Methods of improving stem cell homing and engraftment

• US 8,846,393 B2
• Filed: 11/29/2006
• Issued: 09/30/2014
• Est. Priority Date: 11/29/2005
• Status: Active Grant

• Current Assignee: Gamida Cell, Ltd.
• Original Assignee: Gamida Cell, Ltd.
• Inventors: Peled, Tony
• Primary Examiner(s): LEAVITT, MARIA GOMEZ
• Application Number:
  US12/085,406
• Publication Number:
  US 20100061963A1
• Time in Patent Office: 2,862 Days
• Field of Search: 435/377, 435/325, 435/372
• US Class Current: 435/377
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C12N 2500/38 Vitamins
• CPC Class Codes: C12N 2501/00 Active agents used in cell culture processes, e.g. differentation
• CPC Class Codes: C12N 2501/50 Cell markers; Cell surface determinants
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors

Abstract

A method of enhancing cell engraftment potential is provided. The method comprising ex-vivo or in-vitro subjecting a population of cells to an amount of nicotinamide for a period of time sufficient to effect the population of cells, thereby enhancing cell engraftment potential.

Claims

1. A method of enhancing cell homing and engraftment potential, the method comprising ex-vivo or in vitro culturing a population of isolated CD34+ hematopoietic stem cells in the presence of 1 to 10 mM nicotinamide for a period of time of 5-30 hours, wherein said period of time is insufficient for proliferation of said isolated CD34+ hematopoietic stem cells, and wherein said culturing results in down-regulation of CD26 expression as compared to isolated CD34+ hematopoietic stem cells cultured in the absence of nicotinamide.

2. The method of claim 1, wherein said nicotinamide is selected from the group consisting of nicotinamide, a nicotinamide analog, a nicotinamide metabolite, a nicotinamide analog metabolite and derivatives thereof.

3. The method of claim 1, wherein said population of CD34+ hematopoietic stem cells is from a source selected from the group consisting of umbilical cord blood cells, mobilized peripheral blood cells, and bone marrow cells.

4. The method of claim 1, wherein said population of CD34+ hematopoietic stem cells is from bone marrow or peripheral blood.

5. The method of claim 1, wherein said population of CD34+ hematopoietic stem cells is from neonatal umbilical cord blood.

6. The method of claim 1, wherein said population of CD34+ hematopoietic stem cells is from a mononuclear cell fraction.

7. The method of claim 1, further comprising the step of selecting a population of cells enriched for hematopoietic stem cells via CD34 prior to, concomitant with or following said step of ex-vivo culturing.

8. The method of claim 7, wherein said selecting is effected via CD133.

9. The method of claim 7, wherein said selecting is effected via CD34/CD38.

10. The method of claim 1, wherein said population of cells is cultured in 5 mM nicotinamide for 20 hours.