Peripheral blood fibrocytes differentiation pathway and...

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 5/02 (2006.01) A61K 35/12 (2006.01) A61K 35/14 (2006.01) A61K 35/26 (2006.01) A61K 35/28 (2006.01) A61K 38/18 (2006.01) A61K 38/19 (2006.01) C12N 5/06 (2006.01) C12Q 1/24 (2006.01)

Patent

CA 2449466

Disclosed are the identification of a differentiation pathway of cultured fibrocytes, characterization of the signals for fibrocyte migration to wound site <i>in vivo </i>, and the potential role of fibrocytes in wound contracture. The invention relates to a method for producing fibrocytes comprising contacting a population of human peripheral blood mononuclear cells (PBMC comprising predominantly CD14+ cells with autologous T cells or a form of TGF.szlig., preferably TGF.szlig.1, thereby inducing differentiation of fibrocytes from precursors in the PBMC population. These fibrocytes are useful for treating a wound in a mammalian subject by administering fibrocytes to the subject, preferably in combination with TGF1. Also disclosed are methods for attracting or targeting fibrocytes to a wound by administering SLC or another agonist of the CCR7 chemokine receptor, at or near the site of the wound, and methods of decreasing undesired wound fibrosis by inhibiting fibrocyte activity.

L'invention concerne l'identification d'une voie de différenciation de fibrocytes cultivés, la caractérisation des signaux pour la migration des fibrocytes vers des sites lésés in vivo, et le rôle potentiel des fibrocytes dans des contractures de cicatrisation. L'invention concerne un procédé de production de fibrocytes consistant à mettre en contact une population de cellules mononucléaires sanguines périphériques humaines (PBMC) comprenant essentiellement des cellules CD14 avec des cellules T autologues ou une forme de TGF.beta., de préférence TGF.beta.¿1?, avec induction permettant de différencier des fibrocytes des précurseurs dans la population PBMC. Ces fibrocytes sont utilisés pour le traitement d'une lésion chez un sujet mammifère, par administration de fibrocytes audit sujet, de préférence en combinaison avec TGF.beta.¿1?. L'invention concerne en outre des procédés d'attraction ou de ciblage de fibrocytes sur une plaie, par administration de SLC ou d'un autre agoniste du récepteur chimiokine CCR7, ou à proximité du site de la plaie, ainsi que des procédés de réduction de fibrose lésée indésirable par inhibition d'activité fibrocyte.

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