Article

Microchimerism in Salivary Glands after Blood- and Marrow-Derived Stem Cell Transplantation

Faculty of Dentistry, McGill University, Montreal, Canada.
Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation (Impact Factor: 3.35). 10/2010; 17(3):429-33. DOI: 10.1016/j.bbmt.2010.09.021
Source: PubMed

ABSTRACT Blood- and marrow-derived stem cells (BMDSCs) provide disease-ameliorating effects for cardiovascular and autoimmune diseases. Microchimerism from donor BMDSCs has been reported in several recipient tissues. We hypothesized that this finding suggests a potential use of BMDSCs in the treatment of salivary dysfunctions. We investigated the presence of Y chromosome-positive cells in salivary gland biopsies of 5 females who had received a marrow or blood stem cell transplant from male donors. One to 16 years after transplantation, all recipients exhibited scattered Y chromosome-positive cells in the acini, ducts, and stroma of their salivary glands (mean of 1.01%). Potentially, these cells can be markers of transplantation tolerance, contribute to neoplastic epithelial tissues, or engraft at sites of injury. In addition, transplantation of BMDSCs could be used for treatment of Sjögren's syndrome and salivary glands damaged by therapeutic irradiation for cancers of the head and neck.

Full-text

Available from: Yoshinori Sumita, Jun 14, 2015
0 Followers
 · 
133 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Transplantations of bone marrow-derived cells (BMDCs) are traditionally used for hematologic diseases, but there are increasing numbers of clinical trials using BMDC treatments for non-hematologic disorders, including autoimmune diseases. BMDCs are recently reported to improve organ functions. This paper will review available reports supporting the role of BMDCs in reducing xerostomia (i.e. re-establishing salivary gland functions) due to head and neck irradiation for cancer therapies and in Sjögren's syndrome. There are reports that BMDCs provide a beneficial effect on the saliva production. BMDCs positively affect blood vessels stability and regeneration in irradiated salivary glands. Also, BMDCs provide an immunomodulatory activity in mice with Sjögren's-like disease. While the exact mechanisms by which BMDCs improve organ functions remain controversial, there is preliminary evidence that a combination of them (such as cell transdifferentiation, vasculogenesis, and paracrine effect) occur in salivary glands.
    The international journal of biochemistry & cell biology 10/2010; 43(1):5-9. DOI:10.1016/j.biocel.2010.10.010 · 4.24 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are reports that bone marrow cell (BM) transplants repaired irradiated salivary glands (SGs) and re-established saliva secretion. However, the mechanisms of action behind these reports have not been elucidated. To test if a paracrine mechanism was the main effect behind this reported improvement in salivary organ function, whole BM cells were lysed and its soluble intracellular contents (termed as "BM Soup") injected into mice with irradiation-injured SGs. The hypothesis was that BM Soup would protect salivary cells, increase tissue neovascularization, function, and regeneration. Two minor aims were also tested a) comparing two routes of delivering BM Soup, intravenous (I.V.) versus intra-glandular injections, and b) comparing the age of the BM Soup's donors. The treatment-comparison group consisted of irradiated mice receiving injections of living whole BM cells. Control mice received irradiation and injections of saline or sham-irradiation. All mice were followed for 8 weeks post-irradiation. BM Soup restored salivary flow rates to normal levels, protected salivary acinar, ductal, myoepithelial, and progenitor cells, increased cell proliferation and blood vessels, and up-regulated expression of tissue remodeling/repair/regenerative genes (MMP2, CyclinD1, BMP7, EGF, NGF). BM Soup was as an efficient therapeutic agent as injections of live BM cells. Both intra-glandular or I.V. injections of BM Soup, and from both young and older mouse donors were as effective in repairing irradiated SGs. The intra-glandular route reduced injection frequency/dosage by four-fold. BM Soup, which contains only the cell by-products, can be advantageously used to repair irradiation-damaged SGs rather than transplanting whole live BM cells which carry the risk of differentiating into unwanted/tumorigenic cell types in SGs.
    PLoS ONE 04/2013; 8(4):e61632. DOI:10.1371/journal.pone.0061632 · 3.53 Impact Factor