Multipotent stem cells and uses thereof

Patent metadata

Field	Value
Publication number	US-2016243166-A1
Application number	US-201514862899-A
Country	US
Kind code	A1
Filing date	Sep 23, 2015
Priority date	May 3, 2007
Publication date	Aug 25, 2016
Grant date	—

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 and CD90. The invention further provides a proliferative stem cell, which expresses genes including Oct-4, Nanog, Sox2, GDF3, P16INK4, BMI, Notch, HDAC4, TERT, Rex-1 and TWIST but does not express cell surface markers including MHC class I, MHC class II, CD44, CD45, CD13, CD34, CD49c, CD73, CD105 and CD90. 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 the differentiated stem cells, are also provided.

First claim

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 in an amount effective to enhance recovery, and a pharmaceutically acceptable carrier.

2 . The method of claim 1 , wherein the stem cells express a stem cell transcription factor but do not detectably express MHC Class I or cell surface markers CD13, CD44, CD45, CD90, and CD105.

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

4 . The method of claim 2 , wherein the stem cells are synovial fluid derived, blood derived or tissue derived.

5 . The method of claim 2 , wherein the stem cells are isolated from a mammal.

6 . The method of claim 4 , wherein the stem cell is isolated from a human.

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

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

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

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

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

12 . The method of claim 11 , further comprising at least one subpopulation of differentiated immune cells.

13 . A method of differentiating a stem or progenitor cell, the method comprising: culturing a stem or progenitor cell that expresses a stem cell transcription factor but does not detectably express MHC Class I or cell surface markers CD13, CD44, CD45 and CD90, under conditions to form a desired cell type, thereby differentiating the stem or progenitor cell.

14 . The method of claim 13 , wherein the stem or progenitor cell is synovial fluid derived, blood derived or tissue derived.

15 . The method of claim 13 , wherein the stem or progenitor cell is differentiated into a cell lineage of a germ layer selected from the group consisting of ectoderm, mesoderm and endoderm, and/or a specific cell type selected from the group consisting of: a neural, glial, chondroblast, osteoblast, adipocyte, hepatocyte, a smooth muscle cell, a skeletal muscle cell, cardiac cell, pancreatic cell, pulmonary cell, and endothelial cell.

16 . The method of claim 15 , wherein the stem or progenitor cell is differentiated into a chondroblast.

17 . The method of claim 16 , wherein the stem or progenitor cell are cultured under conditions for forming a chondroblast comprising culturing with at least one growth factor selected from the group consisting of: EGF, PDGF, TGF-β1, BMP-2, BMP-12, BMP-13, and BMP-4.

18 . The method of claim 16 , further comprising a step of confirming chondroblast differentiation.

19 . The method of claim 18 , wherein the step of confirming chondroblast differentiation quantitative reverse-transcription-polymerase chain reaction (Q-RT-PCR) for collagen type II and aggrecan transcripts and/or staining with Alcian Blue to demonstrate cartilage matrix production.

20 . The method of claim 1 , wherein the stem or progenitor cell expresses at least one of Oct-4, Nanog, Sox-2, KLF4, c-Myc, Rex-1, GDF-3, LIF receptor, and Stella.

21 . The method of claim 13 , wherein the stem or progenitor cell expresses at least one of Oct-4, Nanog, Sox-2, KLF4, c-Myc, Rex-1, GDF-3, LIF receptor, and Stella.

Assignees

• Brigham & Womens Hospital Inc

Inventors

• Crawford Keith D
• Southgate Christopher

Classifications

• A61P37/02

  Immunomodulators · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• C12N2501/40

  Regulators of development · CPC title

• C12N2501/105

  Insulin-like growth factors [IGF] · CPC title