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Essais et imagerie cellulaires

Essais cellulaires en formats 2D et 3D sur un large éventail de types de cellules primaires humaines
Nos tests ont fourni des données à l'appui d'une série d'indications thérapeutiques différentes allant du diabète à la fibrose et à l'oncologie, mais notre objectif principal reste la recherche sur les maladies anti-inflammatoires et auto-immunes. Notre approche personnalisée permet de développer des tests adaptés aux besoins spécifiques de votre programme. Outre le développement d'essais, l'étendue de nos plateformes analytiques nous permet d'offrir une gamme complète de critères d'évaluation, y compris la libération de médiateurs/cytokines, les changements dans l'expression génétique, l'ICC et l'imagerie cellulaire à haut contenu.

Essais cellulaires adaptés à votre programme

Exemples de types de cellules utilisées pour le développement de l'essai


  • Cellules sanguines : PBMC, monocytes, lymphocytes, neutrophiles, macrophages dérivés de monocytes
  • Cellules de la peau : kératinocytes, fibroblastes
  • Cellules pulmonaires : cellules épithéliales bronchiques, macrophages alvéolaires, cellules alvéolaires de type II, cellules musculaires lisses, cellules épithéliales tumorales, fibroblastes associés au cancer
  • Cellules hépatiques : hépatocytes, cellules de Kupffer, cellules stellaires
  • Autres types de cellules : îlots pancréatiques, fibroblastes synoviaux

Formats de la culture


  • 2D
    • plaques multipuits
    • transpuits
  • 3D
    • interface air-liquide
    • avec ou sans matrice
    • simple ou co-culture

Essais cellulaires et types d'effets


  • Libération de cytokines
  • Viabilité/prolifération cellulaire
  • Apoptose
  • Changements dans l'expression des gènes
  • Activité/libération enzymatique
  • Perméabilité de la barrière
  • Migration cellulaire
  • ICC
  • Immunofluorescence multiplex/imagerie cellulaire à haut contenu
  • Western blotting automatisé (Jess™)

TYPE(S) DE CELLULEEXEMPLES D'ASSAISONNEMENT

Sang total

Inhibition de la libération de TNFα et d'IL-6 stimulée par le LPS

Stimulation (PHA) et inhibition (CsA) de la prolifération cellulaire

PBMCs

Inhibition de la libération d'IL-2 et d'IFNγ stimulée par OKT3 (CD3)

Inhibition de la libération de TNFα stimulée par CD3:CD28

Monocytes et macrophages dérivés des monocytes

Inhibition de la libération de TNFα stimulée par le LPS

Lymphocytes

Inhibition de la libération d'IL-2 stimulée par OKT3 (CD3)

Neutrophiles

Transmigration (+HUVEC)

Libération de superoxyde

HUVECs

Inhibition de la libération d'IL-8 et de MCP-1 stimulée par la thrombine

Hépatocytes

Inhibition de la libération d'IL-6 et d'IL-8 stimulée par le TNFα Induction de CYP (ARNm)

Stellates

Changements induits par le TGF-β1 dans l'expression des gènes fibrogènes et le dépôt de collagène

Macrophages alvéolaires

Inhibition de la libération de TNFα stimulée par le LPS

Kératinocytes

Stimulation (IL-4) et inhibition (CsA) de la prolifération cellulaire

Fibroblastes synoviaux (RA)

Essai validé pour le criblage de nouveaux anticorps thérapeutiques anti-TNFα (biosimilaires)

Whole blood

Inhibition of LPS stimulated TNFα and IL-6 release

Stimulation (PHA) and inhibition (CsA) of cell proliferation

PBMCs

Inhibition of OKT3 (CD3) stimulated IL-2 and IFNγ release

Inhibition of CD3:CD28 stimulated TNFα release

Monocytes & Monocyte-derived Macrophages

Inhibition of LPS stimulated TNFα release

Lymphocytes

Inhibition of OKT3 (CD3) stimulated IL-2 release

Neutrophils

Transmigration (+HUVEC)

Superoxide release

HUVECs

Inhibition of thrombin stimulated IL-8 and MCP-1 release

Hepatocytes

Inhibition of TNFα stimulated IL-6 and IL-8 release CYP induction (mRNA)

Stellates

TGF-β1-induced changes in fibrogenic gene expression and collagen deposition

Alveolar macrophages

Inhibition of LPS stimulated TNFα release

Keratinocytes

Stimulation (IL-4) and inhibition (CsA) of cell proliferation

Synovial fibroblasts (RA)

Validated assay for screening novel anti-TNFα therapeutic antibodies (biosimilars)

Étude de cas : validation d'un essai biologique à l'appui d'une demande d'autorisation de mise sur le marché auprès de l'EMA

Détails :

  • Essai 2D
  • Fibroblastes synoviaux provenant de donneurs atteints de polyarthrite rhumatoïde

Développement de l'essai inclus :

  • Inhibiteur standard de référence
  • Titrage du stimulus
  • Sélection du marqueur sentinelle
  • Effet de la formulation

La validation de l'essai comprend

  • Linéarité et gamme
  • Puissance relative
  • Parallélisme
  • la spécificité
  • Précision intra/inter-essai
  • Dépistage des biosimilaires

Precision a également réalisé un screening biosimilaire comparant la puissance relative à Humira.


Résultats

1268-IL-6-RA-syn-fibs-2

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