DHP-derivative and low oxygen tension effectively induces human adipose stromal cell reprogramming.
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.
Jee
Min Ki
MK
Department of Biotechnology, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
Kim
Ji Hoon
JH
Han
Yong Man
YM
Jung
Sung Jun
SJ
Kang
Kyung Sun
KS
Kim
Dong Wook
DW
Kang
Soo Kyung
SK
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
D002396:Catechols; C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen