3D_SpineTracker - Automated remyelination detection and classification of axons for sub-acutely injured spinal cord section images for temporal tracking of remyelination after stem cell treatment
3D_SpineTracker Spinal cord injury, or myelopathy, is a disturbance of the spinal cord that results in loss of sensation and mobility. It can be caused by trauma or disease, and it can be either complete or incomplete. Symptoms include loss of sensor or motor function, loss of reflexes, and loss of bladder or bowel control. A traumatic injury site is typically characterized by a loss of the myelin layer, which serves as an insulator for the axon and as a track along which regrowth can occur. Unmyelinated axon fibers do not regenerate. Preliminary studies in rats and mice have shown that human embryonic stem cells have the capability to differentiate into various cell types, aiding in the remyelination of axons. Animals undergoing this treatment have been shown to exhibit myelin sheaths restoration, which ultimately lead to regaining mobility. In order to quantify and control this process, it is crucial to develop methods for precise temporal tracking of remyelinated axons at the injury site. This can be done by distinguishing between two cell types, namely oligodendrocytes and Schwann cells, and by accurately computing the cell count for each type. In order to monitor cell development at the repair site, histological sections are taken at increasing time intervals, and the cell count is determined for each time step. The results of this quantitative analysis can be visualized in an animated, 3D rendering of the spinal cord injury site. One of the challenges for a statistical analysis is the large amount of histological sections and the large number of cells in each section. The development of a growth model as a quantitative analysis tool is a critical step toward a timely deployment of the treatment method in a human clinical trial.
Statement of Benefit to California:
A stem cell is a type of cell found in both animals and humans that has the potential to develop into many different types of specialized cells in the body. Scientists found that stem cells have the potential to migrate toward injury sites and perform repair functions by replacing damaged cells with healthy cells. The SEED Grant will allow scientists to conduct research toward a better understanding of how stem cells differentiate into certain cell types, thus offering new treatment options ranging from tissue replacement to restoration of mobility functions after spinal cord injury. The citizens of the State of California will be among the first to benefit from this kind of research. Clinical trials on animals and humans are currently underway and are expected to lead to better insight into the processes that cause a stem cell to develop into a new cell type. More research is needed to fully understand the mechanisms of stem cell migration and differentiation. Preliminary results from animal studies indicate that new treatment options could be developed for spinal cord injury patients, in particular for those with recent post-traumatic conditions. It may be a long way until full recovery from spinal cord injury is possible, and even partial restoration of some mobility or other body functions, such as bowel or bladder control, would be considered a tremendous success. Computational methods will be developed to aid in this endeavor. The quantitative analysis and 3D visualization software to be developed under this grant will lead to an improved understanding of how stem cell derived progenitor cells migrate into the injury site to perform repair on the myelin sheaths that are critical for restoring function in axons.
SYNOPSIS: This proposal is designed to develop automated detection of the cell type responsible for remyelination in spinal cord injury following transplantation of human embryonic stem cell (hESC) - derived oligodendrocytes. INNOVATION AND SIGNIFICANCE: This proposal is not very innovative. The concept has significance in stem cell research and it would have benefited the proposal for that significance to have been placed in the context of a robust research plan. STRENGTHS: The idea has novelty and if successful could have practical significance. From the extremely scant information provided, the proposal seems straightforward and the goals may be attainable with the allocated time and resources. WEAKNESSES: There is a lack of detail on how the applicant plans to carry out this proposal. The proposal is very brief with few to no details given - e.g., there is no note in Figure 1 about what the images represent and 1a is certainly not typical of a normal spinal cord. This should have been detailed more. The proposal does not detail why the geometric processing and rendering cannot be achieved with existing software and therefore constitutes the basis of a developmental project. Details on distinguishing Schwann cells from oligodendrocytes are scant. The proposal would have benefited from the inclusion of references. The proposal is furthermore very specialized and of interest to only a few investigators. DISCUSSION: There was no further discussion following the reviewers' comments.