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Means and methods for the recruitment and identification of stem cells

a stem cell and recruitment method technology, applied in the field of biotechnology, can solve the problems of incomplete identification of the important retention signal involved in keeping stem/progenitor cells in their quiescent niche, and achieve the effect of inhibiting stem cell recruitment, increasing engrafting and isolation of multipotent stem cells

Inactive Publication Date: 2010-07-15
VLAAMS INTERUNIVERSITAIR INST VOOR BIOTECHNOLOGIE VZW +1
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Benefits of technology

The patent text discusses the role of plasmin in the body's ability to mobilize stem cells, specifically hematopoietic and endothelial progenitor cells. The text explains that molecules that increase plasmin activation or activity can be used to stimulate stem cell mobilization, while molecules that inhibit plasmin can be used to prevent stem cell mobilization. The text also mentions the discovery of a novel retention signal for stem cells called uPA receptor (uPAR), which is cleaved during plasmin-mediated mobilization to release stem cells from their niche. The cleved soluble fragments of uPAR are also endowed with capacity to stimulate stem cell mobilization. Overall, the patent text provides a technical solution for increasing stem cell engraftment and isolation.

Problems solved by technology

In addition, the identification of the important retention signals involved in keeping the stem / progenitor cells in their quiescent niche, remains incomplete.

Method used

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  • Means and methods for the recruitment and identification of stem cells
  • Means and methods for the recruitment and identification of stem cells
  • Means and methods for the recruitment and identification of stem cells

Examples

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examples

1. Loss or Inhibition of Plasmin Reduces Stem / Progenitor Cell Mobilization

[0086]To study the role of the plasminogen proteinase system with its plasminogen activators tPA and uPA, and active plasmin in stem / progenitor cell mobilization, mice lacking plasminogen (Plg− / −), tPA (tPA− / −), uPA (uPA− / −) and both activators (tPA− / −uPA− / −) were used.(17, 18) Age- and sex-matched mice were kept in IVC cages. Mobilization was induced either via a single sublethal injection i.v. of the myeloablative agent 5-fluorouracil (5-FU, 200-250 mg / kg), or via administration s.c. of recombinant human G-CSF (Filgrastim, Amgen, 200 μg / kg / d) for five consecutive days.(12) Peripheral blood (PB) samples were obtained by retro-orbital bleeding under light anesthesia. Full blood counts were determined on the Abbott Cell Dyn 1300 hemocytometer. The number of mobilized hematopoietic progenitor cells (HPCs) in the circulation was determined via methylcellulose-based CFU-C assays (MethoCult, Stem Cell Technologies)...

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Abstract

Described are methods of modulating stem / progenitor cell recruitment involving molecules that agonize the formation of plasmin stimulating the recruitment of stem / progenitor cells, including hematopoietic and endothelial precursor cells. Conversely, antagonists of plasmin can inhibit recruitment of the stem cells. In addition, the identification of the uPA receptor (uPAR) as a retention signal for stem cells in their niche suggests a novel method for increased engraftment and isolation of multipotent stem cells.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This patent application is a divisional of co-pending U.S. patent application Ser. No. 11 / 390,931, filed Mar. 28, 2006, U.S. patent, which application is a continuation of PCT International Patent Application No. PCT / EP2004 / 052432, filed on Oct. 4, 2004, designating the United States of America, and published, in English, as PCT International Publication No. WO 2005 / 032572 A2 on Apr. 14, 2005, and claims priority to European Patent Application No. 03103675.9 filed on Oct. 3, 2003, the contents of the entirety of each of which are incorporated herein by this reference.TECHNICAL FIELD[0002]The present invention relates generally to biotechnology, and more particularly to new methods of modulating stem cell and / or progenitor cell recruitment.BACKGROUND[0003]Stem cells include both embryonic and adult stem cells. Adult stems cells include, but are not limited to, hematopoietic stem cells, endothelial stem cells, neural stem cells, muscle stem...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/395A61K38/36A61P35/00A61P35/02A61K31/203A61K31/60A61K38/16A61K38/17A61K38/18A61K38/19A61K38/43A61K38/48A61K38/49A61K38/51A61K38/55A61K39/00
CPCA61K31/203A61K31/60A61K38/49A61K38/484A61K38/45A61K38/193A61K38/177A61K31/737A61K31/727A61K31/726A61K2300/00A61P35/00A61P35/02A61P7/00
Inventor CARMELIET, PETERTJWA, MARC
Owner VLAAMS INTERUNIVERSITAIR INST VOOR BIOTECHNOLOGIE VZW
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