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  • Updated 10.29.2020
  • Released 12.05.2000
  • Expires For CME 10.29.2023

Cell therapy for neurologic disorders

Introduction

Overview

Cell therapy for neurologic disorders means the use of cells of neural or nonneural origin to replace, repair, or enhance the function of the damaged nervous system. Numerous technologies are involved in the development of cell therapies. These include the use of stem cells and genetic modification of cells. Implantation of genetically modified cells is a form of gene therapy. This article describes the development of cell therapies, both preclinical and clinical, in several disorders. Most of the work has been done in cell therapy of Parkinson disease. Other neurodegenerative disorders, such as stroke, epilepsy, and injuries of the nervous system are also amenable to cell therapy.

Key points

• Several types of cells have been transplanted into the nervous system for the treatment of neurologic disorders.

• Cells have been genetically modified to secrete therapeutic substances in vivo.

• The current focus of investigations is on stem cells, which may replace, repair, or enhance the function of damaged cells of the nervous system.

Historical note and terminology

Cell therapy for neurologic disorders means the use of cells of neural or nonneural origin to replace, repair or enhance the function of the damaged nervous system. This is also called neurotransplantation, and is usually achieved by transplantation of the cells that are isolated and may be modified, for example, by genetic engineering. Tissue engineering in the nervous system is the science of designing, creating, and realizing systems where neural cells are organized in a controlled manner, to perform appropriate diagnostic, palliative, and therapeutic tasks in the nervous system. The focus of this article is on cells used as therapeutic agents. Genetically modified cells that secrete therapeutic substances such as neurotrophic factors, or the use of cells as vectors for gene therapy and vehicles for drug delivery to the central nervous system are described in other clinical summaries. An overlap between cell therapy, gene therapy, tissue engineering, and regenerative medicine applies to the nervous system as well (29).

The historical landmarks in the evolution of cell therapy for neurologic disorders are shown in Table 1. Over the last decade, neural transplantation has progressed from being an experimental technique for studying regeneration and plasticity in the brain to clinical trials in human neurologic diseases.

Table 1. Historical Evolution of Cell Therapy and Neural Grafting for Neurologic Disorders

Year

Landmark

1890

First attempt at neural grafting at New York University--cerebral cortex derived from adult cats into adult dogs--was unsuccessful (58).

1905

Experiments conducted by Saltykow at the University of Basel showed survival of neurons for several days following autograft of cerebral cortex in young rabbits (Bjorklund and Stenevi 1985).

1917

Survival of the embryonic brain allografts in rats (17).

1940

Survival of the fetal mammalian CNS tissue transplanted to the brain (36).

1962

First use of the term “blood stem cell” in peripheral blood (23).

1970-79

Numerous methodological advances. Demonstration of the reestablishment of neural circuits by neural grafts.

1979

Demonstration that brain graft could influence host-brain function in an animal model of neurodegenerative disorder (06).

1981

Embryonic stem cells first isolated from the inner cell mass of developing mouse blastocysts (18).

1987

Clinical trials of human fetal dopaminergic brain tissue transplants in Parkinson disease patients started in Sweden (37).

1988

Transplantation of fetal substantia nigra and adrenal medulla to the caudate nucleus in patients with Parkinson disease in Mexico (40).

1990

Fetal striatal graft in a primate model of Huntington disease was shown to survive and provide partial functional restitution (24).

1990

Myelin formation reported following transplantation of normal fetal glia into myelin-deficient rat spinal cord (51).

1991

Improvement reported in a patient with Huntington disease following fetal neural transplantation (39).

1994

Development of an immortalized stem cell line for neurotransplantation (33).

1998

First intracerebral cell transplant to reverse brain damage caused by stroke.

1998

First description of embryonic stem cell lines derived from human blastocysts (59).

2000

Human brain stem cells isolated directly from brain tissue.

2000

Implantation of cultured neuronal cells into the brains of stroke patients.

2007

Induction of pluripotent stem cell lines derived from human somatic cells, which will facilitate development of autologous adult stem cell therapy.

1st decade of 21st century

Clinical trials of adult stem cells in neurologic disorders administered intravenously as well as implanted directly in the brain.

2010

First use of chimeric antigen receptor (CAR)-T cells that recognized the B cell antigen CD19 to treat a patient with lymphoma that underwent a dramatic regression.

2011

Nobel Prize in Physiology or Medicine awarded to Dr. Ralph Steinman for his discovery of the dendritic cell and its role in adaptive immunity.

2012

Nobel Prize in Medicine awarded to John Gurdon of Cambridge University in the UK and Shinya Yamanaka from Kyoto University of Japan for discovery of induced pluripotent stem cells.

2013

Cerebral organoids model human brain development and microcephaly (35).

2014

Generation of pluripotent human embryonic stem cells from dermal fibroblasts by somatic cell nuclear transfer (13).

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