A critical role of SDF-1/CXCR4 for MSC trafficking and anti-inflammatory functions. (A) GFP-positive cells were detected in the submandibular glands of NOD/Ltj mice but not in control mice 1 week after allogeneic GFP-labeled BMMSC infusion. (B) ELISA (n = 6) showed that SDF-1 was significantly higher in serum ($P = .001), salivary gland ($P = 1.287 × 10−7), spleen ($P = .0002), and lymph nodes homogenates ($P = .0004) of NOD/Ltj mice than in control mice. In NOD/Ltj, the concentration of SDF-1 in salivary gland was the highest (*all P < .05), and in ICR mice bone marrow contained the highest SDF-1 (#all P < .05). (C) Real-time PCR for Cxcr4 expression in mice BMMSCs. The level of BMMSCs Cxcr4 gene from NOD/Ltj mice of 0.082 ± 0.043 was ∼ 5-fold lower than that from ICR, BALB/c, or C57BL/6-gfp mice (*all P < .05, n = 9). (D) Real-time PCR for CXCR4 expression in human BMMSCs. The level of BMMSCs CXCR4 gene from SS patients was ∼ 8-fold lower than that from healthy people (P = .009, n = 7). (E) In NOD/Ltj mice, higher numbers of GFP+ BMMSCs were detected in salivary glands after C57BL/6-gfp MSC infusion (MSCT NOD) compared with the CXCR4-blocked C57BL/6-gfp BMMSCs group (C-b MSCT NOD) 1 week after transplantation (P = 4.5 × 10−9, n = 12). A similar trend was observed for GFP+ BMMSCs in spleen, bone marrow, and lymph node in both NOD/Ltj and ICR mice (*all P < .05, n = 12). (F) Salivary flow rate (n = 6) of CXCR4-blocked BALB/c BMMSC-treated NOD/Ltj mice was significantly lower than mice in the normal BALB/c BMMSC infusion group (*P = .044 at 17 weeks and P = .036 at 18 weeks) and were similar to the untreated control group (#P = .475 at 17 weeks and P = .522 at 18 weeks).
