The effects of various irradiation doses on the growth and differentiation of marrow-derived human mesenchymal stromal cells.
Mesenchymal stromal cells (MSC) are progenitors of mesenchymal tissues including bones. Irradiation can damage the osteogenic activity of human marrow by suppressing osteoblasts leading to post-irradiation osteoporosis. However, the effect of therapeutic irradiation on MSC remains unexplored. We investigated the effects of various doses of X-ray irradiation on human MSC (hMSC) by measuring its post-irradiation proliferation and differentiation activities. Standard immunophenotypes and differentiating functions of the MSC were determined. Irradiation inhibited proliferation of hMSC up to two wk post-irradiation but thereafter, those residual surviving cells regained their normal proliferation rate. Bone forming activity as reflected by alkaline phosphatase (ALP) and calcium deposition were both reduced in a dose-dependent fashion. Maximum suppressive effect on osteogenic activity was noted in MSC treated with high-dose irradiation (12 Gy). Adipocyte percentage was also reduced by 50% in cultures that received >4 Gy. Attempts to protect the irradiated cells with 1 microM all-trans retinoic acid did not show any beneficial effect on MSC proliferation and differentiation. The direct impairment of proliferation and osteogenic differentiation potential of MSC by irradiation may contribute partly to the post-transplant osteoporosis.
Li
Jing
J
Department of Paediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong.
Kwong
Dora L W
DL
Chan
Godfrey C-F
GC
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D050156:Adipogenesis / Q000528:radiation effects; D000469:Alkaline Phosphatase / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects / Q000528:radiation effects*; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects*; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007641:Keratolytic Agents / Q000494:pharmacology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D010012:Osteogenesis / Q000187:drug effects / Q000528:radiation effects; D011832:Radiation Injuries / Q000517:prevention & control; D014212:Tretinoin / Q000494:pharmacology; D014965:X-Rays
D007641:Keratolytic Agents; D014212:Tretinoin; D000469:Alkaline Phosphatase; D002118:Calcium