Grants Funded
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Research Abstracts
Search The PSF database to have easy access to full-text grant abstracts from past PSF-funded research projects 2003 to present. All abstracts are the work of the Principal Investigators and were retrieved from their PSF grant applications. Several different filters may be applied to locate abstracts specific to a particular focus area or PSF funding mechanism.
Neural Stem Cells Improve Muscle Preservation Following Devervation
Principal Investigator
Tateki Kubo
Tateki Kubo
Year
2006
2006
Institution
Massachusetts General Hospital
Massachusetts General Hospital
Funding Mechanism
Basic Research Grant
Basic Research Grant
Focus Area
Peripheral Nerve
Peripheral Nerve
Abstract
Brachial plexus palsies, whether obstetrical or traumatic, are devastating injuries with significant impairment of the affected limb, resulting in functional paralysis, sensory deficits, as well as deep psychological scars. Because of the prolonged delay in nerve regeneration, chronic muscle atrophy and fibrosis continues to be a severe, irreversible impediment to recovery. Current microsurgical techniques have reached their limit in terms of improving the results of brachial plexus reconstruction, we hypothesize that stem cell transplantation may be able to further enhance outcomes by better supporting the biological integrity of the injured muscle and nerve. The requirements for optimal functional recovery after a brachial plexus injury are that (1) the regenerating axons make functional connections with their original muscle cells and (2) the number and size of the motor units in those muscles are restored. To prevent prolonged denervation atrophy and eventual fibrosis, we have previously transplanted embryonic stem (ES) cell derived motor neurons (MNs) into denervated muscles (Craff, et. at., PRS in press). These MNs can provide trophic support to the muscle by forming neo-neuromuscular junctions and upregulating specific growth factors, preserving motor unit integrity for a period of one week. In the current study, we propose to (1) examine the effect of this transplant on the functional outcome after nerve repair and (2) characterize the interaction on a molecular level. To better understand the interaction of the stem cell derived MNs and muscle cells, an in vitro co-culture model of stem cell derived MNs and myotubes will be used to perform a microarray analysis. If this interaction can be better understood, perhaps a method of preserving motor unit health in the denervated state could be achieved, ultimately improving outcomes in brachial plexus reconstruction.
Brachial plexus palsies, whether obstetrical or traumatic, are devastating injuries with significant impairment of the affected limb, resulting in functional paralysis, sensory deficits, as well as deep psychological scars. Because of the prolonged delay in nerve regeneration, chronic muscle atrophy and fibrosis continues to be a severe, irreversible impediment to recovery. Current microsurgical techniques have reached their limit in terms of improving the results of brachial plexus reconstruction, we hypothesize that stem cell transplantation may be able to further enhance outcomes by better supporting the biological integrity of the injured muscle and nerve. The requirements for optimal functional recovery after a brachial plexus injury are that (1) the regenerating axons make functional connections with their original muscle cells and (2) the number and size of the motor units in those muscles are restored. To prevent prolonged denervation atrophy and eventual fibrosis, we have previously transplanted embryonic stem (ES) cell derived motor neurons (MNs) into denervated muscles (Craff, et. at., PRS in press). These MNs can provide trophic support to the muscle by forming neo-neuromuscular junctions and upregulating specific growth factors, preserving motor unit integrity for a period of one week. In the current study, we propose to (1) examine the effect of this transplant on the functional outcome after nerve repair and (2) characterize the interaction on a molecular level. To better understand the interaction of the stem cell derived MNs and muscle cells, an in vitro co-culture model of stem cell derived MNs and myotubes will be used to perform a microarray analysis. If this interaction can be better understood, perhaps a method of preserving motor unit health in the denervated state could be achieved, ultimately improving outcomes in brachial plexus reconstruction.