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  1. Fulltext Therapeutic effects of menstrual blood-derived endometrial stem cells on mouse models of streptozotocin-induced type 1 diabetes
    Sun YL, Shang LR, Liu RH, Li XY, Zhang SH, Ren YK, et al.
    World J Stem Cells, 2022 Jan 26;14(1):104-116.
    PMID: 35126831 DOI: 10.4252/wjsc.v14.i1.104
    BACKGROUND: Type 1 diabetes (T1D), a chronic metabolic and autoimmune disease, seriously endangers human health. In recent years, mesenchymal stem cell (MSC) transplantation has become an effective treatment for diabetes. Menstrual blood-derived endometrial stem cells (MenSC), a novel MSC type derived from the decidual endometrium during menstruation, are expected to become promising seeding cells for diabetes treatment because of their noninvasive collection procedure, high proliferation rate and high immunomodulation capacity.

    AIM: To comprehensively compare the effects of MenSC and umbilical cord-derived MSC (UcMSC) transplantation on T1D treatment, to further explore the potential mechanism of MSC-based therapies in T1D, and to provide support for the clinical application of MSC in diabetes treatment.

    METHODS: A conventional streptozotocin-induced T1D mouse model was established, and the effects of MenSC and UcMSC transplantation on their blood glucose and serum insulin levels were detected. The morphological and functional changes in the pancreas, liver, kidney, and spleen were analyzed by routine histological and immunohistochemical examinations. Changes in the serum cytokine levels in the model mice were assessed by protein arrays. The expression of target proteins related to pancreatic regeneration and apoptosis was examined by western blot.

    RESULTS: MenSC and UcMSC transplantation significantly improved the blood glucose and serum insulin levels in T1D model mice. Immunofluorescence analysis revealed that the numbers of insulin+ and CD31+ cells in the pancreas were significantly increased in MSC-treated mice compared with control mice. Subsequent western blot analysis also showed that vascular endothelial growth factor (VEGF), Bcl2, Bcl-xL and Proliferating cell nuclear antigen in pancreatic tissue was significantly upregulated in MSC-treated mice compared with control mice. Additionally, protein arrays indicated that MenSC and UcMSC transplantation significantly downregulated the serum levels of interferon γ and tumor necrosis factor α and upregulated the serum levels of interleukin-6 and VEGF in the model mice. Additionally, histological and immunohistochemical analyses revealed that MSC transplantation systematically improved the morphologies and functions of the liver, kidney, and spleen in T1D model mice.

    CONCLUSION: MenSC transplantation significantly improves the symptoms in T1D model mice and exerts protective effects on their main organs. Moreover, MSC-mediated angiogenesis, antiapoptotic effects and immunomodulation likely contribute to the above improvements. Thus, MenSC are expected to become promising seeding cells for clinical diabetes treatment due to their advantages mentioned above.

  2. Fulltext Microbiota organization is a distinct feature of proximal colorectal cancers
    Dejea CM, Wick EC, Hechenbleikner EM, White JR, Mark Welch JL, Rossetti BJ, et al.
    Proc Natl Acad Sci U S A, 2014 Dec 23;111(51):18321-6.
    PMID: 25489084 DOI: 10.1073/pnas.1406199111
    Environmental factors clearly affect colorectal cancer (CRC) incidence, but the mechanisms through which these factors function are unknown. One prime candidate is an altered colonic microbiota. Here we show that the mucosal microbiota organization is a critical factor associated with a subset of CRC. We identified invasive polymicrobial bacterial biofilms (bacterial aggregates), structures previously associated with nonmalignant intestinal pathology, nearly universally (89%) on right-sided tumors (13 of 15 CRCs, 4 of 4 adenomas) but on only 12% of left-sided tumors (2 of 15 CRCs, 0 of 2 adenomas). Surprisingly, patients with biofilm-positive tumors, whether cancers or adenomas, all had biofilms on their tumor-free mucosa far distant from their tumors. Bacterial biofilms were associated with diminished colonic epithelial cell E-cadherin and enhanced epithelial cell IL-6 and Stat3 activation, as well as increased crypt epithelial cell proliferation in normal colon mucosa. High-throughput sequencing revealed no consistent bacterial genus associated with tumors, regardless of biofilm status. However, principal coordinates analysis revealed that biofilm communities on paired normal mucosa, distant from the tumor itself, cluster with tumor microbiomes as opposed to biofilm-negative normal mucosa bacterial communities also from the tumor host. Colon mucosal biofilm detection may predict increased risk for development of sporadic CRC.
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