Fetal Research and Applications A Conference Summary (1994) / Chapter Skim
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Session IV: Fetal Tissue Transplantation
Session IV: Fetal Tissue Transplantation
Pages 44-59
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From page 44... ...
Progenitor cells give birth to daughter cells through the process of mitosis, in which they double their chromosomal package and then split in half. In the forming of the cerebral cortex, the first cells to be born and migrate out from the ventricular surface are destined for the deepest layers of the cortex, layers five and six.
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From page 45... ...
In animal experiments designed to determine the developmental potential of cortical neurons, cell groups containing progenitor cells were removed from developing rat brains at specific stages and transplanted into brains at different stages of development. For example, cells normally destined to become layersix neurons were transplanted, before migration, into an environment in which the deep layers had already been generated and upper-layer neurons were in the process of migrating.
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From page 46... ...
One proposed mechanism for asymmetric division was that the mother cell splits in a plane parallel to the ventricular surface, thus leaving one cell still adherent, or moored, to the ventricular surface while the other cell migrates away. Another idea was that there might be observable structural, or morphological, differences between two daughter cells that behaved differently.
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From page 47... ...
One path toward developing a strategy for understanding neuronal complexity is to focus initial attention on stem cells, the multipotential cells from which neurons form during fetal development. Neuroepithelial stem cells, which line the walls of the embryonic neural tube (the neuroepithelium)
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From page 48... ...
These findings in animals demonstrate that embryonic neural precursor cells can be preserved in culture for long periods of time yet still be capable of differentiating when placed into a recipient brain. Transplantation of embryonic cells into adult brains raises the possibility of providing a useful therapy for neurodegenerative diseases, many of which are intractable and impose terrible personal, social, and economic costs.
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From page 49... ...
It is an area, nevertheless, that is under active investigation. Fetal Tissue Transplantation for Patients with Parkinson's Disease RICHARD ROBBINS Yale University School of Medicine, New Haven, Connecticut Upwards of a million people in the United States have Parkinson's disease, a progressively degenerative condition affecting movement.
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From page 50... ...
The events in cell differentiation are being studied in cultured substantia nigra neurons and glial cells for insights into why cells die in Parkinson's patients. The effects of growth factors are being examined to see if they can be used to increase survival of dopamine cells in culture.
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From page 51... ...
The lifting of the ban on fetal tissue research will hopefully enable research on this disease to go forward more quickly. Improving Fetal Neuronal Graft Technology Through the Use of Nonhuman Primates to Meet the Needs of Human Therapeutic Applications for Parkinson's Disease JOHN R
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From page 52... ...
Translating that information from the monkey to the human gestational period has not yet been done, in large part because of the prohibition on fetal tissue research. Dopamine neurons, arising in the substantia nigra region of the midbrain, normally send out their axons across the brain to target cells in the striatum.
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From page 53... ...
This represents about one-third the normal adult complement of dopamine neurons derived from the mesencephalon, a critical brain region in Parkinson's disease. These neurons also were characterized by the presence of extensive outgrowth of axons and dendrites into the host brain, which suggests the opportunity for functional integration between grafted and host tissue.
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From page 54... ...
Recognition is achieved by a virtually unlimited repertoire of receptor molecules on white blood cells, or lymphocytes. Lymphocytes express specific receptors in response to specific molecules on invaders (antigens)
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From page 55... ...
Isolation of Candidate Human Stem Cells Using SCID-hu Mice Implanted with Human Fetal Tissue IRVING WEISSMANl Stanford University School of Medicine, Stanford, California Hematopoiesis is the process through which all the different types of blood cells are formed, from red blood cells, to T and B lymphocytes, to a number of different types of so-called white blood cells. Given the multitude of human 1Dr.
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From page 56... ...
A search of several years' duration was conducted to isolate true stem cellscells not yet committed to a particular destiny—in the bone marrow cell populations of experimental mice. Sorting methods involved the use of monoclonal antibodies that, when fully catalogued and mapped, can home in on specific types of cells in a mix by recognition of distinct cell-surface antigens (markers)
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From page 57... ...
Human fetal thymic grafts implanted in SCID mice produce human T cells tolerant of both the mouse and their own human tissue, but fully reactive to other tissue. These grafts, as well as transplanted human fetal bone marrow, will reconstitute all the human blood cell types.
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From page 58... ...
, but the clotting factors produced by the baboon liver differed significantly and resulted in severe clotting abnormalities in the recipient. The primary barrier to the clinical reality of xenografts is that the recipient mounts a much more pronounced rejection response to nonhuman donor tissues.
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From page 59... ...
These separated antibody fragments were shown in tissue culture experiments, and eventually in transplantation experiments, to mask the antigenic sites of the donor tissue and protect it from the host's immune system. In the initial experiments, monoclonal antibodies were used to engage the donor cell binding sites, thereby making them unavailable for binding by T cells.
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