Methods for the treatment of tissue lesions with CCR2 agonists
The present invention relates to methods and pharmaceutical compositions for the treatment of tissue lesions. The inventors showed that CCR2 is expressed on FMCs, especially on a subpopulation of progenitor cells, that they call “fetal myeloid progenitor cells” (FMPCs), and mediates the recruitment of these cells to maternal wound tissue. Moreover, the inventors reported that recruited FMCs/FMPCs improve maternal skin wound healing by organizing blood vessel endothelium and secreting pro-angiogenesis peptides, particularly chemokine CXCL1, to enhance angiogenesis in wound. In particular, the present invention relates to CCR2 agonists for use in the treatment of tissue lesions in a subject in need thereof.
1. A method of treating a tissue lesion in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a CCR2 agonist,
wherein the subject is a female who is pregnant or has been pregnant at least one time,
wherein the CCR2 agonist comprises a polypeptide having the identity of SEQ ID NO:3, and
wherein the therapeutically effective amount of the CCR2 agonist is sufficient to mediate recruitment of fetal myeloid progenitor cells (FMPCs) from blood circulation to the tissue lesion.
2. The method of claim 1 wherein the CCR2 agonist comprising the polypeptide is an immunoadhesin.
3. The method according to claim 1 , wherein the tissue lesion is selected from the group consisting of skin lesion, hepatic lesion, cardiac lesion, lung lesion, neurologic lesion, ocular lesion, stomach lesion, pancreas lesion, spleen lesion, bowel lesion, thyroid lesion, thymus lesion, kidney lesion, artery lesion, vein lesion, bone lesion, bone marrow lesion, muscle lesion, tendon lesion, ligament lesion, reproductive organs lesion and endocrine glands lesion.
4. The method according to claim 1 , wherein the tissue lesion is a diabetic foot ulcer resulting from diabetes.
5. The method according to claim 1 , wherein the tissue lesion is a leg ulcer resulting from sickle-cell anemia.
6. The method according to claim 1 , wherein a conventional treatment of tissue lesions is also administered to the subject.
7. A method of treating a tissue lesion in a female subject in need thereof, wherein the female subject is pregnant or has been pregnant at least one time, comprising the step of
administering to the female subject a therapeutically effective amount of a CCR2 agonist comprising a polypeptide having the amino acid sequence identity of SEQ ID NO:3,
wherein the therapeutically effective amount of the CCR2 agonist is sufficient to
recruit fetal myeloid progenitor cells (FMPCs) from blood circulation to the tissue lesion, and
promote neovascularization in the tissue lesion.
8. The method according to claim 7 , wherein the tissue lesion is selected from the group consisting of skin lesion, hepatic lesion, cardiac lesion, lung lesion, neurologic lesion, ocular lesion, stomach lesion, pancreas lesion, spleen lesion, bowel lesion, thyroid lesion, thymus lesion, kidney lesion, artery lesion, vein lesion, bone lesion, bone marrow lesion, muscle lesion, tendon lesion, ligament lesion, reproductive organs lesion and endocrine glands lesion.
9. The method according to claim 7 , wherein the tissue lesion is a diabetic foot ulcer resulting from diabetes.
10. The method according to claim 7 , wherein the tissue lesion is a leg ulcer resulting from sickle-cell anemia.
11. The method according to claim 7 , wherein a conventional treatment of tissue lesions is also administered to the subject.