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PubMedDate not supplied

Hematopoietic stem cell transplantation from alternative sources in adults with high-risk acute leukemia.

Since 75% of patients with high-risk acute leukemia do not have a human leukocyte antigen (HLA)-identical sibling, alternative sources for hematopoietic stem cell transplantation (HSCT) are matched unrelated donors (MUD), unrelated umbilical cord blood (UD-UCB) and one HLA haplotype mismatched family members (haploidentical). The chance of finding a suitable donor in the international voluntary donor registries is limited by frequency of the HLA phenotype and the time required to identify the right donor from a potential panel, to establish eligibility and to harvest the cells. In adult MUD recipients, event-free survival ranges up to 50% and refers only to patients who undergo transplant, without taking into account those who do not find a donor. Umbilical cord blood offers the advantages of easy procurement, the absence of risks to donors, the reduced risk of transmitting infections, immediate availability of cryopreserved samples and acceptance of mismatches at two of the six antigens. Although UD-UCB transplantation is a viable option for children, it is seldom considered for adults. The great divergency between body weight and the number of hematopoietic cells in a standard cord blood unit, particularly if associated with a two-antigen mismatch, increases the risk of graft failure and delays hematopoietic reconstitution. Work on full-haplotype mismatched transplants has been proceeding for over 20 years. Originally, outcome in leukemia patients was disappointing because of high incidence of severe graft-vs.-host disease in T-replete transplants and high rejection rates in T-cell-depleted transplants. The breakthrough came with the use of a megadose of T-cell-depleted progenitor cells after a high-intensity conditioning regimen. Treating end-stage patients inevitably confounded clinical outcome in the early pilot studies. Today, high-risk acute leukemia patients are treated at less advanced stages of disease, receive a reasonably well tolerated conditioning regimen, and benefit from advances in post-transplant immunological reconstitution. All these factors contribute to markedly reduce transplant-related mortality. Overall, event-free survival and transplant-related mortality compare favorably with reports from unrelated matched transplants. T-cell-depleted megadose stem cell transplant from a mismatched family member, who is immediately available, can be offered as a viable option to candidates with high-risk acute leukemias.

Acute Disease↗
PubMed2002

Analysis of donor NK and T cells infused in patients undergoing MHC-matched allogeneic hematopoietic transplantation.

We retrospectively analyzed the percentages and absolute numbers of T cells, natural killer (NK) cells and NK cell subsets in cryopreserved samples of either bone marrow or blood non-T cell-depleted allogeneic MHC-matched hematopoietic grafts. Using flow cytometry, we found higher numbers of NK cells in aphereses than in bone marrow collections. We further investigated the distribution of NK cell subsets, defined by the cell surface expression of MHC class I-specific receptors, in these allogeneic grafts. The distribution of NK cell subsets from the two different origins were similar, with the exception of the CD158a/h(+) NK cell subset, whose size appeared to be smaller in bone marrow. The search for relations between the numbers of infused cells and post-transplantation events demonstrated that increasing numbers of infused T cells but not NK cells are related with decreased overall survival. Our study highlights the toxicity of infused T cells but not NK cells in allogeneic MHC-matched hematopoietic grafts. These data pave the way for further trials to investigate the effect of NK cell infusion in MHC-matched allogeneic transplantation, and in particular whether ex vivo NK cell expansion and activation may enhance the anti-tumoral effect of the procedure and decrease its morbidity.

Adolescent↗
PubMed1999

Use of standardized flow cytometric determinants of multidrug resistance to analyse response to remission induction chemotherapy in patients with acute myeloblastic leukaemia.

We have used a combination of flow cytometric assays to define multidrug resistance (MDR) positive and negative blasts in cryopreserved samples from 47 MRC trial patients with acute myeloblastic leukaemia (AML). Our primary test is a standardized assay for daunorubicin accumulation. Confirmatory assays for MDR comprised the cyclosporin modulation assay for rhodamine-123 uptake as a measure of functional P-glycoprotein and the measurement of lung resistance protein and multidrug resistance associated protein (with LRP-56 and MRPr1 respectively). 57% of samples had both low accumulation and at least one positive confirmatory test. 32% were MDR negative in all four assays. 15% of patients had primary chemo-resistant disease. Resistant disease rates were 22% for confirmed MDR-positive patients and 0% for confirmed MDR-negative patients (P=0.07). Complete remission was achieved in 74% of patients, with rates of 63% in confirmed MDR-positive patients and 93% in confirmed MDR-negative patients (P=0.06). The use of a standardized method for daunorubicin uptake, combined with the use of confirmatory tests, should reduce the uncertainty that is currently characteristic of MDR evaluation in leukaemia. In comparison with daunorubicin uptake, p-gp expression, measured using MRK-16 antibody, was more closely associated with remission rates (P =0.01). This suggests an additional role for p-glycoprotein in mediating drug resistance beyond that of a drug efflux pump.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Contrasting in vitro effects for the combination of fludarabine, cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (FLAG) compared with daunorubicin and Ara-C in P-glycoprotein-positive and P-glycoprotein-negative acute myeloblastic leukaemia.

It has been suggested that the FLAG remission induction regimen comprising fludarabine (F-ara), cytosine arabinoside (Ara-C) and granulocyte colony-stimulating factor (G-CSF) may be capable of overcoming P-glycoprotein (P-gp)-related multidrug resistance (MDR) in patients with acute myeloblastic leukaemia (AML). We have investigated the in vitro response of P-gp-positive and -negative AML clones to FLAG and compared this with their response to treatment with Ara-C and daunorubicin (DNR). Twenty-four cryopreserved samples from patients with AML were studied using a flow cytometric technique for the enumeration of viable (7-amino actinomycin D negative) cells. Samples consisted of 12 P-gp-positive and 12 P-gp-negative cases, as measured by the MRK16 antibody. The results were analysed by calculating the comparative drug resistance (CDR), i.e. the percentage cell death caused by Ara-C + DNR subtracted from the percentage cell death, caused by FLAG after 48 h incubation in suspension culture. P-gp-positive clones were shown to have a significantly higher CDR than P-gp-negative clones (P = 0. 001). Furthermore, a significant positive correlation (r2 = 0.40, P < 0.01) was found between P-gp protein expression and CDR. However, P-gp function, measured using cyclosporin modulation of rhodamine 123 (R123) uptake, was not associated with the CDR, demonstrating that there are other properties of P-gp, besides its role in drug efflux, that modulate the responsiveness of AML blasts to chemotherapy. These results are consistent with a potential benefit for FLAG in P-gp-positive AML, but not P-gp-negative AML, compared with standard anthracycline and Ara-C therapy.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed2000

Apparent founder effect during the early years of the San Francisco HIV type 1 epidemic (1978-1979).

HIV-1 envelope sequence variants were RT-PCR amplified from serum samples cryopreserved in San Francisco in 1978-1979. The HIV-1 subtype B env V3-V5 sequences from four homosexual men clustered phylogenetically, with a median nucleotide distance of 2.8%, reflecting a recent common origin. These early U.S. HIV-1 env variants mapped close to the phylogenetic root of the subtype B tree while env variants collected in the United States throughout the 1980s and 1990s showed, on average, increasing genetic diversity and divergence from the subtype B consensus sequence. These results indicate that the majority of HIV-1 currently circulating in the United States may be descended from an initial introduction and rapid spread during the mid- to late 1970s of subtype B viruses with limited variability (i.e., a founder effect). As expected from the starburst-shaped phylogeny of HIV-1 subtype B, contemporary U.S. strains were, on average, more closely related at the nucleic acid and amino acid levels to the earlier 1978-1979 env variants than to each other. The growing levels of HIV-1 genetic diversity, one of multiple obstacles in designing a protective vaccine, may therefore be mitigated by using epidemic founding variants as antigenic strains for protection against contemporary strains.

AIDS Vaccines↗
PubMed2004

Changes in T cell receptor excision DNA circle (TREC) levels in HIV type 1-infected subjects pre- and post-highly active antiretroviral therapy.

The T cell receptor excision DNA circle (TREC) level is an independent predictor of HIV-1 disease prognosis. We studied the temporal changes in TREC levels prior to and after highly active antiretroviral therapy (HAART) in a cohort of 131 Greek men with hemophilia who were followed up for up to 20 years since seroconversion (SC). TREC levels were determined in all available cryopreserved samples of peripheral blood mononuclear cells (PBMCs) using a multiplex real-time polymerase chain reaction (PCR) assay. Trends in log(10) TREC values were described using random effects models. Prior to HAART initiation TREC levels tended to decrease over time (mean rate of drop 19% per year; 95% CI: 16-22%). Initial TREC values were higher with younger age at SC, but the subsequent rate of drop did not differ significantly by age at SC. There was a monotonic relationship between baseline HIV-RNA levels and TREC slopes with steeper slopes at higher levels of HIV-RNA. The TREC slopes differed significantly by clinical outcome being steeper in subjects who progressed to AIDS sooner. After HAART initiation, TREC values tended to increase on average by 35% per year (95% CI: -7-94%) but the increase was evident only in subjects with a pre-HAART CD4 count below 80 cells/microl. TREC values, which likely represent a simple indicator of naive T-lymphocyte reserve, may be a clinically useful marker for long-term prognosis of HIV-1 infection and for immune reconstitution after successful HAART.

Adolescent↗
PubMed2004

Semen parameters of a semen donor before and after infection with human immunodeficiency virus type 1: case report.

Semen samples from a donor who seroconverted for human immunodeficiency virus type 1 (HIV-1) during the period that he was donating at our clinic were stored before and after infection. Semen analysis was done on all of these samples before cryopreservation. Retrospectively, both qualitative and quantitative HIV-1 testing was performed on the cryopreserved semen samples to determine the time of primary HIV-1 infection. After HIV-1 infection, semen volume, sperm motility and the percentage of spermatozoa with normal morphology were reduced compared with the same parameters before HIV-1 infection. HIV-1 RNA was intermittently detectable in semen. HIV-1 infection led to a reduction in semen volume, sperm motility and normal sperm morphology in this donor. However, the clinical significance of these findings is unclear. A longitudinal cohort study on the effects of HIV-1 infection on semen quality is necessary to confirm these findings.

Adult↗
PubMed1994

Flow cytometric detection of proliferative cells in leukemias.

We studied the proliferative activity of leukemic cells obtained from the peripheral blood and bone marrow of 34 patients; 30 with acute leukemia and 4 with chronic myelogenous leukemia in blastic crisis. Flow cytometry was performed using monoclonal antibody against DNA polymerase alpha. Since fresh and frozen cells showed virtually identical DNA polymerase alpha-positive populations and flow cytometric histograms, 52 cryopreserved samples (25 from peripheral blood and 27 from bone marrow) were used in this study. The DNA polymerase alpha-positive population ranged from 20.4% to 84.7% in peripheral blood, and from 6.5% to 92.1% in bone marrow. A positive correlation (r = 0.76, P < 0.01) was found between DNA polymerase alpha-positive populations in peripheral blood and bone marrow from the same patient. This suggests that the DNA polymerase alpha-positive population in the bone marrow can be estimated from that in peripheral blood. No relationship was observed between the positive population and the response to chemotherapy. Statistical analyses for all cases showed no relationship between the DNA polymerase alpha-positive population and either the tumor cell count or time to reach a nadir. However, a negative correlation was observed between the positive population in bone marrow samples and the time to reach a nadir (r = -0.64, P < 0.05) in those patients who achieved a complete response. In addition, in the cases of acute non-lymphocytic leukemia who did not respond to chemotherapy, a positive correlation was observed between the tumor cell count in bone marrow and the DNA polymerase alpha-positive population (r = 0.93, P < 0.01). Thus, the method described here provides a simple and time-efficient means of detecting the proliferative activity of leukemic cells, which is a useful parameter in the treatment of leukemia.

Adolescent↗
PubMed1993

'Spontaneous' transformation as aberrant epigenesis.

The NIH 3T3 line of cells has particular advantages for studying the dynamics of change in cellular phenotype in response to environmental conditions. Similar to stem cell growth during development, the cell line changes its phenotype under growth constraints that elicit differentiation or, alternatively, it maintains its original state over many replication cycles when grown without constraint. Unlike many cell types which respond by undergoing terminal differentiation, the NIH 3T3 cells continue to multiply indefinitely following an induced alteration in phenotype; the heritability of this change may thus be analyzed under stringent conditions of cell culture. During the course of over two years of frequent passage at low density in high calf serum (CS) concentration, a new subline developed which exhibited a consistent capacity to respond quickly and pervasively to growth constraints with an increase in saturation density, development of transformed foci in confluent cultures and altered appearance of isolated colonies. A retrospective study was undertaken, with cells from cryopreserved samples, of the course of changes in responsiveness of the cells to growth constraint leading up to the highly responsive state. Three stages were discerned, the first with an initially high capacity of a small fraction of cells to produce diffuse foci, but with a rapid decline in this capacity with frequent low density passages; the second stage, extending over more than 200 passages, of refractoriness to transformation; and the third stage (which probably arose by mutation) in which there is a consistent transformation-related response by the entire population to growth constraint, a response which has remained relatively constant over some 100 passages. A striking and novel feature of the third stage is seen on cloning the cells. Almost all the colonies obtained by cloning cells from post-confluent, growth-inhibited cultures are distinctly different in morphology from those obtained by cloning cells from the frequent low density passages. The pervasiveness of this morphological change among the clones is unmistakable evidence for a heritable adaptive response to growth constraint by most if not all of the cells in the population. The population-wide response of the cells of the third stage offers the opportunity for a rigorous, quantitative analysis of the nature of this type of persistent cellular change. Although cells of the third stage may be of mutational origin, their pervasive heritable response once the variant population is established supports the concept of progressive state selection which postulates that transformation can arise by the continuous fluctuation of growth states within cells, accompanied by the progressive selection of those states best suited to function under the selecting constraint. Relevance of the concept to the process of differentiation under growth constraint is considered.

3T3 Cells↗
PubMed1997

Relation of impaired lymphocyte proliferative function to other major human immunodeficiency virus type 1-induced immunological changes.

Human immunodeficiency virus (HIV) type 1 (HIV-1) induces impairment of immune function reflected in reduced lymphocyte proliferative responses. Many other immune changes are induced by HIV-1, but their relationship to lymphocyte functional defects is not known. The present study was designed to correlate functional defects with other HIV disease parameters. Cryopreserved samples from 118 HIV-1-positive subjects and 40 seronegative individuals were examined. The main findings were that impaired proliferative responses to mitogens correlated with (i) decreased cell surface expression of the interleukin-2 receptor (CD25), (ii) increased expression of HLA-DR antigens on CD4 cells, (iii) reduced CD4 and increased CD8 cell numbers, and (iv) increased levels of serum immune complex dissociated p24 antigen. However, impaired function was not associated with increased serum neopterin, beta2-microglobulin, or soluble interleukin-2 receptor or with CD38 antigen expression on lymphocytes. In summary, proliferative functional impairment correlated with some, but not all, immunological changes associated with HIV-1 infection. Most of the phenotypic markers that correlated with altered function are cell surface molecules with significant roles in lymphocyte proliferation and were associated primarily with CD4 cells, compatible with the view that dysregulation of CD4 cells is responsible for impaired function.

Antigen-Antibody Complex↗
PubMed1992

Feasibility of the fluorometric microculture cytotoxicity assay (FMCA) for cytotoxic drug sensitivity testing of tumor cells from patients with acute lymphoblastic leukemia.

The automated fluorometric microculture cytotoxicity assay (FMCA) was used for chemotherapeutic drug sensitivity testing of fresh and cryopreserved tumor cells from patients with acute lymphoblastic leukemia (ALL) at diagnosis and relapse. The technique success rate was 87% for fresh and 81% for cryopreserved samples. Up to 16 different cytotoxic drugs were routinely tested, but neither asparaginase nor methotrexate produced dose-response related cell kill. FMCA data showed good correlation to the well established Disc assay and the drug sensitivity reported by the FMCA was in good agreement with known clinical activity. Samples from children and initial ALL tended to be more drug sensitive than those from adults and ALL at relapse, respectively. For 36 samples clinical outcome was correlated to the quartile position in comparison to all other samples for the most in vitro active drug actually given to the patient. For patients with samples in the first, second, third, and fourth quartiles, the probabilities of complete remission were 89, 57, 38, and 0%, respectively. Using the median value as cut-off line, the sensitivity and specificity of the assay were 87 and 62%, respectively. It is concluded that the FMCA with a minimum of effort and with high success rate report clinically relevant drug sensitivity profiles for ALL.

Antineoplastic Agents↗
PubMed1986

Immunodeficiency in rhesus monkeys associated with the original Mason-Pfizer monkey virus.

The Mason-Pfizer monkey virus (MPMV) was reisolated from a cryopreserved sample of the original MPMV-containing rhesus breast carcinoma, and complete integrated MPMV provirus was detected in chromosomal DNA of this tumor. Reanalysis of the in vivo pathogenicity and molecular character of MPMV reisolated from the rhesus breast tumor and analysis of the original MPMV after long-term in vitro propagation in human and rhesus cells show that the original MPMV produces an acquired immunodeficiency similar to that caused by the recently described simian acquired immune deficiency syndrome type D retroviruses, and the MPMV genome and its immunosuppressive effect in vivo have remained stable despite prolonged in vitro passage in human and rhesus cells.

Acquired Immunodeficiency Syndrome↗
PubMed1996

BCR-ABL expression in different subpopulations of functionally characterized Ph+ CD34+ cells from patients with chronic myeloid leukemia.

In patients with chronic myeloid leukemia (CML), the leukemic (BCR-ABL+/Ph+) clone typically includes cells belonging to all of the myeloid lineages and frequently some B cells. From such observations it has been inferred that the initial BCR-ABL gene rearrangement event occurs in a pluripotent hematopoietic stem cell and that the clone subsequently generated is maintained by a subpopulation of neoplastic, BCR-ABL-expressing cells that retain at least some of the defining properties of normal hematopoietic stem cells. To test this hypothesis directly, we isolated various subpopulations of CD34+ cells from fresh or cryopreserved samples of peripheral blood from 5 CML patients with high white blood cell counts, 4 of which were selected because of their exclusive content of Ph+ progenitors (both colony-forming cells and long-term culture-initiating cells [LTC-IC]). Cells in each of the CD34+ subpopulations isolated were examined for the presence of BCR-ABL mRNA using a reverse transcriptase-polymerase chain reaction technique that reproducibly gave a positive signal from single K562 cells. BCR-ABL mRNA was detected in 117 of 147 samples (80%) in which actin mRNA was demonstrable. This included 60% to 90% of a large number of individually analyzed CD34+ cells including 46 single CD34+CD71-CD38- cells and 27 single CD34+CD71+CD38+ cells from 3 patients. In 2 of these cases, the same populations also contained a very high frequency of Ph+ LTC-IC. Our findings demonstrate BCR-ABL gene expression in neoplastic cells with functional as well as surface marker characteristics of very primitive normal hematopoietic cells. This implicates the BCR-ABL gene product directly in the acquisition by these cells of properties that alter their interactions with the microenvironment and deregulate their proliferation control.

ADP-ribosyl Cyclase↗
PubMed1997

Cell proliferation detected by DNA polymerase alpha in acute leukemias.

Fifty-nine patients with acute leukemia were studied by flow cytometry using monoclonal antibody against DNA polymerase alpha. Since fresh and frozen cells showed identical flow cytometric histograms, 86 cryopreserved samples (39 from peripheral blood and 47 from bone marrow) were used in this study. The DNA polymerase alpha-positive population ranged from 16.3 to 84.7% in peripheral blood, and from 6.5 to 92.1% in bone marrow. A positive correlation (r = 0.80; p < 0.01) was found between DNA polymerase alpha-positive populations in peripheral blood and bone marrow from the same patient. This suggests that the DNA polymerase alpha-positive population in the bone marrow can be estimated from that in peripheral blood. A negative correlation was observed between the positive population in bone marrow samples and the time to reach a nadir (r = -0.58: p < 0.01), while a positive correlation was found between the tumor cell count in bone marrow and the DNA polymerase alpha-positive population (r = 0.64; p < 0.01) in patients who responded to chemotherapy.

Acute Disease↗
PubMed2005

Systematic factor optimization for cryopreservation of shipped sperm samples of diploid Pacific Oysters, Crassostrea gigas.

Despite some 26 published reports addressing oyster sperm cryopreservation, systematic factor optimization is lacking, and sperm cryopreservation has not yet found application in aquaculture on a commercial scale. In this study, the effects of cooling rate, single or combined cryoprotectants at various concentrations, equilibration time (exposure to cryoprotectant), straw size, and cooling method were evaluated for protocol optimization of shipped sperm samples from diploid oysters. Evaluation of cooling rates revealed an optimal rate of 5 degrees C/min to -30 degrees C followed by cooling at 45 degrees C/min to -80 degrees C before plunging into liquid nitrogen. Screening of single or combined cryoprotectants at various concentrations suggested that a low concentration (2%) of polyethylene glycol (FW 200) was effective in retaining post-thaw motility and fertilizing capability when combined with permeating cryoprotetcants such as dimethyl sulfoxide (DMSO), methanol (MeOH), and propylene glycol (P-glycol). However, polyethylene glycol alone was not as effective as MeOH, DMSO, and P-glycol when using the same methods. The highest post-thaw motility (70%) and percent fertilization (98%) were obtained for samples cryopreserved with 6% MeOH. However, this does not exclude other cryoprotectants such as DMSO or P-glycol identified as effective agents in other studies. There was no significant difference in post-thaw motility between straw sizes of 0.25- and 0.5-ml. Equilibration time (exposure to cryoprotectant) of 60 min could be beneficial when the cryoprotectant concentration is low and solution is added in a step-wise fashion at low temperature. Differences in post-thaw sperm quality (e.g., motility or percent fertilization) among individual males were evident in this research. As a consequence, a generalized classification describing males with different tolerances (broad, intermediate, and narrow) to cryopreservation was developed. This classification could be applied to strain or species differences in tolerances to the cryopreservation process. The present study demonstrated that oyster sperm could be collected and shipped chilled to another facility for cryopreservation, and that it could be shipped back to the hatchery for fertilization performed at a production scale yielding live larvae with >90% fertilization. Given the existence of facilities for commercial-scale cryopreservation of dairy bull sperm, the methods developed in the present study for oysters provide a template for the potential commercialization of cryopreserved sperm in aquatic species.

Animals↗
PubMed1989

Comparison of human long-term bone marrow cultures (HLTBMCs) established from fresh and post-cryopreservation bone marrow samples from living and cadaver donors.

Human long-term bone marrow cultures (HLTBMCs) were established from thawed post-cryopreservation, as well as from cadaver donor bone marrow (BM) samples. The longevity was similar in the different series of HLTBMCs examined. CFU-GM could be cultured out of cadaver donor BM. This indicates that previously healthy people, under the conditions generally accepted as suitable for organ donation, could become suitable donors for allogeneic BM transplantation.

Bone Marrow Cells↗
PubMed1981

A method for detecting aryl hydrocarbon hydroxylase activities in cryopreserved human lymphocytes.

Aryl hydrocarbon hydroxylase (AHH) activity, NADH-dependent cytochrome c reductase (cyt c) activity, and [3H]thymidine (3H-TdR) incorporation were monitored in human lymphocytes cryopreserved for periods up to 1 year. A standard procedure for freezing, thawing and culturing of these lymphocytes was developed. Kinetics for expression of benz[a]anthracene-(BA)-induced AHH activity, cyt c activity, and 3H-TdR incorporation were similar in both freshly cultured and cryopreserved cells. Lymphocyte samples from 10 individuals were collected once per month over a 3-month period and cells were either cultured at the time of donation or cryopreserved for later assay. Results indicated that the cryopreserved lymphocytes efficiently responded to mitogen activation. The intra-individual variation in AHH activities was reduced in the cryopreserved lymphocytes compared to the freshly cultured cells, and the relative ranking of these individuals in terms of their AHH activities remained constant for both fresh and cryopreserved samples. Cryopreservation seems to offer significant advantages over the freshly cultured lymphocytes because it allows for lymphocyte samples to be collected in diverse geological locations and over extended periods of time and yet permits for the culture and assay of all the cell samples at exactly the same time.

Aryl Hydrocarbon Hydroxylases↗
PubMed1996

Fresh and cryopreserved ovarian tissue samples from donors with lymphoma transmit the cancer to graft recipients.

Girls and young women who require ovariectomy or cancer therapy may consider having their own eggs, embryos or ovarian tissue stored (cryopreserved) for their own future use. Ovarian tissue is simple to collect and contains large numbers of germ cells. Transplantation of fresh and frozen-thawed ovarian tissue in healthy sheep and mice has resulted in normal live young. Similar techniques may be effective in the human but it is unclear whether ovarian tissue cryopreservation and grafting is suitable for ovaries from individuals with cancer or infections. If cancer cells were present in an ovary at the time of collection and survived cryopreservation and grafting they could establish cancer in the recipient. We therefore performed ovarian cryopreservation and transplantation trials using a mouse lymphoma model. This established that the lymphoma was transmitted by grafts of both fresh and frozen ovarian tissue. The normal healthy recipient mice died 9-43 days after receiving a small piece (1 mm3) of ovarian tissue from a donor with lymphoma. We conclude that ovarian tissue which is collected, cryopreserved and grafted while it contains cancer cells has the potential to spread the cancer to the graft recipient.

Aging↗