WO2020097440A1 - Procédés de prédiction de récupération fonctionnelle de tissu à l'aide d'exosomes circulants dérivés de cellules transplantées - Google Patents

Procédés de prédiction de récupération fonctionnelle de tissu à l'aide d'exosomes circulants dérivés de cellules transplantées Download PDF

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WO2020097440A1
WO2020097440A1 PCT/US2019/060436 US2019060436W WO2020097440A1 WO 2020097440 A1 WO2020097440 A1 WO 2020097440A1 US 2019060436 W US2019060436 W US 2019060436W WO 2020097440 A1 WO2020097440 A1 WO 2020097440A1
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mir
exosomes
cells
transplanted
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PCT/US2019/060436
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Sunjay Kaushal
Progyaparamita SAHA
Sudhish SHARMA
Prashanth VALLABHAJOSYULA
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University Of Maryland, Baltimore
The Trustees Of The University Of Pennsylvania
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/92—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving lipids, e.g. cholesterol, lipoproteins, or their receptors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/5005—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells
    • G01N33/5091—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving human or animal cells for testing the pathological state of an organism
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/32—Cardiovascular disorders
    • G01N2800/324—Coronary artery diseases, e.g. angina pectoris, myocardial infarction

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  • Health & Medical Sciences (AREA)
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  • Immunology (AREA)
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  • Urology & Nephrology (AREA)
  • Hematology (AREA)
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  • Food Science & Technology (AREA)
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  • Analytical Chemistry (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Endocrinology (AREA)
  • Biophysics (AREA)
  • Physiology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)

Abstract

Le domaine des cellules souches est gêné par l'incapacité à surveiller de manière non invasive des cellules transplantées dans un organe cible d'une manière reproductible, chronosensible et spécifique à la pathologie. On a avancé l'hypothèse que la quantification et la caractérisation de cargaison intraexosomale d'exosomes circulants spécifiques à une cellule transplantée permettraient qu'une plate-forme de surveillance fiable et non invasive reflète l'activité conditionnelle de leurs équivalents cellulaires. Pour tester cette hypothèse, on a eu recours à un modèle d'infarctus du myocarde xénogène humain-rat faisant intervenir deux types de cellules progénitrices bien étudiées : des cellules dérivées de la cardiosphère (CDC) et des cellules progénitrices cardiaques (CPC) c-kit+, dérivées du même appendice auriculaire droit d'êtres humains adultes. Pour surveiller de manière non invasive l'activité de CDC ou de CPC transplantées in vivo, des exosomes plasmatiques du receveur ont été purifiés à l'aide d'anticorps dirigés contre des molécules de surface d'antigènes des leucocytes humains (HLA) uniquement exprimées sur la surface d'exosomes humains. 7 jours après la transplantation, une augmentation de la concentration en exosomes plasmatiques spécifiques des CPC de 2,5 fois a été observée comparativement aux exosomes spécifiques des CDC. L'analyse de cheminement computationnelle n'est pas parvenue à établir une liaison entre l'ARNm cellulaire de CPC ou CDC et une récupération myocardique observée. Cependant, la récupération du myocarde était fortement liée à la cargaison en ARNmi des exosomes de CPC purifiés à partir du plasma du receveur. De plus, des cheminements mécanistes régissant la récupération du myocarde ont été identifiés vers des résultats spécifiques par les CPC transplantées. Collectivement, ces résultats démontrent le potentiel d'exosomes circulants spécifiques aux cellules progénitrices en tant que biopsie liquide qui fournit un aperçu de l'état des cellules transplantées.
PCT/US2019/060436 2018-11-09 2019-11-08 Procédés de prédiction de récupération fonctionnelle de tissu à l'aide d'exosomes circulants dérivés de cellules transplantées WO2020097440A1 (fr)

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US201862758209P 2018-11-09 2018-11-09
US62/758,209 2018-11-09

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210009935A1 (en) * 2019-07-12 2021-01-14 Hitachi, Ltd. Cell culture monitoring device and cell culture system
WO2022204045A1 (fr) * 2021-03-22 2022-09-29 Spiritus Therapeutics, Inc. Utilisations diagnostiques et thérapeutiques d'exosomes puissants purifiés contenant un cargo de signature basé sur une maladie et basé sur une thérapie

Citations (2)

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WO2014013258A1 (fr) * 2012-07-19 2014-01-23 Reneuron Limited Microparticules de cellules souches
WO2017066390A1 (fr) * 2015-10-13 2017-04-20 The Trustees Of The University Of Pennsylvania Méthodes d'utilisation d'exosomes enrichis comme plateforme pour surveiller l'état d'un organe

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2014013258A1 (fr) * 2012-07-19 2014-01-23 Reneuron Limited Microparticules de cellules souches
WO2017066390A1 (fr) * 2015-10-13 2017-04-20 The Trustees Of The University Of Pennsylvania Méthodes d'utilisation d'exosomes enrichis comme plateforme pour surveiller l'état d'un organe

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20210009935A1 (en) * 2019-07-12 2021-01-14 Hitachi, Ltd. Cell culture monitoring device and cell culture system
WO2022204045A1 (fr) * 2021-03-22 2022-09-29 Spiritus Therapeutics, Inc. Utilisations diagnostiques et thérapeutiques d'exosomes puissants purifiés contenant un cargo de signature basé sur une maladie et basé sur une thérapie

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