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Christopher D Hillyer

Publications and source records attributed to Christopher D Hillyer.

At least 19 recordsLinked to original sources
PubMed2007

Transfusion-transmitted cytomegalovirus: lessons from a murine model.

Transfusion-transmitted cytomegalovirus (CMV) infection (TT-CMV) continues to complicate blood transfusion therapy, which can lead to severe morbidity or mortality in immunocompromised or immuno-immature recipients. The biological mechanisms that underlie TT-CMV (eg, viral latency in donor monocytes or stimulatory signals in the transfusion recipient leading to cytomegalovirus reactivation) are difficult to study in humans, but can be addressed in animal models. In this review, we discuss a mouse blood transfusion model, which can be used to investigate these issues as well as to validate methods to prevent TT-CMV in at-risk patients.

Animals↗
PubMed2006

Transfusion-transmitted cytomegalovirus (CMV) infections in a murine model: characterization of CMV-infected donor mice.

BACKGROUND: Donor and recipient mechanisms that modulate the incidence and severity of transfusion-transmitted cytomegalovirus (TT-CMV) are unclear. The kinetics of murine CMV (MCMV) infection in the peripheral blood of donor mice were investigated to determine the utility of this model for studying TT-CMV. STUDY DESIGN AND METHODS: BALB/cByJ mice, experimentally infected with Smith strain MCMV, were killed at serial time points up to 28 days after infection. Peritoneal exudate cells (PECs), peripheral blood white blood cells (WBCs), plasma, and marrow were tested for MCMV DNA with quantitative polymerase chain reaction (PCR), replication-competent virus with quantitative culture, and transcription of viral genes with reverse transcription (RT)-PCR targeted at the immediate-early 1 (ie1) gene. RESULTS: PECs, macrophages infected by MCMV shortly after intraperitoneal inoculation, demonstrated high mean levels of MCMV DNA (10(5)-10(7) genome equivalents [geqs]/10(5) PECs), virus production (10(1)-10(4) infectious virions/10(5) PECs), and ie1 gene transcription, demonstrating productive infection. In contrast, while MCMV loads averaged 10(4) to 10(6) geqs per 10(5) peripheral WBCs, all WBC samples were uniformly negative for MCMV ie1 expression by RT-PCR and for culturable virus, consistent with latent MCMV infection. Plasma and marrow showed lower viral loads than WBCs and PECs and were all negative by culture and RT-PCR analysis. CONCLUSIONS: Following experimental MCMV infection, murine peripheral blood WBCs appear to be latently infected with virus (MCMV DNA-positive; MCMV RNA-negative; MCMV culture-negative), similar to the latently infected human monocytes in peripheral blood of CMV-seropositive donors. These donor kinetics suggest that the experimental MCMV system can be used to effectively model the mechanisms of TT-CMV infections in humans.

Animals↗
PubMed2006

Recipient inflammation affects the frequency and magnitude of immunization to transfused red blood cells.

BACKGROUND: Most alloantigens on transfused red blood cells (RBCs) are weakly immunogenic, with only a 2 to 6 percent overall immunization rate even in patients receiving multiple transfusions. Although recipient genetics may contribute to responder and/or nonresponder status, in most cases HLA type does not predict humoral response to RBC antigens. In contrast, rates of alloimmunization do correspond to the underlying disease status of transfusion recipients, suggesting that acquired host factors may play an important role. In this context, it was hypothesized that the inflammatory status of a transfusion recipient would influence immunization to transfused RBCs. STUDY DESIGN AND METHODS: A novel murine model for alloimmunization to RBC antigens was developed with the mHEL mouse, which expresses hen egg lysozyme (HEL) as a model blood group antigen. Leukoreduced mHEL RBCs were transfused into wild-type recipient mice, and anti-HEL responses were monitored. To test the stated hypothesis, some recipient animals were injected with polyinosinic polycytidylic acid (poly(I:C)), a synthetic double-stranded RNA molecule that induces viral-like inflammation. RESULTS: Similar to the immunogenicity of most RBC antigens in humans, transfusion of mHEL RBCs into uninflamed mice was only a weak immunogen. In contrast, poly(I:C)-treated mice had a significant increase in both the frequency and the magnitude of alloimmunization to the mHEL antigen. CONCLUSIONS: These findings demonstrate that recipient inflammation with poly(I:C) significantly enhances humoral immunization to transfused alloantigens in a murine model. Moreover, these data suggest that the inflammatory status of human transfusion recipients may regulate the immunogenicity of transfused RBCs.

Animals↗
PubMed2006

Prevalence of selected viral infections among blood donors deferred for potential risk to blood safety.

BACKGROUND: Health history questions identify blood donors believed to pose a higher risk of transmission of infectious diseases. This study assesses the current impact of some of these questions on blood safety as reflected by infectious disease markers. STUDY DESIGN AND METHODS: Donors who were deferred from donating blood due to health history question(s) were recruited at four different regions of the American Red Cross Blood Services. A blood sample was tested for serologic markers of blood-borne infections as performed for accepted blood donors. RESULTS: Of 497 deferred donors enrolled, 29 donors were deferred for having had "yellow jaundice, liver disease, or hepatitis since the age of 11" (Question 3), 1 of whom had hepatitis C virus antibodies (anti-HCV) and hepatitis B core antigen antibodies (anti-HBc), 2 had anti-HBc, and 1 had anti-HCV (p < 0.05 for both markers). Among 37 donors deferred for having "ever tested positive for hepatitis" (Question 4), 1 had hepatitis B surface antigen and anti-HBc and 3 had anti-HBc (p < 0.05 for both markers). Of 14 donors deferred for "having ever used a needle, even once, to take any illegal or nonprescription drug" (Question 12), 1 had anti-HCV, human T-lymphotropic virus-I antibodies and anti-HBc, 1 had anti-HCV and anti-HBc, and 2 had anti-HCV (p < 0.05 for all three markers). CONCLUSIONS: Blood donors deferred for standard blood donor questions regarding risk of viral hepatitis as well as those with a history of intravenous drug use were more likely to have higher hepatitis marker rates than those who were not deferred. No significant findings were identified for other markers or questions.

Antibodies, Viral↗
PubMed2005

Nonhemolytic antibody-induced loss of erythrocyte surface antigen.

Transfusion of red blood cells (RBCs) into patients with anti-donor RBC antibodies (crossmatch-incompatible transfusion) can result in lethal antibody-mediated hemolysis. Less well appreciated is the ability of anti-RBC antibodies to specifically remove their target antigen from donor RBCs without compromising cell survival or adversely affecting the transfusion recipient. In an effort to elucidate the mechanistic details of this process, we describe the first animal model of nonhemolytic antibody-induced RBC antigen loss. RBCs from transgenic mHEL mice express surface hen egg lysozyme (HEL) as a transmembrane protein. Transfusion of mHEL RBCs into mice immunized with HEL results in selective loss of HEL antigen from donor RBCs without affecting other blood group antigens or reducing the circulatory life span of the transfused RBCs. While this process does not require the presence of a spleen, it requires both anti-RBC immunoglobulin G (IgG) antibodies and the FcgammaIII receptor. These studies provide mechanistic insight into the phenomenon of antigen loss during incompatible transfusion in humans.

Animals↗
PubMed2005

Amotosalen-treated donor T cells have polyclonal antigen-specific long-term function without graft-versus-host disease after allogeneic bone marrow transplantation.

We have previously shown that amotosalen HCl (S-59 psoralen)-treated donor splenocytes, which have limited proliferative capacity in vitro, can protect major histocompatibility complex-mismatched bone marrow transplant (BMT) recipients from lethal murine cytomegalovirus infection without causing graft-versus-host disease. In this study, we further investigated the effects of amotosalen-treated donor T cells on immune reconstitution after allogeneic BMT. We were surprised to find that amotosalen-treated donor T cells persisted long-term in vivo, comprising 6% to 10% on average of the T-cell compartment of transplant recipients at 4 months after transplantation. Donor T cells derived from amotosalen-treated splenocytes were predominantly polyclonal CD44 hi/int CD8 + memory T cells and were functionally active, synthesizing interferon gamma in response to stimulation with murine cytomegalovirus antigen. Amotosalen-treated donor T cells, reisolated from BMT recipients' spleens >/=4 months after transplantation, proliferated in vitro, thus indicating repair of amotosalen-mediated DNA cross-links. Compared with infusion of untreated donor splenocytes, amotosalen-treated cells enhanced thymopoiesis by bone marrow-derived stem cells in BMT recipients. However, amotosalen treatment abrogated the thymopoietic activity of lymphoid progenitor cells among the donor splenocytes. Thus, infusion of amotosalen-treated donor T cells produced rapid immune reconstitution after major histocompatibility complex-mismatched BMT by transferring long-lived polyclonal memory T cells with antiviral activity and also by enhancing bone marrow-derived thymopoiesis. This is a novel approach to adoptive immunotherapy in allogeneic BMT.

Animals↗
PubMed2005

Comparison of cytomegalovirus polymerase chain reaction and serology for screening umbilical cord blood components.

BACKGROUND: Recipients of umbilical cord blood (UCB) transplants are susceptible to opportunistic infections, including cytomegalovirus (CMV). To prevent CMV transmission from UCB donors, most laboratories perform serology on corresponding maternal samples and quarantine units when the mother has immunoglobulin M (IgM) anti-CMV. STUDY DESIGN AND METHODS: UCB units and associated samples (UCB plasma and red cell pellet; maternal whole blood and serum) from two cord blood banks were tested with two validated CMV polymerase chain reaction assays (UL54 and UL93 targets). Results were compared with maternal CMV serology (IgG and IgM). RESULTS: Only 4 of 48 (8.3%) quarantined CMV IgM-positive units were also CMV nucleic acid testing (NAT)-positive (651-68,600 copies/mL). In contrast, 1 of 200 "CMV-safe" UCB units (CMV IgM-equivocal or -negative) had CMV DNA (0.5%). The corresponding maternal samples were CMV NAT-negative. Positive maternal IgM serology demonstrates only modest sensitivity (80%) and specificity (82%) and poor positive predictive value (8%), when correlated with the presence of CMV DNA in UCB units. CONCLUSION: CMV NAT may be a useful adjunct to serologic screening, potentially reducing wastage of IgM-positive and NAT-negative units while also detecting potentially infectious units that would pass serologic screening. A prospective clinical trial to further evaluate the role of CMV NAT in UCB transplantation appears warranted.

Cells, Cultured↗
PubMed2004

Effect of mediators of innate immunity and inflammation on CD8+ veto cells.

BACKGROUND: Methods of allotolerance induction that are successful in mice often fail in primates. Activators of innate immunity derived from microbial pathogens, which are present in primate populations but not in pathogen-free mouse colonies, have been shown to overcome tolerance induction by co-stimulatory blockade or regulatory T cells. Unlike other strategies, veto cells promote long-term allograft survival in primates. Accordingly, the authors hypothesized that veto cells are resistant to the effects of innate immune activation. METHODS: Using mixed lymphocyte reactions as a model of alloimmunization, the authors assessed the effect of inflammatory mediators on veto cell activity. RESULTS.: The authors demonstrate that the activity of veto cells is unaltered by lipopolysaccharide, double-stranded RNA, or interferon-gamma. Tumor necrosis factor-alpha modestly inhibited the veto effect, but only when veto cells were limiting. CONCLUSIONS: These findings may help to explain why veto cell-based therapies are more effective than other approaches in primate populations.

Animals↗
PubMed2004

Unappreciated risk factors for transplant patients: HLA antibodies in blood components.

One of the more aggressive approaches in renal transplantation is the use of plasmapheresis (PP) and intravenous immunoglobulin to eliminate donor-directed human leukocyte antigen (HLA) alloantibodies. A potential complication of a PP protocol is iatrogenic hypocoagulability resulting from the removal of coagulation factors. To prevent bleeding, hypocoagulable patients may require transfusions with fresh frozen plasma (FFP) and/or cryoprecipitate (Cryo). Although HLA alloantibodies in these components have been linked to complications, such as transfusion-related acute lung injury (TRALI), whether they cause complications following transfusion into allograft recipients is unknown. The incidence of complications would be dependent, in part, upon the frequency of HLA alloantibodies in the various blood components. In this study, segments from 77 units of FFP, 66 units of Cryo, 106 units of packed red blood cells (RBCs), and 59 units of apheresis platelets (Plts) were tested for antibodies to HLA class I and class II antigens using FlowPRA, an HLA antigen-specific flow cytometric assay. On average, 22% of blood components tested contained HLA alloantibodies, tenfold greater than previously reported. This unappreciated frequency of HLA alloantibodies in blood components may pose a risk to transplant patients requiring transfusions by promoting allograft dysfunction or loss.

Antibodies↗
PubMed2004

Leukoreduction filtration of blood with sickle cell trait.

Leukoreduction of cellular blood products by filtration has been shown to decrease the incidence of febrile nonhemolytic transfusion reactions, transmission of leukocyte-associated viruses, and HLA alloimmunization. However, the increasing popularity of leukofiltering blood products over the past few years has highlighted specific filtration failures associated with sickle trait (hemoglobin AS) blood. Sickle trait blood does not filter adequately, which leads to prolonged or incomplete filtration, often with a higher number of postfiltration leukocytes in the unit than the mandated minimal residual volume of <1 to 5 x 10(6). This review of the literature highlights various parameters that affect the adequacy of filtration of blood products, including effects of temperature, pH, osmolarity, type of anticoagulant, time of storage, and oxygen saturation of the blood unit. A combination of these factors likely contributes to the frequent filtration failure of sickle trait products. Although blood units are not routinely screened for sickle cell hemoglobin, administration of units with sickle trait red blood cells can be disadvantageous to certain patient populations. This review concludes with a discussion of different approaches to screening blood units for sickle cell trait.

Anticoagulants↗
PubMed2004

Improved method for fluorescence cytometric immunohematology testing.

BACKGROUND: A method for accurate immunohematology testing by fluorescence cytometry (FC) was previously described. Nevertheless, the use of vacuum filtration to wash RBCs and a standard-flow cytometer for data acquisition hindered efforts to incorporate this method into an automated platform. STUDY DESIGN AND METHODS: A modified procedure was developed that used low-speed centrifugation of 96-well filter plates for RBC staining. Small-footprint benchtop capillary cytometers (PCA and PCA-96, Guava Technologies, Inc.) were used for data acquisition. Authentic clinical samples from hospitalized patients were tested for ABO group and the presence of D antigen (n = 749) as well as for the presence of RBC alloantibodies (n = 428). Challenging samples with mixed-field reactions and weak antibodies were included. Results were compared to those obtained by column agglutination technology (CAT), and discrepancies were resolved by standard tube methods. Detailed investigations of FC sensitivity and reproducibility were also performed. RESULTS: The modified FC method with the PCA determined the correct ABO group and D type for 98.7 percent of 520 samples, compared to 98.8 percent for CAT (p > 0.05). No-type-determined (NTD) rates were 1.2 percent for both methods. In testing for unexpected alloantibodies, FC determined the correct result for 98.6 percent of 215 samples, compared to 96.3 percent for CAT (p > 0.05). When samples were automatically acquired in the 96-well plate format with the PCA-96, 98.7 percent of 229 samples had correct ABO group and D type determined by FC, compared to 97.4 percent for CAT (p > 0.05). NTD rates were 0.9 and 2.6 percent, respectively. Antibody screens were accurate for 99.1 percent of 213 samples with the PCA-96, compared to 99.5 percent for CAT (p > 0.05). Further investigations demonstrated that FC with the PCA-96 was better than CAT at detecting weak anti-A (p < 0.0001) and alloantibodies. CONCLUSIONS: An improved method for FC immunohematology testing has been described. This assay was comparable in accuracy to standard CAT techniques, but had better sensitivity for detecting weak antibodies and was superior in detecting mixed-field reactions (p < 0.005). The FC method demonstrated excellent reproducibility. The compatibility of this assay with the PCA-96 capillary cytometer with plate-handling capabilities should simplify development of a completely automated platform.

Autoantibodies↗
PubMed2004

Photochemical treatment of platelet concentrates with amotosalen hydrochloride and ultraviolet A light inactivates free and latent cytomegalovirus in a murine transfusion model.

BACKGROUND: A photochemical treatment (PCT) process utilizing amotosalen hydrochloride and long wavelength UVA light has been developed to inactivate pathogens in PLTs. This study investigated the effects of amotosalen/UVA treatment on free and latent murine CMV (MCMV) in PLT preparations using a murine model of transfusion-transmitted CMV (TT-CMV). STUDY DESIGN AND METHODS: In a model of latent MCMV infection, "donor" mice received 1 x 10(6) plaque-forming units (PFUs) MCMV and were rested 14 days. Subsequently harvested, pooled, and washed WBCs were PCR positive for MCMV. Murine WBC doses of 1 x 10(4), 1 x 10(5), and 1 x 10(6) were added to human apheresis PLTs in 35 percent autologous plasma and 65 percent PLT AS (PAS). The WBC-PLT products were treated with 150 micro mol/L amotosalen and 0.6 J per cm2 UVA and transfused via tail vein injection into recipient mice. Recipients were killed on Day 14. Blood and spleens were collected and assayed for MCMV by PCR. In a parallel model of active infection with free virus, human PLT in 35 percent autologous plasma and 65 percent PAS were dosed with 1 x 10(5) and 1 x 10(6) PFUs of MCMV. All other procedures were as described above. RESULTS: In the absence of amotosalen/UVA-pretreatment, transfusion of PLT latently or actively infected with MCMV produced TT-CMV in a dose-dependent fashion. In contrast, all transfusion recipients of identical PLT preparations pretreated with amotosalen/UVA were uniformly PCR negative for MCMV (abrogation of TT-CMV; p < 0.05). CONCLUSIONS: PCT of PLT preparations with the specified doses of amotosalen hydrochloride and UVA light prevents transfusion transmission of free and latent MCMV in a murine model. These results suggest that PCT of human PLTs with amotosalen/UVA should also effectively abrogate TT-CMV in the clinical setting.

Animals↗
PubMed2004

Description and investigation of white particulate matter in additive solution-1 red blood cell units.

BACKGROUND: In January 2003, "white particulate matter" (WPM) was transiently observed in red blood cell (RBC) units collected predominately in the southeastern US. In this report, these events, their chronology, pertinent observations and investigations, and summaries and conclusions associated with WPM during the 2-week observation period are described. CHRONOLOGY AND INVESTIGATIONS: On January 27, 2003, WPM was first identified in RBCs; by January 31, 2003, 110 RBC units containing WPM had been identified. Elective surgeries were postponed. Approximately 400 RBC units containing WPM were inspected in the blood center and characterized into four types: I, II, III, and IV. A variety of preparations of aspirated WPM were made, including light and electron microscopic sections. RESULTS AND CONCLUSIONS: The rate of WPM-containing units was 1.67 percent (1 in 60 units), whereas the background incidence was less than 0.25 percent. Investigations revealed that WPM was composed of activated and nonactivated platelets (PLTs); no toxins, infectious agents, or agents of bioterrorism were identified. WPM correlated with certain variables studied, including PLT-rich components that had been centrifuged with a "hard spin" before leukoreduction and manufactured in one vendor's collection sets. Because the increased rate of appearance of WPM was a transient phenomenon, it is not clear whether this is a newly noticed or a new and different phenomenon from "aggregates" observed in the past.

Blood Specimen Collection↗
PubMed2003

Allogeneic T cells treated with amotosalen prevent lethal cytomegalovirus disease without producing graft-versus-host disease following bone marrow transplantation.

Infusion of donor antiviral T cells can provide protective immunity for recipients of hemopoietic progenitor cell transplants, but may cause graft-vs-host disease (GVHD). Current methods of separating antiviral T cells from the alloreactive T cells that produce GVHD are neither routine nor rapid. In a model of lethal murine CMV (MCMV) infection following MHC-mismatched bone marrow transplantation, infusion of MCMV-immune donor lymphocytes pretreated with the DNA cross-linking compound amotosalen prevented MCMV lethality without producing GVHD. Although 95% of mice receiving 30 x 10(6) pretreated donor lymphocytes survived beyond day +100 without MCMV disease or GVHD, all mice receiving equivalent numbers of untreated lymphocytes rapidly died of GVHD. In vitro, amotosalen blocked T cell proliferation without suppressing MCMV peptide-induced IFN-gamma production by MCMV-primed CD8(+) T cells. In vivo, pretreated lymphocytes reduced hepatic MCMV load by 4-log(10) and promoted full hemopoietic chimerism. Amotosalen-treated, MCMV tetramer-positive memory (CD44(high)) CD8(+) T cells persisted to day +100 following infusion, and expressed IFN-gamma when presented with viral peptide. Pretreated T cells were effective at preventing MCMV lethality over a wide range of concentrations. Thus, amotosalen treatment rapidly eliminates the GVHD activity of polyclonal T cells, while preserving long-term antiviral and graft facilitation effects, and may be clinically useful for routine adoptive immunotherapy.

Animals↗
PubMed2003

CMV DNA is rarely detected in healthy blood donors using validated PCR assays.

BACKGROUND: Although serologic screening or WBC reduction of blood components can reduce the incidence of transfusion-transmitted CMV (TT-CMV) infection, 'breakthrough' cases of TT-CMV still occur and may produce serious sequelae. NAT of blood components for CMV DNA has been proposed to further reduce the risks of TT-CMV. However, large-scale studies to determine the utility of validated CMV NAT assays for donor screening have not been reported. STUDY DESIGN AND METHODS: Coded whole-blood samples (n=1000) were tested for the presence of CMV DNA using two CMV PCR assays previously validated in a multicenter trial (a nested PCR assay directed at the CMV UL93 open-reading frame and the Roche Monitor assay). Corresponding plasma samples were tested in parallel for the presence of anti-CMV using other assays (Abbott CMV EIA and Fujirebio/Olympus CMV particle agglutination assays). RESULTS: In total 416 and 514 of the samples tested as CMV-seropositive and -seronegative, respectively, by both antibody assays. The remaining 70 samples had discrepant serology results. Only 2 of the 1000 samples (both seropositive) had reproducibly detectable CMV DNA (positive in at least three of four replicates). CMV DNA was not reproducibly detected in seronegative samples or in samples with discrepant serology results. CONCLUSIONS: Although previous investigations showed frequent detection of CMV DNA in healthy CMV-seropositive (and some seronegative) blood donors, these studies were relatively small and the performance characteristics of their assays were difficult to evaluate. In contrast, the present large cross-sectional study of US donors utilized two previously validated PCR assays and demonstrated that CMV DNA is only rarely detectable in seropositive donors. Thus, the use of CMV PCR assays with optimal performance characteristics did not increase the detection of potentially infectious blood components beyond that provided by current serologic screening assays.

Antibodies, Viral↗
PubMed2003

An automatable format for accurate immunohematology testing by flow cytometry.

BACKGROUND: Current immunohematology testing methods have limitations including cost, throughput, and adaptability to automation. Furthermore, current automated and semiautomated workstations cannot accommodate many other tests relevant to blood transfusion. STUDY DESIGN AND METHODS: Authentic clinical samples from hospitalized patients were tested for ABO group, D type, and presence of RBC alloantibodies by column agglutination technology (CAT), standard tube methods, and a recently developed flow cytometry (FC) technique. Included were challenging samples with rouleaux, autoantibodies, mixed-field reactions, and weak antibodies. Antibody staining of RBCs for FC was initially performed in test tubes and subsequently in microtiter filter plates interfaced with a vacuum manifold. RESULTS: When antibody staining was performed in tubes, FC testing determined the correct ABO group and D type for 99.1 percent of 222 clinical samples, as compared to accuracies of 91.9 percent for CAT and 95.0 percent for standard tube testing. FC testing also detected 99.5 percent of clinically relevant RBC alloantibodies in 239 patient samples, as compared to 98.9 percent for CAT and 94.7 percent for LISS-IAT. Using the FC filter plate technique, 104 of 109 samples (95.4%) were correctly typed for ABO and D (the remaining five samples were read as "no type determined" due to RBC and serum testing discrepancies), and RBC alloantibodies of the IgG and IgM classes were correctly identified in 98.3 percent of samples. CONCLUSIONS: Optimized FC testing methods that are comparable in accuracy to standard CAT and tube methods are described. When used with filter plates, this methodology should allow rapid and cost-effective immunohematology testing of both patient and donor samples in an automated workstation format. The same workstation should support automation of other pretransfusion assays that can be analyzed by FC.

ABO Blood-Group System↗
PubMed2003

Islet transplantation, stem cells, and transfusion medicine.

Despite the widespread use of exogenous insulin, morbidity and mortality caused by type 1 diabetes mellitus (DM) continue to place a significant burden on society, both in terms of human suffering and cost. The transplantation of vascularized pancreas, usually performed concurrently with renal transplantation, can cure type 1 DM, as shown by results in more than 15000 such transplants over about 30 years. Transplantation of isolated pancreatic islets, instead of the whole organ, however, offers an attractive alternative that minimizes surgery and its complications. Although islet transplantation initially met with only modest success (only about 9% insulin independence at 1 year posttransplant), recent changes in patient selection criteria, number and treatment of islets transplanted, and better immunosuppressive regimens dramatically improved the results; spawning widespread enthusiasm for islet transplantation. Despite this promise, organ/islet availability remains an important limitation to this technology. A solution to the problem of limited materials for transplantation may be in the use of stem/progenitor cells. This article reviews the background of the current enthusiasm for pancreatic islet cell transplantation, highlights future research trends in the field, and suggests that the new islet-related cellular therapies belong within the domain of transfusion medicine.

Cell Culture Techniques↗