Gene specifically expressed in postmitotic dopaminergic neuron precursor cells

Abstract

A novel gene 65B13 expressed specifically and transiently in dopaminergic neuron precursor cells immediately after cell cycle exit was obtained by the present invention. The cellular expression of 65B13 can be used as an index to select cells that are suitable in terms of their safety, survival rate, and network formation ability, for transplant therapy of neurodegenerative diseases such as Parkinson's disease.

Description

CROSS-REFERENCES TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. patent application Ser. No. 10 / 532,264, 371 (c) date of Dec. 28, 2005, which is a U.S. National Phase of PCT / JP03 / 13420, filed Oct. 21, 2003, which claims priority to Japanese Application No. 2002-307573, filed Oct. 22, 2002. All of the aforementioned applications are hereby incorporated by reference in their entireties and for all purposes.STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] NOT APPLICABLE REFERENCE TO A “SEQUENCE LISTING,” A TABLE, OR A COMPUTER PROGRAM LISTING APPENDIX SUBMITTED ON A COMPACT DISK [0003] NOT APPLICABLE BACKGROUND OF THE INVENTION [0004] 1. Technical Field [0005] The present invention relates to the novel 65B13 gene expressed in postmitotic dopaminergic neurons. Dopaminergic neuron precursor cells used in transplant therapy for neurodegenerative diseases such as Parkinson's disease (PD) can be efficiently isolated...

AI Technical Summary

Benefits of technology

[0014] The in situ hybridization results were further supported by immunostaining using an anti-65B 13 antibody (FIG. 13). Moreover, populations of cells expressing 65B13 could be efficiently separated by flow cytometry using an anti-65B13 antibody (FIG. 14).

[0015] According to the above results, anti-65B13 antibodies can be used to obtain pure early-stage dopaminergic neuron precursor cells, by isolating 65B13-expressing cells from ventral midbrain region or cell cultures that contain in vitro-differentiated dopaminergic neurons. Cells obtained in this manner contain only postmitotic precursor cells, and since only the cell type of interest is isolated, these cells are extremely safe even when used for transplant therapy. Since the earliest possible precursor cells are used, high therapeutic efficacy can be expected in terms of their survival rate, network formation ability, and such. Further, in the cases where the best therapeutic effects cannot be achieved by these early precursor cells obtained immediately after cell cycle exit, and where the use of matured cells is required, early precursor cells obtained by this method can simply be cultured in vitro to mature into a suitable stage of differentiation. Thus, materials that are in a differentiation stage suitable for the target transplant therapy can be easily prepared (FIG. 12).

Problems solved by technology

One of the major problems in Parkinson's disease (PD) transplant therapy at the moment is that in vitro differentiated dopaminergic neuron precursor cells and midbrain ventral zone of aborted fetuses are both mixtures of myriad types of cells.

Further, in the cases where the best therapeutic effects cannot be achieved by these early precursor cells obtained immediately after cell cycle exit, and where the use of matured cells is required, early precursor cells obtained by this method can simply be cultured in vitro to mature into a suitable stage of differentiation.

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