title: In vitro effects of tamoxifen on adipose-derived stem cells.
abstract: In breast reconstructive procedures, adipose-derived stem cells (ASCs) that are present in clinical fat grafting isolates are considered to play the main role in improving wound healing. In patients following chemotherapy for breast cancer, poor soft tissue wound healing is a major problem. However, it is unclear if tamoxifen (TAM) as the most widely used hormonal therapeutic agent for breast cancer treatment, affects the ASCs and ultimately wound healing. This study evaluated whether TAM exposure to in vitro human ASCs modulate cellular functions. Human ASCs were isolated and treated with TAM at various concentrations. The effects of TAM on cell cycle, cell viability and proliferation rates of ASCs were examined by growth curves, MTT assay and BrdU incorporation, respectively. Annexin V and JC-1 Mitochondrial Membrane Potential assays were used to analyze ASC apoptosis rates. ASCs were cultured in derivative-specific differentiation media with or without TAM (5 uM) for 3 weeks. Adipogenic and osteogenic differentiation levels were measured by quantitative RT-PCR and histological staining. TAM has cytotoxic effects on human ASCs through apoptosis and inhibition of proliferation in dose- and time-dependent manners. TAM treatment significantly down-regulates the capacity of ASCs for adipogenic and osteogenic differentiation (p<0.05 vs. control), and inhibit the ability of the ASCs to subsequently formed cords in Matrigel. This study is the first findings to our knowledge that demonstrated that TAM inhibited ASC proliferation and multi-lineage ASC differentiation rates. These results may provide insight into the role of TAM with associated poor soft tissue wound healing and decreased fat graft survival in cancer patients receiving TAM.
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Steven
authors.initials: S
authors.lastname: Pike
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Wei
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Aaron
authors.initials: A
authors.lastname: Klinger
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Robert
authors.initials: R
authors.lastname: Jones
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Carpenter
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Spencer A
authors.initials: SA
authors.lastname: Brown
authors.affiliation: Department of Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Paul
authors.initials: P
authors.lastname: DiMuzio
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Thomas
authors.initials: T
authors.lastname: Tulenko
authors.affiliation: Department of Surgery, Cooper University Hospital, Camden, New Jersey.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000637:transplantation*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D004965:Estrogen Antagonists / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects; D013629:Tamoxifen / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects*; D014947:Wounds and Injuries / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen