title: Conversion of adipose-derived stem cells into natural killer-like cells with anti-tumor activities in nude mice.
abstract: Efforts to develop peripheral blood-derived nature killer (NK) cells into therapeutic products have been hampered by these cells' low abundance and histoincompatibility. On the other hand, derivation of NK-like cells from more abundant cell sources such as embryonic stem cells (ESCs) and umbilical cord blood (UCB) requires the selection of rare CD34+ cells. Thus, we sought to convert adipose-derived stem cells (ADSCs), which are abundant and natively CD34+, into NK-like cells. When grown in hematopoietic induction medium, ADSCs formed sphere clusters and expressed hematopoietic markers CD34, CD45, and KDR. Further induction in NK cell-specific medium resulted in a population of cells that expressed NK cell marker CD56, and thus termed ADSC-NK. Alternatively, the hematopoietically induced ADSCs were transduced with NK cell-specific transcription factor E4BP4 prior to induction in NK cell-specific medium. This latter population of cells, termed ADSC-NKE, expressed CD56 and additional NK cell markers such as CD16, CD94, CD158, CD314, FasL, and NKp46. ADSC-NKE was as potent as NK leukemia cell NKL in killing breast cancer cell MCF7 and prostate cancer cells DU145, PC3, LnCap, DuPro, C4-2 and CWR22, but exhibited no killing activity toward normal endothelial and smooth muscle cells. In nude mice test ADSC-NKE was able to significantly delay the progression of tumors formed by MCF7 and PC3. When injected into immunocompetent rats, ADSC-NKE was detectable in bone marrow and spleen for at least 5 weeks. Together, these results suggest that ADSCs can be converted into NK-like cells with anti-tumor activities.
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Hongxiu
authors.initials: H
authors.lastname: Ning
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Hong-En
authors.initials: HE
authors.lastname: Lei
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Yong-De
authors.initials: YD
authors.lastname: Xu
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Rui-Li
authors.initials: RL
authors.lastname: Guan
authors.affiliation: Department of Medicine, School of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Venstrom
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Guiting
authors.initials: G
authors.lastname: Lin
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Tom F
authors.initials: TF
authors.lastname: Lue
authors.affiliation: Andrology Center, Peking University First Hospital, Peking University, Beijing, China.
authors.forename: Zhongcheng
authors.initials: Z
authors.lastname: Xin
authors.affiliation: Knuppe Molecular Urology Laboratory, Department of Urology, School of Medicine, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Ching-Shwun
authors.initials: CS
authors.lastname: Lin
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology*; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003470:Culture Media / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells / Q000276:immunology / Q000473:pathology; D053222:Fas Ligand Protein / Q000235:genetics / Q000276:immunology; D005260:Female; D015870:Gene Expression; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D061986:MCF-7 Cells; D008297:Male; D051379:Mice; D008819:Mice, Nude; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000235:genetics / Q000276:immunology; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D014161:Transduction, Genetic; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000276:immunology
chemical_list: D015703:Antigens, CD; D050976:Basic-Leucine Zipper Transcription Factors; D015415:Biomarkers; D003470:Culture Media; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D036341:Intercellular Signaling Peptides and Proteins; C112260:NCR1 protein, human; C497440:NFIL3 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D040301:Vascular Endothelial Growth Factor Receptor-2