Methods and compositions for expanding long-term hematopoietic stem cell populations

Patent metadata

Field	Value
Publication number	US-10137154-B2
Application number	US-201414903548-A
Country	US
Kind code	B2
Filing date	Jul 14, 2014
Priority date	Jul 12, 2013
Publication date	Nov 27, 2018
Grant date	Nov 27, 2018

Abstract

The invention generally features compositions and methods for expanding long term hematopoietic stem cells (HSCs) in a population of cells. In particular, the invention relates to a method of expanding long term HSCs by culturing an initial population of HSCs with macrophages that promote self-renewal of long term HSCs. The expanded cell population provides a source of cells for therapeutic treatments utilizing HSC transplantation.

First claim

What is claimed is:

1. A method of expanding an isolated population of hematopoietic stem cells (HSCs) comprising:
a) culturing a starter cell population of HSCs;
b) adding M2 polarized macrophages and optionally at least one macrophage-derived secretion factor to the starter cell population to form an expanding HSC population; and,
c) culturing the expanding HSC population to form an expanded HSC population, wherein the number of long term expanded HSCs is increased in comparison to the number of long term HSCs in the starter cell population, wherein the HSCs have improved expansion and engraftment capabilities compared to HSCs expanded with non-polarized macrophages.

2. The method of claim 1 , further comprising adding additional factors to the starter cell population.

3. The method of claim 2 , wherein the additional factors are selected from the group consisting of cytokines, growth factors, proteins, polypeptides, small molecules, nutrients, expression vectors, and combinations thereof.

Assignees

• Univ Arkansas
• Zhou Daohong
• Luo Yi
• Shao Lijian
• Feng Wei
• Chang Jianhui
• Bioventures Llc

Inventors

• Zhou Daohong
• Luo Yi
• Shao Lijian
• Feng Wei
• Chang Jianhui

Classifications

• A61K35/15

  Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells (presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00) · CPC title

• A61K35/28 Primary

  Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells · CPC title

• C12N5/0647

  Haematopoietic stem cells; Uncommitted or multipotent progenitors · CPC title

• C12N2501/2304

  Interleukin-4 (IL-4) · CPC title

• A61K2035/124

  the cells being hematopoietic, bone marrow derived or blood cells · CPC title