma. Our results indicated that these differences in the two models are in part due to differences in the expression of CXCR4 and STAT3, both of which play an important role in tumor progression. In addition, the GBM shows considerable accumulation of resident microglia and peripheral macrophages, but polarizes differently into tumor-supporting cells. These results suggest that the intrinsic factors of GBM and their interaction with the TME determine the diffusive nature and probably the responsiveness to non-cancer cells in the TME.

Simvastatin induces apoptosis of nasopharyngeal carcinoma cells through NF-κB signaling pathway.

The aim of this study was to investigate the mechanism of simvastatin-induced apoptosis in nasopharyngeal carcinoma (NPC) cells. CNE1 and HK1 cell lines were treated with different concentrations of simvastatin for different time course. Subsequently, Cell Counting Kit-8 (CCK-8), colony formation assay, and flow cytometry were conducted to evaluate cell activity, colony formation ability, as well as cell cycle of NPC cells, respectively. The mRNA expressions of p21, Bim, and cyclin D1 were examined by qPCR. Meanwhile, the protein expression levels of apoptosis-related proteins (including caspase-3, Bax, Bcl-2) were detected by Western blot. Caspase-3 activity was determined to estimate cell apoptosis. An NPC xenotransplantation model was constructed to further determine the role of simvastatin in vivo. In addition, NF-κB activity was assessed through Luciferase reporter gene assay and Western blot. Simvastatin treatment lead to significantly reduced viability of NPC cells and the number of cell colonies dose-dependently and time-dependently. Meanwhile, simvastatin treatment caused cell cycle arrest in G0/G1 phase, remarkably downregulated expression of cyclin D1, and upregulated expressions of p21 and Bim. In addition, simvastatin induced apoptosis of NPC cells and enhanced the Luciferase activity of caspase-3. Western blot results indicated that simvastatin promoted the protein level of Bax and caspase-3, whereas suppressed the protein expression of Bcl-2. In vivo experiments showed that simvastatin was able to suppress the growth of NPC cells. Further studies demonstrated that simvastatin remarkably attenuated the Luciferase activity of pNF-κB-Luc, thereby specifically inhibiting the NF-κB signaling pathway. Simvastatin inhibits proliferation and promotes apoptosis of NPC cells by inhibiting the NF-κB pathway.

Solid organ xenotransplantation at the interface between research and clinical development: Regulatory aspects.

During the last years, progress has been made in survival and function of pig-to-non-human primate organ xenotransplantation using organs from genetically modified pigs and immunosuppression regimens that are clinically acceptable. This, together with increased insights into a low risk of pig-to-human transmission of porcine endogenous retrovirus, has opened the perspective of starting with first-in-human trials with xenogeneic organs. The regulatory path to clinical development is complex. Unlike an organ from human donors, an organ from pigs, either genetically modified or wild-type pigs, is considered a medicinal product for human use and hence is under regulatory oversight, in the United States by the Food and Drug Administration and in Europe by the national competent authorities of the member states as well as the European Medicines Agency. Related to the status of medicinal product, "(current) good practices" apply in the process of generating a xenogeneic organ through to the transplantation into a patient and life-long follow-up. In addition, guidances for xenotransplantation products and genetically modified organisms do apply as well. This commentary focuses on regulatory aspects of transplantation of organs from genetically modified pigs into humans, with the intention to facilitate the interactions between regulatory agencies and institutions (sponsors) in research and clinical development of these organs, to support the perspective of speeding up the process with a proper entry in clinical application, to fill an unmet medical need in patients with end-stage organ disease.

CircLARP4 Suppresses Cell Proliferation, Invasion and Glycolysis and Promotes Apoptosis in Non-Small Cell Lung Cancer by Targeting miR-135b.

BackgroundCircLARP4 is reported to act as a tumor suppressor in some cancers. However, the detailed roles and molecular basis of circLARP4 in non-small cell lung cancer (NSCLC) tumorigenesis are still unclear. The aim of the study is to explore the potential roles and molecular basis of circLARP4 in NSCLC tumorigenesis.Materials and MethodsqRT-PCR was taken to detect circLARP4 and miR-135b expressions. MTT assay, transwell invasion assay and flow cytometry analysis were applied to evaluate cell proliferation, invasion and apoptosis, respectively. Glycolysis was assessed by measuring hexokinase2 (HK2) expression, glucose consumption and lactate production. Association between circLARP4 and miR-135a was examined by luciferase reporter and RIP assays. The changes of the phosphatase and tension homolog (PTEN)/protein kinase B (AKT)/hypoxia-inducible factor-1α (HIF-1α) pathway were evaluated by Western blot. The nude mouse xenograft models were applied to verify the regulation of circLARP4 in vivo.ResultsCircLARP4 was decreased in NSCLC tissues and cells. CircLARP4 overexpression blocked cell proliferation and invasion, and facilitated apoptosis in NSCLC cells. Meanwhile, circLARP4 overexpression suppressed glycolysis in NSCLC cells, as evidenced by the reduced HK2, glucose consumption and lactate production levels. Further analyses proved a downregulation of miR-135b by circLARP4 in a ceRNA-dependent manner in NSCLC cells. CircLARP4-mediated tumor suppression on NSCLC progression was partially overturned by overexpressing miR-135b. Moreover, we confirmed that circLARP4 had antitumor effect on xenograft tumors and downregulated miR-135b. Furthermore, circLARP4 overexpression inhibited the PTEN/AKT/HIF-1α pathway in NSCLC cells and xenograft tumors by downregulating miR-135b.ConclusionOur findings suggested that circLARP4 suppressed NSCLC progression by sponging miR-135b through inactivation of the PTEN/AKT/HIF-1α pathway, which broadens our understanding concerning the roles of circLARP4 in NSCLC tumorigenesis.

Development of 177Lu-EB-RGD molecular probe and its imaging and therapy in the patient-derived xenografts of non-small cell lung cancer

Objective To develop a novel αvβ3-targeted theranostic agent 177Lu-Evans blue (EB)-Arg-Gly-Asp (RGD) and evaluate its value for SPECT imaging and targeted radionuclide therapy in the non-small cell lung cancer (NSCLC)-patient-derived xenografts (PDX). Methods The αvβ3-targeted molecule RGD was conjugated with the albumin binding moiety EB to obtain EB-RGD, and EB-RGD was further conjugated with the chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) for 177Lu radiolabeling. NSCLC-PDX mice models (n=68) were established. 177Lu-EB-RGD SPECT imaging, biodistribution study were performed in 28 PDX mice models after being injected with 177Lu-EB-RGD or 177Lu-RGD. Targeted radionuclide therapy were subsequently performed in NSCLC-PDX mice models, saline group (group A), 18.5 MBq 177Lu-RGD group (group B), 18.5 MBq 177Lu-EB-RGD group (group C), 29.6 MBq 177Lu-EB-RGD group (group D), n=10 in each group; tumor volumes of PDX mice models in each group were observed within 50 d. Differences between 2 groups were compared using independent-sample t test. Results 177Lu-EB-RGD was radiolabeled at a specific activity of (55±14) GBq/μmol, with a radiochemical yield of more than 95% and a radiochemical purity of more than 95%. Regarding the SPECT imaging, tumors in NSCLC-PDX mice were clearly observed from 4 to 96 h post-injection and the tumor to muscle ratio (T/M) reached 7.34±0.67, 14.63±3.82, 15.69±3.58 and 15.99±5.42 at 4, 24, 72, 96 h post-injection, respectively. Biodistribution study further confirmed the findings from SPECT imaging, and the tumor uptake of 177Lu-EB-RGD were markedly increased compared to 177Lu-RGD 4 h post-injection ((10.15±1.17) vs (3.30±1.47) percent injection dose per gram (%ID/g); t=18.60, P<0.05). Regarding targeted radiotherapy, the tumor volumes were quickly increased within 50 d after treatment in group A and B, while the tumor volumes were decreased in group C and D, until the tumors in group C and D disappeared at the 28th day after initial treatment with no sign of recurrence during the observation period. Conclusions 177Lu-EB-RGD can target αvβ3-positive NSCLC-PDX with intense tumor to background ratio and strong tumor inhibition efficacy. The preclinical data suggests that 177Lu-EB-RGD may be an effective new treatment option for advanced NSCLC patients with resistance or ineffective results for targeted therapy. Key words: Carcinoma, non-small-cell lung; Xenograft model antitumor assays; Evans blue; Arginine-glycine-aspartic acid; Lutetium; Mice, nude

Sensitive detection systems for infectious agents in xenotransplantation.

Xenotransplantation of pig cells, tissues, or organs may be associated with transmission of porcine microorganisms, first of all of viruses, to the transplant recipient, potentially inducing a disease (zoonosis). I would like to define detection systems as the complex of sample generation, sample preparation, sample origin, time of sampling, and the necessary negative and positive controls along with the specific detection methods, either PCR-based, cell-based, or immunological methods. Some xenotransplantation-relevant viruses have already been defined; others are still unknown. The PCR-based methods include PCR and real-time PCR for DNA viruses, and RT-PCR and real-time RT-PCR for RNA viruses as well as for virus expression studies at the RNA level. Furthermore, droplet digital PCR (ddPCR) can be used for the determination of virus and provirus copies. To detect expression at the protein level, immunofluorescence, immunohistochemistry, and Western blot analyses can be used. To detect virus production and to detect infectious viruses, electron microscopy and infection assays can be used. Furthermore, immunological methods such as Western blot analysis or ELISA can be used to detect virus-specific antibodies. Detection of antiviral antibodies is a reliable and sensitive indirect detection method. For these immunological methods, purified viruses, recombinant viral proteins, or synthetic peptides are used as antigens and control sera and control antigens are needed. All these methods have been used in the past for the characterization of different pig breeds including genetically modified pigs generated for xenotransplantation and for the screening of recipients in preclinical and clinical xenotransplantations. Whereas in preclinical trials a few porcine viruses have been transmitted to the non-human primate recipients, in first clinical trials no such transmissions to humans were observed. Further improvement of the detection systems and their application in virus elimination programs will lead to clean donor animals and a safe xenotransplantation.

Peptide specifically binding to human medullary breast carcinoma Bcap-37 cells selected by phage display in vivo and its property as well as combination effect

Objective To investigate the property and the combination effect of the peptide specifically binding to human medullary breast cancer Bcap-37 cells by using phage display in vivo and to provide molecular targeting probe for early diagnosis of breast cancer. Methods The human medullary breast carcinoma Bcap-37 cells tumor-bearing nude mice model was prepared and three rounds in vivo were performed by using Ph.D.-C7CTM phage display peptide library. The distribution of screened phages in tumors and normal tissues was detected by using immunohistochemistry. The affinity of monoclonal phage to Bcap-37 cells was identified by using enzyme linked immunosorbent assay (ELISA). The positive monoclonal phage DNA was taken and sequenced, and the sequence with high repetition rate was selected to synthesize peptide by using chemical methods. Optical molecular probe was prepared and fluorescence molecular imaging was used to test its specificity and targeting ability for breast transplantation tumor of tumor-bearing nude mice in vivo. Results The recovery rate of phage in the third round screening in vivo was 107.2 times than that in the first round. Immunohistochemical results showed that the phages binding to the tumor tissues were increased successively with the increasing screening rounds in vivo. The number of phages binding to tumor tissues was more than that binding to normal tissues (lung, skeletal muscle, liver and kidney). The absorbancy (A) value of section scanning image in the tumor tissues was higher than that in the normal tissues, and the difference was statistically significant different (P < 0.05). ELISA results showed that 22 phages (affinity≥2) among the 50 randomly selected monoclonal phage were positive. After DNA sequencing analysis of the positive monoclonal phage, 4 repeat amino acid sequences were obtained. The fluorescein isothiocyanate-labelled (FITC)-CSPLNTRFC with the highest repetition rate was synthesized for FITC-CSPLNTRFC peptide. Bcap-37 cells tumor-bearing nude mice model assay in vivo showed that FITC-CSPLNTRFC peptide could significantly enriched in the breast xenograft tissues. Conclusion CSPLNTRFC peptide specifically binding to human medullary breast cancer Bcap-37 cells can be screened out successfully by using phage display in vivo, which will be helpful to vitro studies on the early diagnosis of breast cancer. Key words: Breast neoplasms; Peptide library; Phage display; Specifically binding peptide

Are Medical Students of Non-Spanish Nationality Studying in Spain as Sensitized to Transplantation as Those of Spanish Nationality?

IntroductionAwareness of organ donation among Spanish doctors and medical students is very positive. However, the emerging group of professionals of non-Spanish nationality studying in Spain has not been analyzed. ObjectiveTo analyze the differences in the attitudes toward the different types of donation among medical students, according to their nationality. MethodsThe population under study is medical students in Spanish universities using the database of the International Collaborative Donor Project, stratified by geographic area and academic year. Groups under study include students of non-Spanish nationality as group 1 (n = 1570) and students of Spanish nationality as Group 2 (n = 7705). Instruments are validated questionnaires of attitude toward donation “PCID-DTO-Ríos,” “PCID-DVR-Ríos,” “PCID-DVH-Ríos,” and “PCID-XenoTx-Ríos.” ResultsThe attitude toward the donation of own organs after death is similar in both groups (P = .703). Non-Spaniards are 79.2% in favor compared to 79.6% of Spaniards. Living kidney donation, both unrelated (33.3% vs 29.3% in favor; P = .001) and related (91.2% vs 89, 6% in favor; P = .047), is more favorable among non-Spanish students. There are no differences regarding non-related living liver donation (29.7% vs 29.3% in favor; P = .063), but there are differences in the results for related living liver donation (94.1% vs 88%; P < .001). The attitude toward xenotransplantation of organs is similar (80.8% vs 80.8%; P = .999). ConclusionsAwareness of the donation of organs among Spanish medical students is similar to non-Spanish students studying in Spain, except the attitude toward living donation.

Population of Senegal Residents in Spain: Acceptance of Organ Xenotransplantation

IntroductionSpain is a great receptor of immigration from sub-Saharan people like the Senegalese. This population is not very familiar with the process of organ donation and transplantation, and even less toward new therapies related to transplantation, such as xenotransplantation (XenoTx). ObjectiveAnalyze the attitude toward XenoTx among the Senegalese population living in Spain. Material and MethodsPopulation under study. Population born in Senegal and resident in Spain. Inclusion criteria. Sample of population over 15 years stratified by age and sex, according to census data and immigrant assistance associations. Instrument. Validated questionnaire of attitude toward donation and organ transplantation “PCID-XenoTx-Ríos.” Field work. Random selection of respondents based on stratification. The support of immigration support associations was required to obtain sample locations. The completion was anonymous and self-administered. ResultsA sample of 468 Senegalese was obtained. Twenty percent (n = 92) would accept a solid organ xenotransplant if the results were similar to human organs, 40% (n = 188) have doubts, and 40% (n = 188) would not accept it. If the results were worse than with human organs, only 8% would accept it (n = 38). Respondents with a favorable attitude toward XenoTx presented a more favorable attitude toward cadaveric donation (70.5% vs 31.3%; P < .001).The attitude toward acceptance of XenoTx is related to socio-personal factors (P < .05), knowledge about the process of organ donation and transplantation (P < .05), social interaction factors (P < .001), and religious factors (P < .05). ConclusionsSenegalese residing in Spain do not have a favorable attitude toward XenoTx. A direct relationship between the attitude toward XenoTx and organ donation is observed.

Is the Population of Santiago de Cuba Sensitized to Xenotransplantation? A Multivariate Analysis

IntroductionNew transplant-related therapies such as xenotransplantation of solid cells, tissues, and organs are still poorly understood, especially in countries without preclinical xenotransplantation programs. ObjectiveAnalyze the attitude toward xenotransplantation among the population of Santiago de Cuba. MethodType of study. Cross-sectional observational study. Sample. Random sampling of 455 individuals residing in Santiago de Cuba. Assessment instrument. Validated questionnaire of attitude toward the xenotransplant, “PCID-XenoTx-Ríos.” Field work. Random selection based on stratification. Anonymous and self-administered completion. ResultsA total of 49.9% would accept a solid organ xenotransplant if they needed it and the results were similar to those currently obtained with human organs, 27.5% have doubts, and the remaining 22.6% would not accept it. They are presented as statistically significant variables (P < .05): level of studies; comment with the family about the donation; opinion of a partner; religion; opinion of religion; performing prosocial activities; attitude toward donation; previous relationship with the organ donation and transplant; favorable attitude toward live kidney donation. In the multivariate analysis, the following persist: 1. level of university studies: odds ratio (OR) = 5.076; 2. not having a partner: OR = 5.154; 3. belonging to another religion: OR = 2.061; 4. favorable attitude toward organ donation: OR = 5; and 5. favorable attitude toward living donation: OR = 3.759. ConclusionsThe population of Santiago de Cuba is less sensitized toward xenotransplantation, possibly due to ignorance of the issue due to lack of preclinical trials in their countries.

Nicaraguan Population Residing in Florida Attitude Toward Different Types of Organ Donation

IntroductionThe population of Nicaraguan immigrants is growing in North America; however, they have been little analyzed concerning their attitude toward donation and organ transplantation. ObjectiveTo analyze the attitude toward the different types of organ donation among the Nicaraguan population residing in Florida. MethodsStudy population. Nicaraguan population residing in Florida (USA). Inclusion criteria. Population sample over 15 years stratified by age and sex. Instrument valuation. Attitude questionnaires toward organ donation for transplantation “PCID-DTO-Ríos,” “PCID–DVR-Ríos,” and “PCID–XenoTx-Ríos.” Setting for the study. Random selection of people to be surveyed according to stratification. The assistance of immigrant support associations in Florida was required to locate respondents. ResultsSample composed of 89 participants. In the attitude toward donation of one’s own organs after death, 22% (n = 20) were in favor, 41% (n = 36) were against, and 37% (n = 33) were undecided. Regarding the donation of living related organs, 76% were in favor (n = 68), 10% were against (n = 9), and 14% were undecided (n = 12). Finally, regarding attitudes toward the acceptance of organ xenotransplantation, if the results were similar to those obtained with human organs, they were not in favor, with 72% (n = 64) against and 28% (n = 25) doubtful. ConclusionsThe attitude of the Nicaraguan population residing in Florida toward different types of organ donation is unfavorable.

Acceptance of Solid Organ Xenotransplantation by the Ecuadorian Population Residing in Spain

IntroductionEcuadorians are the largest immigrant group in Spain. In countries with preclinical programs of xenotransplantation (XenoTx), it is important to know the population attitude toward them; however, in the Ecuadorian population it is not known. ObjectiveTo analyze the attitude toward XenoTx of organs among the Ecuadorian population residing in Spain. MethodsPopulation under study. Ecuadorians residing in Spain. Inclusion criteria: Sample of population over 15 years stratified by age and sex. Instrument valuation. Validated questionnaire of attitude towards xenotransplantation PCID-XenoTx-Ríos. Setting for the study. Random selection of people to survey based on stratification. ResultsOf the 461 respondents, 36% are in favor of XenoTx if the results were similar to those obtained with humans, 15% against, and 49% undecided. If the results were worse than with human organs, 11% would be in favor, 26% against, and 63% undecided. The variables associated with this attitude are age (P = .018), marital status (P = .026), studies (P < .001), comment with family (P = .001), couple attitude (P = .039), attitude toward cadaveric donation (P < .001), previous experience with donation (P = .001), consider the possibility of needing a transplant in the future (P < .001), and attitude toward related living donation (P < .001). In the multivariate analysis, these data persist: university studies (odds ratio [OR] = 3.875; P = .007); in favor of cadaveric organ donation (OR = 2.840; P < .001); previous relationship with donation and organ transplantation (OR = 1.901; P = .026); and consider the possibility of needing a transplant in the future (OR = 4.329; P = .002). ConclusionsThe attitude toward XenoTx among Ecuadorian residents in Spain is unfavorable and is conditioned by different psychosocial variables.

Effects of Human Amniotic Mesenchymal Stem Cells on Acute Graft-Versus-Host Disease in Xenotransplantation

To investigate the effects of human amniotic mesenchymal stem cell（AMSC） on acute graft-versus-host disease (aGVHD) in xenotransplatation. NPG mice were injected with human PBMNC via tail vein to establish a xenografted aGVHD model. The mice in the experimental group were divided into PBMNC infusion group and PBMNC+AMSC co-infusion group, the general condition, survival time and manifestations of aGVHD were observed, the body weight and blood routine indicators were detected, the pathological changes of aGVHD target organs (lung, liver, spleen, small intestine) were observed by HE staining, and the levels of human T cells in peripheral blood, tissues and organs of mice was detected by flow cytometry. The manifestations of aGVHD (lassitude hunchback, shrub, weight reduction, etc.) and the pathological damage of the target organs (lung, liver, spleen, intestine) in PBMNC+AMSC co-infusion group were lighter than those in PBMNC infusion group. Moreover, the PBMNC and AMSC co-infusion significantly reduced the implantion proportion of human T lymphocytes (CD3+, CD45+) in mice and increased the ratio of CD4+/CD8+. Infusion of human-derived AMSC can attenuate the manifestations of aGVHD in mouse xenografts to a certain level, and improve the pathological damage of receptor target organs.