Multipotent stem cells and uses thereof

• US 10,568,911 B2
• Filed: 07/13/2017
• Issued: 02/25/2020
• Est. Priority Date: 05/03/2007
• Status: Active Grant

• Current Assignee: Brigham and Women's Hospital Incorporated
• Original Assignee: Brigham and Women's Hospital Incorporated
• Inventors: Crawford, Keith D., Southgate, Christopher
• Primary Examiner(s): Yamasaki, Robert J
• Assistant Examiner(s): Constantine, Charles Zoltan
• Application Number:
  US15/648,738
• Publication Number:
  US 20180064759A1
• Time in Patent Office: 957 Days
• Field of Search: None
• 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 35/14 Blood; Artificial blood perfluorocarbons A61K31/02; umbilical cord blood A61K35/51; haemoglobin A61K38/42
• CPC Class Codes: A61K 35/24 Mucus; Mucous glands; Bursa; Synovial fluid; Arthral fluid; Excreta; Spinal fluid saliva A61K35/38
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 2500/25 Insulin-transferrin; Insulin-transferrin-selenium
• CPC Class Codes: C12N 2500/36 Lipids
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2501/105 Insulin-like growth factors [IGF]
• CPC Class Codes: C12N 2501/11 Epidermal growth factor [EGF]
• 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 2501/155 Bone morphogenic proteins [BMP]; Osteogenins; Osteogenic factor; Bone inducing factor
• CPC Class Codes: C12N 2501/22 Colony stimulating factors (G-CSF, GM-CSF)
• CPC Class Codes: C12N 2501/2303 Interleukin-3 (IL-3)
• CPC Class Codes: C12N 2501/2306 Interleukin-6 (IL-6)
• CPC Class Codes: C12N 2501/235 Leukemia inhibitory factor [LIF]
• CPC Class Codes: C12N 2501/26 Flt-3 ligand (CD135L, flk-2 ligand)
• CPC Class Codes: C12N 2501/39 Steroid hormones
• CPC Class Codes: C12N 2501/40 : Regulators of development
• CPC Class Codes: C12N 2501/41 : Hedgehog proteins; Cyclopamine (inhibitor)
• CPC Class Codes: C12N 2501/999 : Small molecules not provided for elsewhere
• CPC Class Codes: C12N 5/0639 : Dendritic cells, e.g. Langherhans cells in the epidermis
• CPC Class Codes: C12N 5/0647 : Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: C12N 5/0653 : Adipocytes; Adipose tissue
• CPC Class Codes: C12N 5/0654 : Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth
• CPC Class Codes: C12N 5/0655 : Chondrocytes; Cartilage
• CPC Class Codes: C12N 5/0657 : Cardiomyocytes; Heart cells
• CPC Class Codes: C12N 5/0658 : Skeletal muscle cells, e.g. myocytes, myotubes, myoblasts
• CPC Class Codes: C12N 5/0661 : Smooth muscle cells
• CPC Class Codes: C12N 5/0662 : Stem cells
• CPC Class Codes: C12N 5/0668 : Mesenchymal stem cells from other natural sources
• CPC Class Codes: C12N 5/067 : Hepatocytes
• CPC Class Codes: C12N 5/0676 : Pancreatic cells

Abstract

The invention provides a quiescent stem cell having the capacity to differentiate into ectoderm, mesoderm and endoderm, and which does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105, CD90, CD66A, CD66E, CXCR4, CD133 or an SSEA. The invention further provides a proliferative stem cell, which expresses genes including Oct-4, Nanog, Sox2, GDF3, P16INK4, BMI, Notch, HDAC4, TERT, Rex-1, TWIST, KLF-4 and Stella but does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105, CD90, CD66A, CD66E, CXCF4, CD133 or an SSEA. The cells of the invention can be isolated from adult mammals, have embryonic cell characteristics, and can form embryoid bodies. Methods for obtaining the stem cells, as well as methods of treating diseases and differentiating the stem cells, are also provided.

Claims

1. A method of enhancing recovery from joint surgery, comprising administering to the joint during surgery to repair the joint a composition comprising stem or progenitor cells that express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD13, CD44, CD45, and CD90 in an amount effective to enhance recovery, and a pharmaceutically acceptable carrier.

2. The method of claim 1, wherein the stem cells are capable of proliferating and differentiating into ectoderm, mesoderm and endoderm.

3. The method of claim 1, wherein the stem cells are synovial fluid derived, blood derived or tissue derived.

4. The method of claim 1, wherein the stem cells are isolated from a mammal.

5. The method of claim 4, wherein the stem cells are isolated from a human.

6. The method of claim 4, wherein the stem cells are isolated from an adult mammal.

7. The method of claim 1, wherein the stem cells are autologous with respect to a recipient undergoing the joint surgery.

8. The method of claim 1, wherein the stem cells are allogeneic with respect to a recipient undergoing the joint surgery.

9. The method of claim 1, wherein the stem cells are committed to differentiate.

10. The method of claim 1, wherein the composition further comprises at least one subpopulation of differentiated progeny cells.

11. The method of claim 1, wherein the population of cells expresses a stem cell transcription factor selected from the group consisting of Oct-4, Nanog, Sox-2, Rex-1, GDF-3 and Stella.