Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model.

BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Effect of panel-reactive antibody positivity on graft rejection before or after kidney transplantation.

INTRODUCTION: Because it is well known that kidney transplant recipients with preformed lymphocytotoxic antibodies against HLA antigens have increased graft rejection rates, a serological crossmatch is routinely performed before kidney transplantation. But, the presence of these antibodies is not routinely monitored after transplantation. We investigated the panel-reactive antibody (PRA) response to know whether variations before or after kidney transplantation were associated with graft rejection. METHODS: We prospectively analyzed sera from 350 renal allograft recipients from September 1998 to March 2003. Pretransplantation and posttransplantation sera at 3 or 5 weeks postoperatively were tested in PRA. Recipients were stratified into 3 groups according to their PRA levels group I, PRA = 0; group II, PRA = less than 50%, and group III, PRA = more than 50%. RESULTS: The total graft rejection rate among 350 recipients was 9.4% (n = 33). Twenty-four pretransplantation PRA-positive recipients had a graft rejection rate of 20.8% (n = 5), compared with an 8.6% (n = 28) rate among 326 pretransplantation PRA-negative recipients. Six of 24 posttransplantation PRA-positive recipients (25%) experienced a graft rejection versus 27 (8.3%) of 326 posttransplantation PRA-negative subjects. Among the pretransplantation PRA stratae, the rejection rate in group III was 25% (1 of 4) versus 20% (4 of 20) in group II and 8.6% (28 of 326) in group I (P < .05). According to the postransplantation PRA level, 37.5% (3 of 8) in group III versus 18.8% (3 of 16) in group II and 8.3% (27 of 326) in group I (P < .05) had a graft rejection. CONCLUSION: Our study suggests that the PRA response pretransplantation and in the early posttransplantation period correlates with the kidney allograft rejection rate.

Correlation between the immature characteristics of umbilical cord blood-derived mesenchymal stem cells and engraftment of hematopoietic stem cells in NOD/SCID mice.

Umbilical cord blood (UCB)-derived mesenchymal stem cells (MSC) facilitate the engraftment of human (h) hematopoietic stem cells when transplanted simultaneously in animal and human studies. However, the type of MSCs that preferentially enhance the engraftment of HSCs is unknown. Recent studies have shown that MSCs derived from a single source are heterogeneous in terms of cell size, morphology, proliferation rate, and differentiation potential. This study was designed to investigate the properties of UCB-MSCs, which influence the engraftment of hHSCs in a NOD/SCID mouse model. We categorized MSCs as being the most effective (UCB-352 MSCs) or the least effective (UCB-156 MSCs) at promoting the homing and engraftment of HSCs, and compared the characteristics of these 2 MSC populations. We observed that the 2 populations showed differences in characteristics typical of immature MSCs, and related to proliferation potential. We showed that UCB-352 MSCs, which proliferate quickly, preferentially enhanced the engraftment of HSCs in NOD/SCID mice. In addition, we observed differences in the pattern of both PODXL and Oct4 expression, and in the levels of cytokines such as SDF-1 and SCF using flow cytometry and membrane arrays. The more effective UCB-352 MSCs expressed higher levels of PODXL and Oct4, which were associated with immaturity, than did the UCB-156 MSCs. Furthermore, UCB-352 cells secreted greater levels of SDF-1 and SCF, both of which are required for hematopoiesis. We propose that the proliferation potential of UCB-MSCs, coupled with their immature characteristics, may serve as a novel standard to promote the homing and engraftment of HSCs.

[Occurrence of tertian malaria in a male patient who has never been abroad].

Malaria is estimated to have a worldwide incidence of more than 100 million clinical cases and approximately 1 million deaths per year. Korea, although previously known as an endemic area of tertian malaria (Plasmodium vivax), has been considered free from malaria as there had been no report on indigenous cases since 1984. Recently, however, we experienced an indigenous case of P. vivax infection in a young man who had never been abroad. The patient was a 23-year-old Korean soldier with 18-day history of recurrent fever and chill lasting 4 to 8 hours on alternative days since mid-July 1993. He had lived in Changwon, Kyongsangnam-do, before entering barracks located in Paju-gun, Kyonggi-do on June 1992, and had never been out of Korea. He had no history of blood transfusion nor parenteral use of drugs. The peripheral blood smears showed typical ring forms, trophozoites, and gametocytes of P. vivax, in addition to mild anemia and thrombocytopenia. After confirmation of the diagnosis, he was treated with hydroxychloroquine and primaquine. Follow-up blood smears no more revealed malaria parasites. It is not certain whether the present case is due to a resurgence of indigenous malaria or a secondary infection from introduced malaria. Whichever the source of infection the domestic occurrence of malaria cycle in Korea should be a warning sign in public health point of view.

Acute leukemias with unusual immunophenotypes.

Over a two-year period, immunophenotypic patterns of 266 acute leukemia cases were analyzed using a panel of tests including TdT, SmIg and 9 surface antigens by the immunofluorescence stains for the assessment of the incidence and grade of phenotypic ambiguity (lineage infidelity) and the possible clinical significance of unusual immunophenotypes. Immunophenotypes were classified into four groups according to the degree of ectopic antigen expression. We classified as Group A (91.7%, 244 of 266 cases) those expressing conventional pattern without ectopic antigen. Group B (3.0%, 8 of 266 cases) was defined to have at least two lineage specific markers and single ectopic antigen. Such a "low grade deviation" did not prevent a definite immunodiagnosis. Group C (4.2%, 11 of 266 cases) revealed a promiscuous coexpression of markers related to different lineages, including two cases (0.8%, 2 cases) of biphenotypic leukemia. Group D (1.1%, 3 cases) included unclassifiable immunophenotypes with no antigen or HLA-DR only expression. Both patients with biphenotypic leukemia and one patient with unclassifiable immunophenotypes failed to respond to induction chemotherapy, suggesting a poor prognosis in these patients. The incidence of acute myelogenous leukemia (AML) cases with one or more ectopic surface antigens was 10 (8.1%) of the 124 AML cases. Ectopic antigen expression was seen in 5 (4%) of the 125 B-lineage acute lymphoblastic leukemia (ALL) cases and 3 (25%) of the 12 T-ALL cases. It is concluded that nearly 95% of cases of acute leukemia cases can be diagnosed accurately with immunophenotyping alone including patients with a mild degree of deviation from expected antigenic patterns.(ABSTRACT TRUNCATED AT 250 WORDS)