title: DHP-derivative and low oxygen tension effectively induces human adipose stromal cell reprogramming.
abstract: METHODS
  In this study, we utilized a combination of low oxygen tension and a novel anti-oxidant, 4-(3,4-dihydroxy-phenyl)-derivative (DHP-d) to directly induce adipose tissue stromal cells (ATSC) to de-differentiate into more primitive stem cells. De-differentiated ATSCs was overexpress stemness genes, Rex-1, Oct-4, Sox-2, and Nanog. Additionally, demethylation of the regulatory regions of Rex-1, stemnesses, and HIF1alpha and scavenging of reactive oxygen species were finally resulted in an improved stem cell behavior of de-differentiate ATSC (de-ATSC). Proliferation activity of ATSCs after dedifferentiation was induced by REX1, Oct4, and JAK/STAT3 directly or indirectly. De-ATSCs showed increased migration activity that mediated by P38/JUNK and ERK phosphorylation. Moreover, regenerative efficacy of de-ATSC engrafted spinal cord-injured rats and chemical-induced diabetes animals were significantly restored their functions.
  
  
  CONCLUSIONS
  Our stem cell remodeling system may provide a good model which would provide insight into the molecular mechanisms underlying ATSC proliferation and transdifferentiation. Also, these multipotent stem cells can be harvested may provide us with a valuable reservoir of primitive and autologous stem cells for use in a broad spectrum of regenerative cell-based disease therapy.
authors.affiliation: Department of Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
authors.forename: Min Ki
authors.initials: MK
authors.lastname: Jee
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Kim
authors.forename: Yong Man
authors.initials: YM
authors.lastname: Han
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Jung
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Kang
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Kim
authors.forename: Soo Kyung
authors.initials: SK
authors.lastname: Kang
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D015153:Blotting, Western; D002396:Catechols / Q000494:pharmacology*; D054337:Cell Dedifferentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D054338:Cell Transdifferentiation / Q000187:drug effects; D017690:Cell Transplantation / Q000379:methods; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000601:surgery; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010100:Oxygen / Q000494:pharmacology*; D000084682:Phellinus; D010936:Plant Extracts; D011134:Polysaccharides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013119:Spinal Cord Injuries / Q000601:surgery; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation
chemical_list: D002396:Catechols; C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen