The role of CD44-hyaluronic acid interaction in exogenous mesenchymal stem cells homing to rat remnant kidney.

BACKGROUND/AIMS: The aim of our study was to reveal the role of CD44-Hyaluronic acid (HA) in the homing and improving renal function of systemically transplanted MSCs in chronic renal failure. METHODS: First, a remnant kidney model was established in rats and the expression of HA was determined using immunohistochemistry (IHC) and western blotting. Next, chemotaxis assay using flow cytometry, and cell migration assay of MSCs were performed in vitro. Then, MSCs were transplanted into rats, thus, sprague-Dawley (SD) rats were randomly divided into sham group, 5/6 nephrectomy (5/6 Nx) group, MSC group and MSC/Anti-CD44 group (n = 8 for all groups). Migration of MSCs to the kidney in these rats was assessed by using cell tracking experiments, and tissue damage was evaluated by morphological analysis using Masson's trichrome staining and periodic acid Schiff staining. RESULTS: HA was significantly observed in 5/6 Nx group, but not in sham group. Meanwhile, HA was discovered induced MSCs migration remarkably (p < 0.05) and anti-CD44 antibody inhibited the migration significantly (p < 0.05) in vitro. In vivo, the GFP-MSCs were observed in MSC group and the cells reduced in MSC/Anti-CD44 groups, especially, in the tubulointerstitium. CONCLUSION: Our findings reveal that CD44-HA has the potential to induce MSCs homing to injured tissue, while its effect on the ability of MSCs, improving tissue function, is not significant.

[Effect of intrauterine hepatitis B virus infection on peripheral blood mononuclear cells interferon-gamma and interleukin-4 in newborns].

OBJECTIVE: To observe the effect of intrauterine hepatitis B virus (HBV) infection on peripheral blood mononuclear cells function of secreting interferon-gamma and interleukin-4. METHODS: Pregnant women were systematically screened for HBsAg and HBeAg when attending the antenatal clinic at the Qinhuangdao Maternal and Child Health Hospital. Totally 67 pairs of mothers and infants were enrolled into this study after obtaining the women's consent. Venous blood samples were collected from the infants within 6 hours after birth and before HBIG injection and HBVac immunization. Blood sample was taken from the mother at or after the time when the infant was born. HBV DNA in plasma and PBMC from mothers and their newborns were examined using polymerase chain reaction (PCR). According to HBV DNA in PBMC of newborns, they were divided into two groups. The PBMCs isolated from newborn were cultured with purified HBsAg or phytohemagglutinin (PHA). The supernatant interleukin-4 and interferon-gamma level was measured by using enzyme linked immunosorbent assay (ELISA). RESULTS: In 19 newborns PBMC was positive for HBV DNA. Maternal PBMC HBV DNA positivity was associated with high rate of intrauterine HBV infection in the infants (chi2 = 7.58, P < 0.01). Compared with the infants whose PBMC HBV DNA was negative, the infants with PBMC positive for HBV DNA expressed a lower level interferon-gamma secretion after purified HBsAg stimulation (t = 4.71, P < 0.01), however, no significant difference was seen after PHA stimulation (t = 1.21, P > 0.05). The supernatant IL-4 level detected after stimulation with purified HBsAg was higher in the newborns whose PBMC HBV DNA was positive as compared with those negative for PBMC HBV DNA (t = -8.51, P < 0.05). The level of IL-4 did not show any significant difference after stimulation with PHA between the PBMC HBV DNA negative and positive groups (t = -2.40, P > 0.05). CONCLUSION: Infection with HBV of maternal PBMC is responsible for perinatal newborn's PBMC HBV infection and it may be an important route of HBV vertical transmission. Infants whose mothers were positive for HBsAg, HBeAg and HBV DNA were at extraordinarily high risk for hepatitis B virus infection. PBMC infected with HBV could influence the status of humoral and cellular immunity resulting in persistent HBV infection and recurrent mother to infant transmission of HBV. Low responses of interferon-gamma and high interleukin-4 transcription upon specific stimulation exist in infants whose PBMC were positive for HBV DNA in uterus may contribute to immune tolerance to HBV.