Assay utilizing multipotent adult stem cells

• US 7,838,289 B2
• Filed: 02/14/2002
• Issued: 11/23/2010
• Est. Priority Date: 02/14/2001
• Status: Active Grant

• Current Assignee: ABT Holding Company (Athersys, Inc.)
• Original Assignee: ABT Holding Company (Athersys, Inc.), Regents of The University of Minnesota (University of Minnesota)
• Inventors: Verfaillie, Catherine M., Furcht, Leo T., Reyes, Morayma
• Primary Examiner(s): LANKFORD JR, LEON B
• Application Number:
  US10/467,963
• Publication Number:
  US 20040107453A1
• Time in Patent Office: 3,204 Days
• Field of Search: None
• US Class Current: 435/372
• CPC Class Codes: A01K 2217/05 Animals comprising random inserted nucleic acids (transgenic)
• CPC Class Codes: A01K 2217/075 inducing loss of function, i.e. knock out
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2227/106 Primate
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A61K 35/12 Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells vaccines or medicinal preparations containing antigens or antibodies A61K39/00
• CPC Class Codes: A61K 39/001 Preparations to induce tolerance to non-self, e.g. prior to transplantation
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 1/18 for pancreatic disorders, e.g. pancreatic enzymes
• CPC Class Codes: A61P 13/10 of the bladder
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/08 for bone diseases, e.g. rachitism, Paget's disease
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 27/02 : Ophthalmic agents
• CPC Class Codes: A61P 3/00 : Drugs for disorders of the metabolism of the blood or the extracellular fluid A61P7/00
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/00 : Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/00 : Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 39/02 : Antidotes
• CPC Class Codes: A61P 41/00 : Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 : Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 : Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 : Antianaemics
• CPC Class Codes: A61P 7/08 : Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock artificial tears A61P27/04
• 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 15/873 : Techniques for producing new embryos, e.g. nuclear transfer, manipulation of totipotent cells or production of chimeric embryos
• CPC Class Codes: C12N 2501/11 : Epidermal growth factor [EGF]
• CPC Class Codes: C12N 2501/113 : Acidic fibroblast growth factor (aFGF, FGF-1)
• CPC Class Codes: C12N 2501/115 : Basic fibroblast growth factor (bFGF, FGF-2)
• CPC Class Codes: C12N 2501/117 : Keratinocyte growth factors (KGF-1, i.e. FGF-7; KGF-2, i.e. FGF-12)
• CPC Class Codes: C12N 2501/119 : Other fibroblast growth factors, e.g. FGF-4, FGF-8, FGF-10
• CPC Class Codes: C12N 2501/12 : Hepatocyte growth factor [HGF]
• CPC Class Codes: C12N 2501/135 : Platelet-derived growth factor [PDGF]
• CPC Class Codes: C12N 2501/235 : Leukemia inhibitory factor [LIF]
• CPC Class Codes: C12N 2501/237 : Oncostatin M [OSM]
• CPC Class Codes: C12N 2502/08 : cells of the nervous system
• CPC Class Codes: C12N 2502/30 : tumour cells
• CPC Class Codes: C12N 2503/00 : Use of cells in diagnostics
• CPC Class Codes: C12N 2506/03 : from non-embryonic pluripotent stem cells
• CPC Class Codes: C12N 2517/02 : Cells from transgenic animals
• CPC Class Codes: C12N 5/0607 : Non-embryonic pluripotent stem cells, e.g. MASC induced pluripotent stem cells C12N5/0696
• CPC Class Codes: C12N 5/0619 : Neurons
• CPC Class Codes: C12N 5/0622 : Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
• CPC Class Codes: C12N 5/067 : Hepatocytes

Abstract

The present invention relates generally to mammalian multipotent adult stem cells (MASC), and more specifically to methods for obtaining, maintaining and differentiating MASC to cells of multiple tissue types. Uses of MASC in the therapeutic treatment of disease are also provided.

Claims

1. A method for identifying an agent that is a differentiation factor, the method comprising:

(a) contacting (1) a desired agent with (2) isolated expanded human multipotent, non-embryonic, non-germ, cells that can differentiate into at least one cell type of each of the endodermal, ectodermal and mesodermal embryonic lineages and express telomerase; and

(b) determining whether the agent of step (a) affects differentiation of the telomerase-expressing cells into a desired differentiated progeny, where affecting differentiation indicates an agent that is a differentiation factor, wherein the telomerase-expressing cells have undergone at least 10-40 cell doublings in culture.

2. The method of claim 1 wherein the telomerase-expressing cells express oct3/4.

3. The method of claim 1, wherein differentiation is into an endodermal cell type.

4. The method of claim 1, wherein differentiation is into a mesodermal cell type.

5. The method of claim 1, wherein differentiation is into an ectodermal cell type.

6. The method of claim 1, wherein the telomerase-expressing cells have undergone greater than 40 cell doublings.

7. The method of claim 1, wherein the effect on differentiation is assayed by changes in protein expression, RNA expression, or morphology.