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Understanding Cell Cross-Talk to Prevent Neurodegeneration

Understanding cross-talk between cells in the central nervous system as a way to recode cells to prevent myelin loss

New York Stem Cell Foundation Research Institute
New York City, NY Dr. Valentina Fossati

NSCF partners with the New York Stem Cell Foundation Research Institute to fund research being conducted by Dr. Valentina Fossati, a NYSCF Research Institute Senior Investigator, and her team. The researchers are studying how astrocytes, the “power convertors” of cells in the central nervous system (CNS), can be manipulated to halt or prevent neurodegeneration.

Understanding cross-talk between cells in the central nervous system is the next frontier for the development of new therapies to treat Multiple Sclerosis (MS), Parkinson’s disease, ALS (Lou Gehrig’s disease) and other disorders.

NYSCF’s MS research focuses on the role astrocytes play in the loss or destruction of myelin, the insulation around nerve fibers that allows messages to be transmitted from the brain to other parts of the body. Reprogramming cells to halt myelin loss would prevent the loss of function caused by myelin damage in multiple sclerosis.

NYSCF’s development of novel protocols for re-engineering a patient’s own cells to generate functional astrocytes and oligodendrocytes (myelin-producing cells) significantly advances an understanding of how cells communicate in the CNS. The ability to create a healthy, ongoing source of the patient’s own myelin-producing cells would represent an important step forward in the development of cell-based therapies to halt and reverse MS damage. This grant will advance prior work in this area conducted by NYSCF.

Biography:

Dr. Fossati received her PhD at the University of Bologna – Italy, and joined Dr. Hans Snoeck’s lab at Mount Sinai School of Medicine in 2006, while still a PhD student.

She has been working on the development of the immune system, focusing on B lymphocytes first and, as a post doctoral fellow, on the generation of thymic epithelial cells from embryonic stem cells.

Her interest in the stem cell field goes back to her undergraduate studies, at a time when the concept of regenerative medicine was just emerging as a truly exciting approach to cure diseases. A diagnosis of Multiple Sclerosis (MS) in 2009 shifted her research interest to better understanding the disease and in particular its neurodegenerative component, which is responsible for irreversible neurological disabilities and therefore represents a new target for therapeutic intervention.

Bringing the stem cells expertise to the MS field, she developed a research plan that focuses on modeling MS with human cells, understanding genetic susceptibility by studying patient-specific cells and, ultimately, drug discovery and cell replacement therapies targeting neurodegeneration and de-myelination.

Publications

NATURE METHODS | VOL 15 | SEPTEMBER 2018
Induction of myelinating oligodendrocytes in human cortical spheroids

Cerebral organoids provide an accessible system for investigations of cellular composition, interactions, and organization but have lacked oligodendrocytes, the myelinating glia of the central nervous system. Here we reproducibly generated oligoden-drocytes and myelin in ‘oligocortical spheroids’ derived from human pluripotent stem cells. Molecular features consistent with those of maturing oligodendrocytes and early myelin appeared by week 20 in culture, with further maturation and myelin com-paction evident by week 30. Promyelinating drugs enhanced the rate and extent of oligodendrocyte generation and myelina-tion, and spheroids generated from human subjects with a genetic myelin disorder recapitulated human disease phenotypes. Oligocortical spheroids provide a versatile platform for studies of myelination of the developing central nervous system and offer new opportunities for disease modeling and therapeutic development.

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