Multimodal Precursor-derived AstroCyte Therapy (MPACT)
Injuries to the brain, whether caused by trauma or degenerative disease, are highly debilitating and currently without effective treatment. The common denominator to both traumatic and neurodegenerative disease in CNS is the disruption of the environment at the injury site. This disruption prevents the repair of damaged neurons and perpetuates the disease process.
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Precursor Cells and Disease
The complexity and plasticity of the mammalian nervous system have been major obstacles in identifying the cell biological processes that result in the manifestation of a disease. This is particularly true for genetic diseases, in which the causative mutations may have been identified, but the consequences at the cellular or tissue level remain unclear, thereby dramatically limiting our ability to devise effective therapies.
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Lineage Restriction and Astrocyte Identity
Although the exact mechanisms of progressive lineage restriction of stem cells and progenitor cells in the CNS remain largely unknown, it is clear that lineage-restricted progenitor cells are the real work-horses of organogenesis and tissue building. Stem cells in contrast, function as a source of the lineage-restricted progenitor cells and only in the earliest stages of development do they constitute a numerically significant population in any tissue. Consequently understanding the signals that control the proliferation and lineage decisions of restricted progenitors, will be essential to understanding tissue formation and repair.
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Inducible Pluripotent Stem Cells
The availability of human embryonic stem cells (hESC) and inducible, pluripotent stem cell (iPSC)-technology through the University of Rochester Stem Cell and Regenerative Medicine Institute, and the Upstate cGMP Facility, provide unique opportunities to establish new in vitro models of CNS disease, and to develop new cell therapies.
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