Satellite cell activity and self-renewal in patients with cerebral palsy
| Author(s) | Yeager, Stephanie Kim | |
| Date Accessioned | 2017-12-04T15:41:47Z | |
| Date Available | 2017-12-04T15:41:47Z | |
| Publication Date | 2017 | |
| SWORD Update | 2017-09-05T16:30:09Z | |
| Abstract | Cerebral palsy is a heterogeneous group of movement disorders which may worsen over time despite being caused by a static trauma to the developing brain. Spasticity develops in about 80 % of CP cases and is associated with alterations in muscle structure, overall stiffness within and around muscle fibers, as well as bone deformities. To provide patients with long term relief, surgical approaches to correct alterations in gait or bone structure are typically employed to alter the length or location of spastic muscles. While initially effective, surgical results can be temporary and studies have shown that recurrence to the pre-surgical state develops in about 40% of hip-related surgeries. A possible explanation for the high rate of recurrence is that surgery does not address the underlying pathology associated with spastic muscle. Such pathologies can include increased ECM-related stiffness, contracture of the muscle, and altered sarcomere lengths, all of which may be associated with alterations in CP muscle growth and repair. Recent studies suggest that muscle in patients with CP lacks regenerative capacity, and a potential cause may be alterations in the activity of muscle satellite cells. Additionally, as multiple pathways which alter satellite cell activity have ties to metabolism, reduced ability to maintain the satellite cell pool may be the result of altered nutritional metabolism that is often associated with a diagnosis of CP. The regenerative behavior of muscle satellite cells, which are responsible for reparative myogenesis, is an area of research that has received much attention. It has been recently reported that CP muscle contains about 50% fewer satellite cells compared to control muscle, and researchers have suggested that this reduction in the satellite cell reserve may explain deficient muscle repair and contracture in CP. Currently, the reasons for reduced myosatellite cell numbers in CP is not known. Present studies were undertaken to evaluate if extrinsic differences between CP and control satellite cells are associated with reduced abilities to form muscle or to replenish the satellite cell pool. To determine if CP satellite cells have reduced abilities to form muscle or self-renew, control and CP satellite cell proliferation, self-renewal, and myogenic fusion were compared under basic culture conditions (tissue culture plastic) and on substrates of increasing stiffness. Immunofluorescence assays were performed on satellite-cell derived myoblasts isolated from skeletal muscle biopsies of patients with CP and controls. Cells were grown and differentiated on biomimetic substrates of two different physiological stiffnesses and compared with cells grown on standard tissue culture polystyrene and substrate-coated tissue culture polystyrene. Results indicated that, while control satellite cells proliferated about 20% faster than CP satellite cells (p<0.001 at 24 hours of culture), fusion indices were similar after 7 days of differentiation. Upon examining the effects of substrate stiffness on self-renewal, data showed that control satellite cells maintained a significantly higher proportion of Pax7 expressing cells on softer substrates (3.5 and 12 kPa vs LN coated TCPS, p<0.05) both during the early proliferative phase of growth, (at 24 hours of culture) and at 7 days post induction of differentiation (p<0.001). No stiffness-dependent significant effects were seen in CP satellite cells for proliferation rate, self-renewal, or myogenic fusion index. Further research is needed to elucidate if alterations exist in their machinery responsible for mechano-sensory activation. | en_US |
| Advisor | van Golen, Kenneth L. | |
| Advisor | Akins, Robert E., Jr. | |
| Degree | M.S. | |
| Department | University of Delaware, Department of Biological Sciences | |
| DOI | https://doi.org/10.58088/0q5n-rn05 | |
| Unique Identifier | 1013879637 | |
| URL | http://udspace.udel.edu/handle/19716/21752 | |
| Language | en | |
| Publisher | University of Delaware | en_US |
| URI | https://search.proquest.com/docview/1957958369?accountid=10457 | |
| Keywords | Biological sciences | en_US |
| Keywords | Biomaterials | en_US |
| Keywords | Cerebral palsy | en_US |
| Keywords | Myogenesis | en_US |
| Keywords | Satellite cells | en_US |
| Keywords | Stem cells | en_US |
| Title | Satellite cell activity and self-renewal in patients with cerebral palsy | en_US |
| Type | Thesis | en_US |