title: Paracrine effects of bone marrow soup restore organ function, regeneration, and repair in salivary glands damaged by irradiation.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Faculty of Dentistry, McGill University, Montreal, Quebec City, Canada.
authors: Simon D
authors: SD
authors: Tran
authors: Younan
authors: Y
authors: Liu
authors: Dengsheng
authors: D
authors: Xia
authors: Ola M
authors: OM
authors: Maria
authors: Saeed
authors: S
authors: Khalili
authors: Renee Wan-Jou
authors: RW
authors: Wang
authors: Vu-Hung
authors: VH
authors: Quan
authors: Shen
authors: S
authors: Hu
authors: Jan
authors: J
authors: Seuntjens
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D016026:Bone Marrow Transplantation; D005260:Female; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D019899:Paracrine Communication; D011833:Radiation Injuries, Experimental / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D012038:Regeneration / Q000235:genetics; D012463:Saliva / Q000378:metabolism; D012469:Salivary Glands / Q000378:metabolism* / Q000528:radiation effects*
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