Use of marrow-derived glial progenitor cells as gene delivery vehicles into the central nervous system

Abstract

The present disclosure relates to a method for introducing a hematopoietic cell into the brain of a mammal, by administering bone marrow-derived progenitor cells into the body of the mammal by intravenous injection. The bone marrow-derived cell is preferably a cell that differentiates into a glial cell. The disclosure also relates to a method for delivery of therapeutic protein molecules into the brain of a mammal, by administering to a mammal an effective amount of bone marrow-derived progenitor cells which contain a gene having a nucleic acid sequence that encodes a functional therapeutic protein. Isolated recombinant cells and a pharmaceutical composition are also provided.

Description

REFERENCE TO RELATED APPLICATIONS [0001] This is a divisional of U.S. patent application Ser. No. 10 / 122,703, filed Apr. 11, 2002, now allowed, which is a continuation-in-part of U.S. patent application Ser. No. 09 / 819,096, filed Feb. 16, 2001, now abandoned, which is a continuation of U.S. patent application Ser. No. 09 / 058,160, filed Apr. 10, 1998, now abandoned, which claims the benefit of U.S. Provisional Application No. 60 / 036,592, filed Apr. 10, 1997.FIELD [0002] The present disclosure relates to methods for introducing hematopoietic cells into the brain of a mammal, the differentiation of adult bone marrow cells into glial cells, and the use of marrow-derived glial progenitor cells as gene delivery vehicles into the brain. BACKGROUND [0003] Glial cells are thought to derive embryologically from either myeloid cells of the hematopoietic system (microglia) or neuroepithelial progenitor cells (astroglia and oligodendrocytes). However, it is unclear whether the glia in adult brai...

AI Technical Summary

Benefits of technology

[0016] Although many neurotrophic factors show promise in the treatment of CNS disorders, their use has been hindered by their inability to cross the blood-brain barrier and by their limited diffusion into CNS tissues (34). In addition, adverse effects have been reported after systemic administration of some neurotrophins (35). Using marrow-derived cells to deliver therapeutic proteins directly to the site of CNS pathology likely would be more benign than systemic administration of toxic molecules. In addition, using vectors with cell type-specific promoters could restrict gene expression specifically to reactive astroglia or microglia, thereby providing greater therapeutic precision for gene therapy of CNS disease.

Problems solved by technology

However, it is unclear whether the glia in adult brains free of disease or injury originate solely from cells present in the brain since the fetal stage of development, or if there is further input into such adult brains from cells originating outside the central nervous system (CNS).

However, the developmental origin of microglia remains debatable (2,3).

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