Hyaluronic acid and thrombin upregulate MT1-MMP through PI3K and Rac-1 signaling and prime the homing-related responses of cord blood hematopoietic stem/progenitor cells.

Stem Cells and Development
Neeta ShirvaikarAnna Janowska-Wieczorek

Abstract

One of the hurdles of cord blood (CB) transplantation is delayed hematopoietic engraftment. Previously, we demonstrated that supernatants isolated from leukapheresis products of granulocyte-colony stimulating factor (G-CSF)-mobilized patients primed the homing of hematopoietic stem/progenitor cells (HSPC) by enhancing their chemotactic responses to stromal cell-derived factor (SDF)-1 and stimulating matrix metalloproteinases (MMPs) MMP-2 and MMP-9. Since membrane type 1 (MT1)-MMP activates proMMP-2 and localizes proteolytic activity at the leading edge of migrating cells, in this study we investigated whether MT1-MMP contributes to the priming of the homing-related responses of CB HSPC. We found that components of supernatants of leukapheresis products such as hyaluronic acid and thrombin (i) increase the secretion of proMMP-9 and transcription and protein synthesis of MT1-MMP in CB CD34(+) cells; (ii) increase the levels of active MMP-2 in co-cultures of CD34(+) cells with endothelial cells; (iii) increase the chemoinvasion across reconstituted basement membrane Matrigel of CD34(+) cells toward a low SDF-1 gradient (20 ng/mL); and (iv) activate mitogen-activated protein kinase, phosphatidylinositol 3-kinase, and Rac-1 signalin...Continue Reading

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Citations

Oct 8, 2011·Thrombosis and Haemostasis·Jolanta M Siller-MatulaBernd Jilma
Apr 13, 2012·Biochemistry Research International·Neeta ShirvaikarAnna Janowska-Wieczorek
Sep 16, 2015·Fukushima Journal of Medical Science·Hiroshi OhkawaraYasuchika Takeishi
Dec 10, 2015·Survey of Ophthalmology·Jin-Hong ChangDimitri T Azar
Apr 11, 2012·Transfusion·Anna Janowska-WieczorekMariusz Z Ratajczak
Dec 13, 2012·CNS Neuroscience & Therapeutics·Yu-Hui ZhaoYan-Fang Chen
Apr 29, 2016·Stem Cells International·Russell EmmonsMichael De Lisio
May 15, 2015·Experimental Hematology·Nicolas Pineault, Ahmad Abu-Khader
Jun 1, 2012·Cell Adhesion & Migration·Aysegul Ocal Sahin, Miranda Buitenhuis
Aug 25, 2016·Transplantation Reviews·Reza ElahimehrDianne B McKay
Mar 2, 2016·Annals of the New York Academy of Sciences·Shiri Gur-CohenTsvee Lapidot

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Methods Mentioned

BETA
leukapheresis
GTPases
electrophoresis
protein assay
X-Ray
GTPase
transfection
confocal microscopy

Software Mentioned

AlphaEaseFC

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