title: Identification of the active components in Bone Marrow Soup: a mitigator against irradiation-injury to salivary glands.
abstract: In separate studies, an extract of soluble intracellular contents from whole bone marrow cells, named "Bone Marrow (BM) Soup", was reported to either improve cardiac or salivary functions post-myocardial infarction or irradiation (IR), respectively. However, the active components in BM Soup are unknown. To demonstrate that proteins were the active ingredients, we devised a method using proteinase K followed by heating to deactivate proteins and for safe injections into mice. BM Soup and "deactivated BM Soup" were injected into mice that had their salivary glands injured with 15Gy IR. Control mice received either injections of saline or were not IR. Results at week 8 post-IR showed the 'deactivated BM Soup' was no better than injections of saline, while injections of native BM Soup restored saliva flow, protected salivary cells and blood vessels from IR-damage. Protein arrays detected several angiogenesis-related factors (CD26, FGF, HGF, MMP-8, MMP-9, OPN, PF4, SDF-1) and cytokines (IL-1ra, IL-16) in BM Soup. In conclusion, the native proteins (but not the nucleic acids, lipids or carbohydrates) were the therapeutic ingredients in BM Soup for functional salivary restoration following IR. This molecular therapy approach has clinical potential because it is theoretically less tumorigenic and immunogenic than cell therapies.
authors.affiliation: Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, QC, H3A 0C7, Canada.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Fang
authors.affiliation: School of Dentistry, University of California, Los Angeles, CA, 90095, USA.
authors.forename: Shen
authors.initials: S
authors.lastname: Hu
authors.affiliation: Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, QC, H3A 0C7, Canada.
authors.forename: Younan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Université de Montréal, Montreal, QC, H2W 1T8, Canada.
authors.forename: Vu-Hung
authors.initials: VH
authors.lastname: Quan
authors.affiliation: Department of Oncology, Medical Physics Unit, McGill University, Montreal, QC, H3G 1A4, Canada.
authors.forename: Jan
authors.initials: J
authors.lastname: Seuntjens
authors.affiliation: Craniofacial Tissue Engineering and Stem Cells Laboratory, Faculty of Dentistry, McGill University, Montreal, QC, H3A 0C7, Canada.
authors.forename: Simon D
authors.initials: SD
authors.lastname: Tran
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016207:Cytokines / Q000378:metabolism; D019286:Endopeptidase K / Q000378:metabolism; D005260:Female; D005720:Gamma Rays; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D040081:Protein Array Analysis; D012463:Saliva / Q000187:drug effects / Q000378:metabolism; D012469:Salivary Glands / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D013696:Temperature; D014357:Trypsin / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D014357:Trypsin; D019286:Endopeptidase K