Dedifferentiation and stem cell research :

Description of projects available to graduate students:
The use of stem cells in cell-replacement therapy continues to pose numerous problems due to inefficient methods for stem cell propagation and differentiation, and host rejection of allogeneic cells. The increasingly evident link between stem cells and cancer has also complicated the value of using stem cells in cell-replacement therapy. Cellular dedifferentiation is the natural healing process by which some vertebrates (e.g., newt, salamander) are able to regenerate a missing tail, leg, or even an eye at any time throughout their lives. The ability to promote dedifferentiation and obtain a population of multipotent progenitor cells may help to overcome the existing limitations of stem cell therapy. Under our current proposal, the goal is to identify a potential stimulator of dedifferentiation within human skeletal muscle, a tissue with a proven aptitude for self-regeneration. Dr. Li’s laboratory intends to seek this potential stimulator of dedifferentiation in skeletal muscle cells both in vitro and in vivo. In fact, this lab’s collected data indicates that certain growth factors may be viable candidates because they have demonstrated the ability to stimulate dedifferentiation in injured skeletal muscle. A major component of this project is to increase the number of available stem cell-like cells versus muscle specific induced pluripotent stem (iPS) cells from skeletal muscle under the assumption that dedifferentiation could substantially increase that number. The human body contains a large amount of easily accessible skeletal muscles that are likely sources of numerous populations of adult stem cells. The muscle derived stem cell has been observed differentiating into different cell lineages which include: myogenic, osteogenic, neurogenic, and other lineages. Our recent research showed that ciliary neurotrophic factor (CNTF) can similarly induce myoblasts to adopt a multipotent phenotype capable of redifferentiating into adipocytes, glial, and neuronal cells. This is significant from a therapeutic standpoint, as they have the unrivaled capacity to differentiate into different phenotypic lineages and regenerate various tissues, including skeletal muscle, spine, nerve, bone, and cartilage.

Another interesting project that is developing in Dr. Li’s laboratory involves iPS cells from human skin tissues. The proposal intends to use a cocktail of growth factors or gene transfer to induce human skin derived stem cells or fibroblasts into pluripotent stem cell-like cells. In our previous study, the skin derived stem cells have been applied to repair spinal cord injury in the mouse model. We are now investigating if human skin iPS cells could be beneficial on accelerating the spinal cord repair with iPS cell treatment.

The overall goal of this project is to increase the number of stem cell-like cells made available from the skin and skeletal muscle pool. The human body contains a large amount of easily accessible skin and skeletal muscle that is the likely source of numerous populations of adult stem cells that have an inherent capacity to differentiate into different phenotypic lineages and regenerate various tissues, including skeletal muscle, the spinal cord, various nerve cells, and cartilage. To be able to more fully comprehend and control this process and the intricacies of signaling involved would be of exceptionally important clinical value.

Techniques graduate student will learn:
Cell culture, Molecular techniques, immune staining