Method of increasing proliferation of bone marrow mononuclear cells expressing STRO1-dim

• US 10,544,394 B2
• Filed: 08/27/2014
• Issued: 01/28/2020
• Est. Priority Date: 09/24/2004
• Status: Active Grant

• Current Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Original Assignee: Mesoblast, Inc. (Mesoblast Ltd.)
• Inventors: Gronthos, Stan, Zannettino, Andrew Christopher William
• Primary Examiner(s): Wilson, Michael C
• Application Number:
  US14/470,769
• Publication Number:
  US 20150072422A1
• Time in Patent Office: 1,980 Days
• Field of Search: 424 9321, 435325
• CPC Class Codes: A61P 1/02 Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 2501/125 Stem cell factor [SCF], c-kit ligand [KL]
• CPC Class Codes: C12N 2501/135 Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 2501/22 Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 2501/2301 Interleukin-1 (IL-1)
• CPC Class Codes: C12N 2501/2303 Interleukin-3 (IL-3)
• CPC Class Codes: C12N 2501/2306 Interleukin-6 (IL-6)
• CPC Class Codes: C12N 2501/25 Tumour necrosing factors [TNF]
• CPC Class Codes: C12N 2501/999 Small molecules not provided for elsewhere
• CPC Class Codes: C12N 2502/13 connective tissue cells; generic mesenchyme cells, e.g. so-called "embryonic fibroblasts"
• CPC Class Codes: C12N 5/0652 Cells of skeletal and connective tissues; Mesenchyme
• CPC Class Codes: C12N 5/0663 : Bone marrow mesenchymal stem cells (BM-MSC)

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.

Claims

1. A method of increasing proliferation of STRO1^dim cells, the method comprising:

co-culturing;

a) greater than 5% STRO1^bright multipotent mesenchymal cells isolated from bone marrow mononuclear cells with

b) STRO1^dim cells isolated from bone marrow mononuclear cells

such that proliferation of the STRO1^dim cells is increased,

wherein;

i) the STRO1^bright multipotent mesenchymal cells comprise a plurality of cells expressing VCAM1,

ii) the STRO1^dim cells comprise more committed precursor cell types than the STRO1^bright multipotent mesenchymal cells,

iii) the STRO1^bright cells are more primitive than the STRO1^dim cells, and

iv) the STRO1^bright cells emit at least a four-fold greater fluorescent signal than STRO1^dim cells as determined by FACS analysis.

2. A method as claimed in claim 1, wherein the STRO-1^dim cells express CXCR4.