DHP-derivative and Low Oxygen Tension Effectively Induces Human Adipose Stromal Cell Reprogramming

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2010 Feb 18

PMID 20161735

Citations 12

Authors

Min Ki Jee

Ji Hoon Kim

Yong Man Han

Sung Jun Jung

Kyung Sun Kang

Dong Wook Kim

Soo Kyung Kang

Affiliations

Soon will be listed here.

Abstract

Background And 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/significance: 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.

Citing Articles

An Overview of the Mechanism behind Excessive Volume of Pericardial Fat in Heart Failure.

Karna S, Kang K J Obes Metab Syndr. 2023; 32(4):322-329.

PMID: 38036419 PMC: 10786210. DOI: 10.7570/jomes23042.

Insight into Hypoxia Stemness Control.

Di Mattia M, Mauro A, Citeroni M, Dufrusine B, Peserico A, Russo V Cells. 2021; 10(8).

PMID: 34440930 PMC: 8394199. DOI: 10.3390/cells10082161.

Hypoxia Suppresses Spontaneous Mineralization and Osteogenic Differentiation of Mesenchymal Stem Cells via IGFBP3 Up-Regulation.

Kim J, Yoon S, Song S, Park S, Kim W, Park I Int J Mol Sci. 2016; 17(9).

PMID: 27563882 PMC: 5037669. DOI: 10.3390/ijms17091389.

Vitamin C promotes the proliferation of human adipose-derived stem cells via p53-p21 pathway.

Zhang P, Li J, Qi Y, Zou Y, Liu L, Tang X Organogenesis. 2016; 12(3):143-151.

PMID: 27231022 PMC: 4993295. DOI: 10.1080/15476278.2016.1194148.

Tumorigenesis: cell defense against hypoxia?.

Pakravan N Oncol Rev. 2015; 7(1):e1.

PMID: 25992222 PMC: 4419620. DOI: 10.4081/oncol.2013.e1.

References

Covello K, Kehler J, Yu H, Gordan J, Arsham A, Hu C . HIF-2alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev. 2006; 20(5):557-70. PMC: 1410808. DOI: 10.1101/gad.1399906. View

Warnecke P, Stirzaker C, Song J, Grunau C, Melki J, Clark S . Identification and resolution of artifacts in bisulfite sequencing. Methods. 2002; 27(2):101-7. DOI: 10.1016/s1046-2023(02)00060-9. View

Rosen G, Press D, SHERMAN G, Galaburda A . The development of induced cerebrocortical microgyria in the rat. J Neuropathol Exp Neurol. 1992; 51(6):601-11. DOI: 10.1097/00005072-199211000-00005. View

Alves J, Barone P, Engelender S, Froes M, Menezes J . Initial stages of radial glia astrocytic transformation in the early postnatal anterior subventricular zone. J Neurobiol. 2002; 52(3):251-65. DOI: 10.1002/neu.10087. View

Huttmann K, Sadgrove M, Wallraff A, Hinterkeuser S, Kirchhoff F, Steinhauser C . Seizures preferentially stimulate proliferation of radial glia-like astrocytes in the adult dentate gyrus: functional and immunocytochemical analysis. Eur J Neurosci. 2003; 18(10):2769-78. DOI: 10.1111/j.1460-9568.2003.03002.x. View

Grafi G, Ben-Meir H, Avivi Y, Moshe M, Dahan Y, Zemach A . Histone methylation controls telomerase-independent telomere lengthening in cells undergoing dedifferentiation. Dev Biol. 2007; 306(2):838-46. DOI: 10.1016/j.ydbio.2007.03.023. View

Kang S, Putnam L, Ylostalo J, Popescu I, Dufour J, Belousov A . Neurogenesis of Rhesus adipose stromal cells. J Cell Sci. 2004; 117(Pt 18):4289-99. DOI: 10.1242/jcs.01264. View

Hartfuss E, Galli R, Heins N, Gotz M . Characterization of CNS precursor subtypes and radial glia. Dev Biol. 2001; 229(1):15-30. DOI: 10.1006/dbio.2000.9962. View

Pixley S, de Vellis J . Transition between immature radial glia and mature astrocytes studied with a monoclonal antibody to vimentin. Brain Res. 1984; 317(2):201-9. DOI: 10.1016/0165-3806(84)90097-x. View

10.

Kang S, So H, Moon Y, Kim C . Proteomic analysis of injured spinal cord tissue proteins using 2-DE and MALDI-TOF MS. Proteomics. 2006; 6(9):2797-812. DOI: 10.1002/pmic.200500621. View

11.

Lennmyr F, Karlsson S, Gerwins P, Ata K, Terent A . Activation of mitogen-activated protein kinases in experimental cerebral ischemia. Acta Neurol Scand. 2002; 106(6):333-40. DOI: 10.1034/j.1600-0404.2002.01313.x. View

12.

Yaccoby S . The phenotypic plasticity of myeloma plasma cells as expressed by dedifferentiation into an immature, resilient, and apoptosis-resistant phenotype. Clin Cancer Res. 2005; 11(21):7599-606. PMC: 1592552. DOI: 10.1158/1078-0432.CCR-05-0523. View

13.

Akimoto T, Nonaka T, Harashima K, Sakurai H, Ishikawa H, Mitsuhashi N . Radicicol potentiates heat-induced cell killing in a human oesophageal cancer cell line: the Hsp90 chaperone complex as a new molecular target for enhancement of thermosensitivity. Int J Radiat Biol. 2004; 80(7):483-92. DOI: 10.1080/09553000410001725107. View

14.

Ceradini D, Kulkarni A, Callaghan M, Tepper O, Bastidas N, Kleinman M . Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat Med. 2004; 10(8):858-64. DOI: 10.1038/nm1075. View

15.

Avivi Y, Morad V, Ben-Meir H, Zhao J, Kashkush K, Tzfira T . Reorganization of specific chromosomal domains and activation of silent genes in plant cells acquiring pluripotentiality. Dev Dyn. 2004; 230(1):12-22. DOI: 10.1002/dvdy.20006. View

16.

Wagers A, Weissman I . Plasticity of adult stem cells. Cell. 2004; 116(5):639-48. DOI: 10.1016/s0092-8674(04)00208-9. View

17.

Yun Z, Maecker H, Johnson R, Giaccia A . Inhibition of PPAR gamma 2 gene expression by the HIF-1-regulated gene DEC1/Stra13: a mechanism for regulation of adipogenesis by hypoxia. Dev Cell. 2002; 2(3):331-41. DOI: 10.1016/s1534-5807(02)00131-4. View

18.

Kang S, Lee D, Bae Y, Kim H, Baik S, Jung J . Improvement of neurological deficits by intracerebral transplantation of human adipose tissue-derived stromal cells after cerebral ischemia in rats. Exp Neurol. 2003; 183(2):355-66. DOI: 10.1016/s0014-4886(03)00089-x. View

19.

Ezashi T, Das P, Roberts R . Low O2 tensions and the prevention of differentiation of hES cells. Proc Natl Acad Sci U S A. 2005; 102(13):4783-8. PMC: 554750. DOI: 10.1073/pnas.0501283102. View

20.

Goodell M . Stem-cell "plasticity": befuddled by the muddle. Curr Opin Hematol. 2003; 10(3):208-13. DOI: 10.1097/00062752-200305000-00003. View