Method of enhancing proliferation and/or survival of mesenchymal precursor cells (MPC)

Abstract

The present invention relates to methods of enhancing proliferation and/or survival of mesenchymal precursor cells (MPC) and/or progeny derived therefrom in vitro or in vivo comprising exposing the MPC or progeny to SDF-1 or analog thereof. The invention also relates to compositions comprising isolated MPCs or progeny derived therefrom and SDF-1 or analogues thereof. The present invention also relates to using such methods and compositions for ex vivo or in vivo bone formation in mammals.

1 - 53 . (canceled) 
     
     
         54 . A method of enhancing proliferation and/or survival of mesenchymal precursor cells (MPC) in vitro, the method comprising enhancing expression of SDF-1 in the MPC. 
     
     
         55 . A method as claimed in  claim 54  wherein the MPC are positive for at least one marker selected from the group consisting of STRO-1 bright , VCAM-1 bright , THY-1 bright , CD146 bright  and STRO-2 bright . 
     
     
         56 . A method as claimed in  claim 54  wherein the MPC carry at least two markers selected from the group of surface markers specific for mesenchymal precursor cells consisting of STRO-1 bri , LFA-3, THY-1, VCAM-1, ICAM-1, PECAM-1, P-selectin, L-selectin, CD49a/CD49b/CD29, CD49c/CD29, CD49d/CD29, CD29, CD18, CD61, beta-1 integrin, 6-19, thrombomodulin, CD10, CD13, SCF, PDGF-R, EGF-R, IGF1-R, NGF-R, FGF-R, Leptin-R, RANKL and CD146 or any combination of these markers. 
     
     
         57 . A method as claimed in  claim 54  wherein the MPC are negative for at least one marker selected from the group consisting of CBFA-1, collagen type II, PPARγ2, and glycophorin A. 
     
     
         58 . A method as claimed in  claim 54  wherein the MPC constitute at least 1% of the total cells of a cell composition. 
     
     
         59 . A method as claimed in  claim 54  wherein the genomes of the MPC is modified to enhance expression of SDF-1. 
     
     
         60 . A method as claimed in  claim 54  wherein the MPC are derived from a tissue selected from the group consisting of bone marrow, dental pulp cells, adipose tissue, skin, teeth, dental pulp, liver, kidney, heart, retina, brain, hair follicles, intestine, lung, spleen, lymph node, thymus, pancreas, bone, ligament, tendon and skeletal muscle. 
     
     
         61 . A method of enhancing proliferation and/or survival of mesenchymal precursor cells (MPC) progeny in vitro, the method comprising increasing exposure of the MPC progeny to SDF-1 or an analog thereof. 
     
     
         62 . A method as claimed in  claim 61  wherein the SDF-1 analog is a ligand that activates CXCR4 signalling. 
     
     
         63 . A method as claimed in  claim 62  wherein the SDF-1 analog is selected from the group consisting of the HIV-1 coat protein gp120, AMD3100 and ALX40-4C. 
     
     
         64 . A method as claimed in  claim 54  or  claim 61  wherein the MPC or MPC progeny are exposed to an exogenous stimulatory factor selected from the group consisting of platelet derived growth factor (PDGF), stem cell factor (SCF), fit 3 ligand (FL), granulocyte colony-stimulating factor (G-CSF), interleukin-3 (IL-3), interleukin-6 (IL-6), 1α,25-dihydroxyvitamin D3 (1,25D), tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β).