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PubMed2003

Effect of recombinant human deoxyribonuclease on the expression of cell adhesion molecules of thawed and processed cord blood hematopoietic progenitors.

BACKGROUND AND OBJECTIVES: The integrity of granulocytic cells and platelets is compromised within cryopreserved stem cell transplants, and consequent DNA release during the thawing procedure can therefore lead to clotting phenomena or microaggregate formation and that in turn may cause loss of progenitor cells. To circumvent this problem a new processing protocol was introduced using recombinant human deoxyribonuclease (rhDNase) to prevent cell aggregate formation. In addition, the impact of this new processing protocol on CD34+ umbilical cord blood (UCB) cells was assessed. MATERIALS AND METHODS: Fifty samples derived from 7 buffy coat (BC) volume reduced UCB units were cryopreserved, thawed, and processed with washing solutions that were supplemented with rhDNase in various concentrations. Thereafter, clotting and microaggregate formation was scored microscopically. In addition, expression of the adhesion molecules leukocyte function-associated antigen 1 (LFA-1, n = 6), intercellular adhesion molecule-1 (ICAM-1, n = 11), and L-selectin (n = 11) on CD34+ UCB cells was analyzed by flow cytometry after incubating the samples with either dimethyl sulfoxide (DMSO) 5.5%, rhDNase 10 or 50 U/mL, or a combination of DMSO 5.5% and rhDNase 50 U/mL. RESULTS: At a minimal concentration of 10 U rhDNase/mL, clotting or microaggregate formation could be prevented for all tested samples, whereas cell clots could be observed for concentrations up to 8 U/mL. The expression of adhesion molecules on untreated CD34+ UCB cells (L-selectin: 64.6 +/- 18.8%; LFA-1: 62.6 +/- 7.5%; ICAM-1: 14.8 +/- 4.1%) did not show any significant difference compared with cells that were incubated with up to 50 U/mL rhDNase (L-selectin: 62.2 +/- 19.3%; LFA-1: 63.1 +/- 5.9%; ICAM-1: 17.5 +/- 6.7%). However, after a combined treatment with DMSO 5.5% and rhDNase 50 U/mL, a slight but significant decrease in L-selectin expression could be observed (P < 0.03). CONCLUSION: The supplementation of rhDNase to a final concentration of 10 U/mL cell suspension proved to be effective in preventing clot formation under the conditions examined and did not lead to decreased expression levels of adhesion molecules. We therefore recommend the use of rhDNase for the prevention of clot formation and cell loss during the processing of thawed UCB transplants.

Antigens, CD34↗

PubMedDate not supplied

Human sperm cryopreservation and reactive oxygen species (ROS) production.

The aim of this work was to establish whether cryopreservation procedure can trigger the production of Reactive Oxygen Species (ROS) in selected sperm populations. Semen samples were obtained from 45 subjects attending our Department of Medical Pathophysiology. Motile sperm suspensions were obtained by swim-up in Tyrode's salt solution. After dilution with TEST yolk buffer freezing medium, they were cryopreserved in liquid nitrogen. In addition to motility assessment, in basal and freeze/thaw conditions ROS detection and the Hypoosmotic Viability Test were also carried out. In 19 subjects (42.2%) there was already evidence of ROS production prior to cryopreservation, which increased after thawing. In 9 subjects (20.0%) there was no ROS production prior to cryopreservation, however, after freezing/thawing we detected evidence of the presence of ROS. It seems, therefore, that cryoprocedure can indeed provoke or increase ROS production in some semen samples. In ROS producing subjects, the post-show recovery of sperm motility and vitality was significantly lower compared to ROS-free subjects. This was probably due to damage by oxidative stress leading to lipid peroxidation of the sperm membrane. Moreover, in some ejaculates, ROS overproduction or scavenger system failure can be regarded as a cryopathogenetic factor affecting "sperm quality" recovery.

Adult↗

PubMed2000

Assessment of sperm cryodamage and strategies to improve outcome.

Sperm cryopreservation still represents a valuable clinical aid in the management of infertility. Its current principal indications include (1) donor sperm insemination; (2) freezing before cancer therapy to maintain reproductive capacity; (3) patient's convenience; and (4) because of the outstanding success with ICSI, even patients with different degrees of oligo-asthenoteratozoospermia can now be offered the use of frozen/thawed sperm for oocyte micromanipulation. Although sperm cryopreservation/thawing and results of insemination and IVF have been consistently good using donor semen, results of infertile men (with or without various degrees of oligoasthenoteratozoospermia) have yielded remarkably lower rates of survival and pregnancy. Freezing/thawing techniques have not been subjected to major changes in the last years, Furthermore, the exact nature of sperm cryodamage still remains to be elucidated. Various aspects of sperm freezing are revisited here (1) development of new technical approaches for cryopreservation; (2) analysis of the stimulatory effect of putative cryoprotectant additives; (3) the use of intrauterine insemination-ready processed samples; and (4) selection and optimization of end-points for analysis of cryodamage. It is expected that advances in such areas will improve significantly the cryopreservation/thawing outcome particularly as related to semen samples of subfertile men.

Cryopreservation↗

PubMed2001

Translational extracts active biologically in vitro obtained from eukaryotic monolayer cells: a versatile method for viral RNA studies.

Preservation of enzymatic activities in biological samples, especially after freeze/thawing, is a crucial requirement in virological research. Theoretically, this preservation can be achieved with the presence of cryopreservative agents. In contrast to tedious methods, it was found that this might be readily achieved by using well-defined conditions, including sucrose in the samples. Hence, the generation of a translational extract obtained from eukaryotic cells that have grown as monolayers is described below. This versatile method could be used advantageously for the in vitro translation of messenger RNAs, added exogenously, including viral mRNAs. The translational extract can be prepared freshly on a daily basis, or more conveniently it can be frozen and thawed subsequently for further use, without loss of activity. It can replace the Krebs ascites fluid and the commercial rabbit reticulocyte lysate. The procedure employed for the preservation of the biological activity of the translational extract can be extended to various other biological samples.

Animals↗

PubMed1997

Evaluating sex chromosome content of sorted human sperm samples with use of dual-color fluorescence in situ hybridization.

OBJECTIVE: Although most methods for selecting the sex of offspring by sorting spermatozoa are ineffective at shifting the ratio of Y- to X-containing cells, some commercial sources continue to offer such services. Our objective was to evaluate commercially "sorted" samples with use of dual-color fluorescence in situ hybridization and to identify variations in assessment by comparing motile and total sperm populations, donors, observers, and fluorescence in situ hybridization probes. STUDY DESIGN: Cryopreserved sperm from seven anonymous donors were processed as for insemination. Sperm cells from each total sample or motile subfraction were prepared for fluorescence in situ hybridization by incubation with disulfide-reducing agents to expand sperm nuclei. Two sets of X and Y chromosome-specific, fluorophore-labeled deoxyribonucleic acid probes were used. At least 400 nuclei from each preparation were classified independently by three blinded observers. Hybridization efficiency, aneuploidy, and sex chromosome content were evaluated in subsets of five unsorted, five female-oriented, and five male-oriented samples. Total and motile subfractions were compared with eight samples. Fluorescence in situ hybridization probes were compared in five paired unsorted samples. RESULTS: No differences were detected between washed samples and paired motile subfractions. No differences in hybridization and aneuploidy were detected between groups of sorted samples. The Y/X ratio was significantly different between the sorted groups. However, male-oriented samples had a lower Y/X ratio than female-oriented samples did. Observer and probe choice accounted for small but significant variations that did not alter conclusions about the X/Y ratio for sorted samples. CONCLUSION: In a series of 10 sorted samples from one commercial source, dual-color fluorescence in situ hybridization demonstrated a small but significant shift in the sex chromosome ratios among samples. However, this shift was opposite to that expected by the orientation of the sorted samples.

Analysis of Variance↗

PubMed1998

Effect of shipment, storage, anticoagulant, and cell separation on lymphocyte proliferation assays for human immunodeficiency virus-infected patients.

Lymphocyte proliferation assays (LPA), which can provide important information regarding the immune reconstitution of human immunodeficiency virus (HIV)-infected patients on highly active antiretroviral therapy, frequently involve shipment of specimens to central laboratories. In this study, we examine the effect of stimulant, anticoagulant, cell separation, storage, and transportation on LPA results. LPA responses of whole blood and separated peripheral blood mononuclear cells (PBMC) to different stimulants (cytomegalovirus, varicella-zoster virus, candida and tetanus toxoid antigens, and phytohemagglutinin) were measured using fresh specimens shipped overnight and frozen specimens collected in heparin, acid citrate dextrose (ACD), and citrate cell preparation tubes (CPT) from 12 HIV-infected patients and uninfected controls. Odds ratios for positive LPA responses were significantly higher in separated PBMC than in whole blood from ACD- and heparin-anticoagulated samples obtained from HIV-infected patients and from ACD-anticoagulated samples from uninfected controls. On separated PBMC, positive responses were significantly more frequent in fresh samples compared with overnight transportation for all antigens and compared with cryopreservation for the candida and tetanus antigens. In addition, viral antigen LPA responses were better preserved in frozen PBMC compared with specimens shipped overnight. CPT tubes yielded significantly more positive LPA results for all antigens, irrespective of the HIV patient status compared with ACD, but only for the candida and tetanus antigens and only in HIV-negative controls compared with heparin. Although HIV-infected patients had a significantly lower number of positive antigen-driven LPA responses compared with uninfected controls, most of the specimen processing variables had similar effects on HIV-positive and -negative samples. We conclude that LPA should be performed on site, whenever feasible, by using separated PBMC from fresh blood samples collected in either heparin or ACD. However, if on-site testing is not available, optimal transportation conditions should be established for specific antigens.

Adult↗

PubMed2005

The origin, ultrastructure, and microbiology of the sediment accumulating in liquid nitrogen storage vessels.

During long-term cryopreservation, ice sediment accumulates in storage Dewars and poses a risk of microbial contamination to stored samples. Ice accumulates in liquid nitrogen via two general processes: (1) ice forming in the atmosphere above an open Dewar falls into the vessel; and (2) ice forming on cold surfaces of the Dewar or inventory system enters the liquid nitrogen. These ice crystals aggregate and entrap other materials, such as bacteria, fungal spores, and general laboratory debris present within the liquid nitrogen. Measured changes in the ultrastructure of ice aggregates following long-term storage are consistent with transient warming events to temperatures of -100 degrees C. Bacteria were identified in all samples and filamentous fungi in 9 out of 10 samples. These micro-organisms are commonly found in the environment and would not be expected to have been derived from IVF samples. Some of the bacteria identified are associated with nosocomial infections in humans. The implications that the association of microbial contamination with ice crystals has on cryopreservation procedures are discussed.

Animals↗

PubMed2005

Cryopreservation of intact testicular tissue from boys with cryptorchidism.

BACKGROUND: Boys with cryptorchidism often face fertility problems in adult life despite having orchiopexy performed at a very young age. During this operation, a biopsy of the testis is normally taken in order to evaluate their infertility potential and the presence of malignant cells. This study evaluated the morphology and functional capacity of cryopreserved testes biopsies and their possible use in fertility preservation. METHODS: Biopsies from 11 testes (eight boys) were obtained. Each biopsy was subdivided into six pieces and two pieces were frozen in each of two different cryoprotectants. One fresh and two cryopreserved pieces were cultured for 2 weeks. All pieces were prepared for histology. Used culture media were analysed for testosterone and inhibin B concentrations. RESULTS: The morphology of the fresh and frozen-thawed samples was similar, with well-preserved seminiferous tubules and interstitial cells. A similar picture appeared after 2 weeks of culture, but a few of the cultured biopsies contained small necrotic areas. The presence of spermatogonia was verified by c-kit-positive immunostaining. Production of testosterone and inhibin B (ng/mm(3) testis tissue) in the frozen-thawed pieces was on average similar to that of the fresh samples. CONCLUSIONS: Intact testicular tissue from young boys with non-descended testes tolerates cryopreservation with surviving spermatogonia and without significant loss of the ability to produce testis-specific hormones in vitro. It may be an option to freeze part of the testis biopsy, which is routinely removed during the operation for cryptorchidism, for fertility preservation in adult life.

Biopsy↗

PubMed2000

Detection of Gov system antibodies by MAIPA reveals an immunogenicity similar to the HPA-5 alloantigens.

The glycosylphosphatidylinositol-linked platelet protein CD109 carries the biallelic alloantigen system Gov. There is limited information on the incidence of Gov alloantibodies in neonatal alloimmune thrombocytopenia (NAITP), post-transfusion purpura (PTP) and platelet refractoriness. We adapted the monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay to the detection of Gov antibodies and determined their incidence in 605 archived samples (112 with HPA antibodies) referred for the aforementioned conditions. Here, we show that CD109 expression was reduced upon platelet storage in saline or by cryopreservation, but was stable when stored as whole blood or therapeutic platelet concentrate. Fourteen of the 605 samples contained Gov alloantibodies (anti-Gova, n = 10; anti-Govb, n = 4), with the majority in platelet refractoriness (n = 9) and, of the remaining five, four in NAITP and one in PTP. In seven cases, no other HPA antibodies were detected, three being NAITP cases. The incidence of Gov antibodies was significantly lower than HPA-1 system antibodies (n = 87), but equalled the number of HPA-5 system antibodies (n = 14) and outnumbered HPA-2 and -3 system antibodies (10 altogether).

Alleles↗

PubMed2002

Enhanced culture method for detection of replication-competent virus in peripheral blood mononuclear cells of HIV type 1-infected individuals.

The detection of replication-competent human immunodeficiency virus type 1 (HIV-1) in infected individuals is integral for studies of viral latency and reservoirs of continuing replication during treatment. We describe a modified coculture method to detect/isolate virus from HIV-1-infected individuals with low or undetectable plasma viral loads. We observed a wide range in CD4 and chemokine receptor concentrations on CD4(+) T cells of HIV-1-uninfected donors. We selected cells from donors who expressed high levels of CCR5 after mitogen stimulation to combine in culture with peripheral blood mononuclear cells of HIV-1-infected individuals. Using this donor-enhanced culture method, viruses were isolated from asymptomatic adults with longterm nonprogressive infection, and children receiving effective highly active antiretroviral therapy, whereas parallel cultures with cells expressing lower levels of CCR5 yielded none. Virus was isolated from an individual for whom all previous attempts using reported methods were unsuccessful. Virus growth from cryopreserved cells from this same individual was detected at multiple sampling time points, including a time point at which a sensitive assay to measure 2-LTR (long terminal repeat) circular forms of the viral genome was negative. This will be a useful technique by which to study viral latency and HIV-1 pathogenesis in adult and pediatric populations.

Adult↗

PubMedDate not supplied

Measurement of transmitted light as an indicator of cryopreserved platelet viability.

This study was designed to establish an alternative technique to the morphology scoring method described by Kunicki et al. [Transfusion 1975;15:414-421] using light transmission. A reference scale for platelet quality (expressed as a percentage of fresh cells) was established with a mixture of fresh platelets and damaged platelets frozen without cryoprotectant. The transmittance, read against autologous plasma, was compared to morphology, hypotonic stress response (HSR) and ADP-induced aggregation. The results showed that transmittance, morphology and HSR were related linearly to the percentage of fresh platelets. There was a significant correlation between relative transmittance (RT) and morphology (r = 0.932), and RT and HSR (r = 0.91), but a very poor correlation was found between transmittance and aggregation. Measurements of transmittance provided an estimation of the global aspect of a population of cryopreserved platelets in terms of shape, size and composition, and the relative transmittance of a sample to that of the fresh population could predict morphology and HSR. It is concluded that these measurements offer a valid alternative method to the subjective morphology scoring obtained with cryopreserved platelets.

Adenosine Diphosphate↗

PubMed2001

Telomerase activity in Kaposi's sarcoma, squamous cell carcinoma, and basal cell carcinoma.

Patients with acquired immune deficiency syndrome (AIDS) often develop Kaposi's sarcoma (KS), an unusual skin tumor. The malignant nature of KS has long been disputed. Telomerase activity that maintains telomere length and ensures chromosomal stability, a frequently appearing marker in human malignancies, has been proposed to play a critical role in supporting continued cell growth, hence formation of tumors. We examined telomerase activity in tissue extracts from 22 KS, 10 squamous cell carcinoma (SCC), and 22 basal cell carcinoma (BCC) using the telomeric repeat amplification protocol (TRAP). All of the tumor tissues were previously cryopreserved at -80 degrees C. In this study, all tumor samples tested were positive for telomerase activity. Consistent with the presence of the enzyme activity, the skin tumors had relatively long telomeres. Inhibitors in the tissue extracts of some samples needed to be diluted or extracted by phenol before the enzyme activity was detected in the TRAP assay. All KS as well as two other skin carcinoma samples revealed positive telomerase activity. Our finding supports telomerase's role in tumor cell immortality and suggests the true neoplastic nature of KS.

Adult↗

PubMed1987

Proteins in stallion seminal plasma.

Motility and fertility of frozen-thawed semen differs greatly amongst stallions. Differences in seminal plasma might be one cause of this variation. For 8 ejaculates from each of 17 stallions, seminal plasma was saved at -20 degrees C and spermatozoa were cryopreserved. Based on post-thaw sperm motility, seminal plasma samples from 7 stallions (2 good, 3 variable, 2 poor sperm motility) were selected for measurement of electrolytes, protein content and analysis by sodium dodecylsulphate gel electrophoresis (10% gel, Coomassie blue stain). Variation in seminal plasma was significant (P less than 0.05) amongst stallions for concentrations of Na, K, Ca and Cl, but not for P or protein. A total of 27 proteins, of 13,000 to 122,000 molecular weight, were detected in seminal plasma. There was a difference (P less than 0.05) amongst stallions in the proportion of ejaculates containing 13 of the 27 proteins. However, only for Proteins 23 and 26 was there a significant correlation between the relative amount of protein and sperm motility (0, 30 or 60 min after thawing; r = 0.42-0.50). These correlation coefficients, or those with concentration of K, were too low to be of predictive value. Therefore, although an effect of a minor protein can not be excluded, variation in the relative amounts of major proteins in seminal plasma probably is not a cause of differences in post-thaw motility of stallion spermatozoa.

Animals↗

PubMed2003

Detection of antigen-specific T cell interferon gamma expression by ELISPOT and cytokine flow cytometry assays in rhesus macaques.

Both enzyme-linked immunospot (ELISPOT) and cytokine flow cytometry (CFC) methods have been developed for the detection of low-frequency, antigen-specific, cytokine-producing T cells following short-term in vitro stimulation. Peptide-based ELISPOT and CFC assays were compared for the quantitative detection of interferon gamma-positive (IFN-gamma+) antigen-specific T cells in rhesus macaques. Ten normal and nine simian immunodeficiency virus (SIV)-infected monkeys were tested for the detection of IFN-gamma+ memory T cells specific for p27(gag) peptides of SIV with both assays. The CFC assay detected more IFN-gamma+ cells than the ELISPOT assay and this assay was more informative in identifying the phenotype of responding cells. Cryopreserved cells were as functional as fresh cells in heparinized blood samples and compared to EDTA, heparin was the better anticoagulant for yielding IFN-gamma+ cells. Using overlapping peptide pools, 20-mer peptides were more efficient in stimulating CD4+ T cells than 15-mer peptides in the ELISPOT assay, but there was no significant difference between 20- and 15-mer peptides in detecting CD4 or CD8+, IFN-gamma+ T cells in the CFC assay.

Animals↗

PubMed1987

Activity of platelet-derived growth factor (PDGF) in platelet concentrates and cryopreserved platelets determined by PDGF bioassay.

The bioassay of platelet-derived growth factor (PDGF) in platelets was established using the rat fibroblast cell line 3Y1. 3Y1 cells (5 X 10(3)/well) were cultured in 24-well microculture plates with RPMI 1640 medium using 1% of PDGF-free serum and 5% of platelet extracts for 4 days. Cell proliferation was measured by the increase of DNA content. This assay made it possible to measure the biological PDGF activity. PDGF activity of platelet concentrates kept the same level as that of fresh platelet samples during preservation for up to 120 h at 22 degrees C; cryopreserved platelets also retained PDGF activity well.

Biological Assay↗

PubMed1992

Changes in carnitine and acetylcarnitine in human semen during cryopreservation.

L-Carnitine and acetylcarnitine concentrations were determined in spermatozoa and seminal plasma from 15 men, in both fresh ejaculate and frozen-thawed semen with cryoprotective medium. Sperm motility was also evaluated. In fresh samples, the levels of carnitine and acetylcarnitine in seminal plasma were comparable whereas in spermatozoa, acetylcarnitine predominated. Cryopreservation did not change the carnitine and acetylcarnitine levels in seminal plasma nor the carnitine concentration in spermatozoa; by contrast, the acetylcarnitine level in spermatozoa was decreased in 14 cases (110 +/- 8 versus 210 +/- 20 nmol/10(8) cells). This decrease in acetylcarnitine content was greater during semen dilution in cryoprotectant than after the freezing/thawing process. Motility was also decreased in all cases after the freezing/thawing process. These results suggest that acetylcarnitine recovery in spermatozoa is further evidence of the deleterious effect of the cryoprotective medium in the cryopreservation of semen.

Acetylcarnitine↗

PubMed2003

Cord blood stem cell banking and transplantation.

Stem cells have the ability to divide for indefinite periods in culture and to give rise to specialized cells. Cord blood as a source of hematopoietic stem cells (HSC) has several advantages as it is easily available, involves non-invasive collection procedure and is better tolerated across the HLA barrier. Since the first cord blood transplant in 1988, over 2500 cord blood HSC transplants have been done world wide. Since then, the advantages of cord blood as a source of hematopietic stem cells for transplantation have become clear. Firstly, the proliferative capacity of HSC in cord blood is superior to that of cells in bone marrow or blood from adults. A 100 ml unit of cord blood contains 1/10th the number of nucleated cells and progenitor cells (CD34+ cells) present in 1000 ml of bone marrow, but because they proliferate rapidly, the stem cell in a single unit of cord blood can reconstitute the entire haematopoietic system. Secondly, the use of cord blood reduces the risk of graft vs host disease. Cord Blood Stem Cell banks have been established in Europe and United States to supply HSC for related and unrelated donors. Currently, more than 65,000 units are available and more than 2500 patients have received transplants of cord blood. Results in children have clearly shown that the number of nucleated cells in the infused cord blood influences the speed of recovery of neutrophils and platelets after myeloablative chemotherapy. The optimal dose is about 2 x 10(7) nucleated cells/kg of body weight. The present study was carried out for collection, separation, enumeration and cryopreservation of cord blood HSC and establishing a Cord Blood HSC Bank. 172 samples of cord blood HSC were collected after delivery of infant prior to expulsion of placenta. The average cord blood volume collected was 101.20 ml. Mononuclear cell count ranged from 7.36 to 25.6 x 10(7)/ml. Viability count of mononuclear cells was 98.1%. After 1 year of cryopreservation, the viability count on revival was over 82.1%. Related cord blood stem cell transplantation was carried out in three cases at Army Hospital (R&R), Delhi Cantt.

Blood Banking↗

PubMed2004

Cortisol does not mediate the suppressive effects of psychiatric morbidity on natural killer cell activity: a cross-sectional study of patients with early breast cancer.

BACKGROUND: There is evidence that depression impairs natural killer cell activity (NKA); this could have implications for anti-tumour immunity. Our aim was to examine the role of the hypothalamic-pituitary-adrenal (HPA) axis in suppressing NKA in a population of patients with early breast cancer, screened for depression. Secondary aims were to study the relationship between psychological, endocrine and immune variables and baseline tumour characteristics. METHOD: A cross-sectional population of female patients (n=55) with early breast cancer was sampled prior to primary surgery. Structured interview and psychometric instruments measured psychological distress. Flow cytometry was used to enumerate NK cells and lymphocytes were cryopreserved for use in a 51Cr-release assay, to estimate NKA. Midnight and three early morning saliva samples were collected to measure free cortisol levels. Tumour characteristics were obtained from hospital laboratory data. RESULTS: A high rate of psychological morbidity (40%) was observed in the population. NKA was reduced in those with past or current psychiatric illness compared to those without (344 v. 553 LU20 and 455 v. 569 LU20 respectively, p < 0.05 for both). Cortisol was not related to psychological status but was modestly positively correlated to NKA. A positive correlation was observed between the Fighting Spirit subscale of the Mental Adjustment to Cancer Scale and tumour size (r=0.383, p=0.012). CONCLUSIONS: Our data support the evidence that psychological morbidity is associated with immune dysfunction; however, the most obvious candidate mediator of this effect, the HPA axis, does not appear responsible for this effect. Possible reasons for this are discussed.

Adult↗