title: Reactive Oxygen Species Limit the Ability of Bone Marrow Stromal Cells to Support Hematopoietic Reconstitution in Aging Mice.
abstract: Aging of organ and abnormal tissue regeneration are recurrent problems in physiological and pathophysiological conditions. This is most crucial in case of high-turnover tissues, like bone marrow (BM). Using reciprocal transplantation experiments in mouse, we have shown that self-renewal potential of hematopoietic stem and progenitor cells (HSPCs) and BM cellularity are markedly influenced with the age of the recipient mice rather than donor mice. Moreover, accumulation of excessive reactive oxygen species (ROS) in BM stromal cells compared to HSPC compartment, in time-dependent manner, suggests that oxidative stress is involved in suppression of BM cellularity by affecting microenvironment in aged mice. Treatment of these mice with a polyphenolic antioxidant curcumin is found to partially quench ROS, thereby rescues stromal cells from oxidative stress-dependent cellular injury. This rejuvenation of stromal cells significantly improves hematopoietic reconstitution in 18-month-old mice compared to age control mice. In conclusion, this study implicates the role of ROS in perturbation of stromal cell function upon aging, which in turn affects BM's reconstitution ability in aged mice. Thus, a rejuvenation therapy using curcumin, before HSPC transplantation, is found to be an efficient strategy for successful marrow reconstitution in older mice.
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology , New Delhi, India .
authors.forename: Rahul
authors.initials: R
authors.lastname: Khatri
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology , New Delhi, India .
authors.forename: Shyam
authors.initials: S
authors.lastname: Krishnan
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology , New Delhi, India .
authors.forename: Sushmita
authors.initials: S
authors.lastname: Roy
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology , New Delhi, India .
authors.forename: Saborni
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology , New Delhi, India .
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Stem Cell Biology Laboratory, National Institute of Immunology , New Delhi, India .
authors.forename: Asok
authors.initials: A
authors.lastname: Mukhopadhyay
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects; D003114:Colony-Forming Units Assay; D003474:Curcumin / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D003474:Curcumin; D000111:Acetylcysteine