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Materials and methds to enhance hematopoietic stem cells engraftment procedures

A cell and blood stem technology, applied in biochemical equipment and methods, blood/immune system cells, fusion cells, etc., can solve problems such as limited results

Pending Publication Date: 2017-12-29
INDIANA UNIV RES & TECH CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Many methods have been attempted to expand the number of human hematopoietic stem and progenitor cells in isolated grafts in an ex vivo setting, but with very limited success

Method used

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  • Materials and methds to enhance hematopoietic stem cells engraftment procedures
  • Materials and methds to enhance hematopoietic stem cells engraftment procedures
  • Materials and methds to enhance hematopoietic stem cells engraftment procedures

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0098] 1.PGE 2 Increase the frequency and implantation of HSPC in the long-term population

[0099] Using a limited dilution competitive transplantation model, using CD45.2 and CD45.1 congener grafts transplanted into CD45.1 / CD45.2 heterozygous mice to prove that HSPC was exposed to PGE for a short time 2 Produce long-term enhancement of HSPC and Competitive Population Recovery Unit (CRU) frequency. Next reference Figure 1A , With carrier or dmPGE 2 The bone marrow from CD45.1 or CD45.2 mice was treated separately. CD45.1 / CD45.2 hybrid bone marrow cells were used as competitor. The limiting dilution was transplanted into CD45.1 / CD45.2 heterozygous mice irradiated with a lethal dose (1100-cGy, split dose), and the chimerism in PB was analyzed at 20 weeks. A representative flow cytometry chart (bottom panel) for detecting each cell population is shown.

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PUM

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Abstract

This disclosure is directed to the methods of enhancing hematopoietic stem cells (HSPC) and progenitor cell (HSPC) engraftment procedure. Treatment in vivo of a HSPC donor with compounds that reduce PGE2 biosynthesis or PGE2 receptor antagonists alone, or in combination with other hematopoietic mobilization agents such as AMD3100 and G-CSF, increases the circulation of available HSPCs. Compounds that reduce the cellular synthesis of PGE2 include non-steroidal anti-inflammatory compounds such as indomethacin. Treatment ex vivo of HSPC with an effective amount of PGE2 or at least one of its derivatives such as 16,16-dimethyl prostaglandin E2 (dmPGE2), promotes HSPC engraftment. Similar methods may also be used to increase viral-mediated gene transduction efficacy into HSPC.

Description

[0001] This application is a divisional application of the Chinese patent application with the application number 200980149522.5 and the invention title "Materials and methods for enhancing hematopoietic stem cell implantation". The parent application is the PCT international patent application filed on November 6, 2009. / US2009 / 063654 Application for entering the Chinese national phase. [0002] Priority claim [0003] This application claims the benefits of US Provisional Patent Application No. 61 / 112,018 filed on November 6, 2008, which is incorporated herein by reference in its entirety. [0004] Government Rights Statement [0005] Part of the development of the present invention was carried out under government funding, which came from NIH fund numbers HL069669, HL079654 and DK07519. The U.S. government has certain rights in this invention. Technical field [0006] Some aspects and embodiments disclosed herein relate to materials and methods that enhance the implantation of hema...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/86C12N5/10A61K35/14A61K35/51A61P3/00A61P7/00A61P35/02A61K35/12
CPCA61K35/14A61K35/51C12N5/0647C12N15/86C12N2501/02A61K31/395A61K31/00A61K2035/124C12N15/63A61K31/405A61K31/5415A61K38/193C12N9/0083C12Y114/99001A61K31/4035A61K31/4196A61P29/00A61P3/00A61P35/02A61P43/00A61P7/00A61P7/06A61K35/28C12N5/16A61K35/50
Inventor 路易斯·M·佩卢斯乔纳森·霍格特普拉蒂博哈·辛格
Owner INDIANA UNIV RES & TECH CORP
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