Tolerizing allografts of pluripotent stem cells

• US 20060002906A1
• Filed: 09/02/2005
• Published: 01/05/2006
• Est. Priority Date: 11/22/2000
• Status: Abandoned Application

• Current Assignee: Asterias Biotherapeutics Incorporated (Lineage Cell Therapeutics, Inc.)
• Original Assignee: Asterias Biotherapeutics Incorporated (Lineage Cell Therapeutics, Inc.)
• Inventors: Kay, Robert M., Chiu, Choy-Pik
• Application Number:
  US11/219,477
• Publication Number:
  US 20060002906A1
• Time in Patent Office: Days
• US Class Current: 424/93.210
• CPC Class Codes: A61K 2035/122 for inducing tolerance or supression of immune responses
• 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: 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: C12N 2506/02 from embryonic cells

Abstract

This disclosure provides a system for overcoming HLA mismatch between an allograft derived from stem cells, and a patient being treated for tissue regeneration. A state of specific immune tolerance is induced in the patient, by administering a population of tolerizing cells derived from the stem cells. This allows the patient to accept an allograft of differentiated cells derived from the same source. This invention is important because it allows a single line of stem cells to act as a universal donor source for tissue regeneration in any patient, regardless of tissue type.

Claims

1. A method for preparing cells for therapeutic use, comprising:

a) differentiating human pluripotent stem (hPS) cells into a first cell population; and

b) differentiating human pluripotent stem (hPS) cells into a second cell population;

wherein the first cell population is MHC compatible with the second cell population, and whereupon administration of the first population to an individual renders the individual immunotolerant to the second cell population.

2. The method of claim 1, wherein the first cell population and the second cell population are differentiated from the same hPS cells or their progeny.

3. The method of claim 1, wherein the first cell population predominantly comprises mesoderm cells.

4. The method of claim 1, wherein the first cell population has characteristics of hematopoietic progenitor cells, blood leukocytes, leukocyte precursor cells, macrophage-like cells, dendritic cells, or mesenchymal stem cells.

5. The method of claim 1, wherein the first cell population expresses one or more of the following markers:

CD34, T-cell receptor, HLA Class II, CMRF-44, CMRF-56, DEC-205, S100, or CTLA-4.

7. The method of claim 1, wherein the second cell population comprises one of the following cell types or their lineage-restricted precursors:

hepatocytes, neurons, oligodendrocytes, astrocytes, cardiomyocytes, or osteogenic cells.

6. A method for preparing a first cell population that renders an individual to whom it is administered immunotolerant to a second cell population, comprising differentiating human pluripotent stem (hPS) cells into a mixed cell population, and enriching from the mixed population cells that express CD34, T-cell receptor, HLA Class II, CMRF-44, CMRF-56, DEC-205, S100, or CTLA-4.

8. A combination of pharmaceutical compounds, comprising in separate containers:

a) a first cell population that has been differentiated from human pluripotent stem (hPS) cells into a phenotype that renders a subject to whom it is administered immunotolerant to a second cell population; and

b) the second cell population that is MHC compatible with the first cell population.

9. The pharmaceutical compounds of claim 8, wherein the first cell population and the second cell population are differentiated from the same hPS cell line.

10. The pharmaceutical compounds of claim 8, wherein the first cell population predominantly comprises mesoderm cells.

11. The pharmaceutical compounds of claim 8, wherein the first cell population has characteristics of hematopoietic progenitor cells, blood leukocytes, leukocyte precursor cells, macrophage-like cells, dendritic cells, or mesenchymal stem cells.

12. The pharmaceutical compounds of claim 8, wherein the first cell population expresses one or more of the following markers:

CD34, T-cell receptor, HLA Class II, CMRF-44, CMRF-56, DEC-205, S100, or CTLA-4.

13. The pharmaceutical compounds of claim 8, wherein the second cell population comprises one of the following cell types or their lineage-restricted precursors:

hepatocytes, neurons, oligodendrocytes, astrocytes, cardiomyocytes, or osteogenic cells.

14. A method for reconstituting cellular function in an individual, comprising administering to the individual a first cell population and a second cell population, both differentiated from human pluripotent stem (hPS) cells, wherein the first cell population is MHC compatible with the second cell population,

whereupon administration of the first cell population renders the individual immunotolerant to the second cell population;

and

whereupon administration of the second cell population reconstitutes the cellular function.

15. The method of claim 14, wherein the phenotype of the first cell population expresses one or more of the following markers:

CD34, T-cell receptor, HLA Class II, CMRF-44, CMRF-56, DEC-205, S100, or CTLA-4.

16. The method of claim 14, wherein the first cell population is administered to the circulation.

17. The method of claim 14, wherein the cellular function that is reconstituted in the individual is the function of hepatocytes, neurons, oligodendrocytes, astrocytes, cardiomyocytes, or osteogenic cells.

18. The method of claim 14, wherein administration of the second cell population occurs at least 2 weeks after administration of the first cell population.

19. The method of claim 14, wherein the first cell population and the second cell population are differentiated from the same hPS cells or their progeny.

20. A method of preparing an individual for therapy to reconstitute their cellular function, comprising administering to the individual a first cell population differentiated from human pluripotent stem (hPS) cells, thereby rendering the individual immunotolerant to a second cell population also differentiated from hPS cells that is MHC compatible with the first cell population, wherein the therapy comprises administering to the individual the second cell population, thereby reconstituting the cellular function in the individual.