Group Project Grants
Nine discrete projects comprise the University’s group project, Directing hES Derived Progenitor Cells into Musculoskeletal Lineages headed by David Rowe and based at the UConn Health Center. Collectively, the participating researchers are studying how embryonic stem cells could help rebuild bone, cartilage, skin and muscle.
Project 1: Directing ES Cells to a common progenitor cell for musculoskeletal
tissue generation. Alexander Lichtler, principal investigator.
The researchers are striving to develop a method that will use well-defined culture conditions to promote differentiation of human embryonic stem cells into a pure population of mesoderm cells, cells from the embryonic layer that ultimately develops into all connective tissue, muscle, bone and the urogenital and circulatory systems. Those cells would then be used by other members of the grant team to differentiate into the type of cells they are studying. Additionally, the Project 1 group will be aiding Dr. Mina (Project 6), producing embryonic stem cells equipped with fluorescent protein markers that come on when the cells have reached a certain differentiation stage.
Project 2: FACS isolation of progenitors and generation novel cell surfaces
antibodies. Leonardo Aguila, principal investigator.
In order for researchers to use stem cells for regenerative therapies, the design of methods for the correct identification of stem cells is crucial. One of the best approaches - not only to characterize different cell types, but also to isolate them - is the generation of antibodies against cell surface molecules. The Project 2 group has developed unique tracking systems for musculoskeletal development to visualize progenitor cells with the ability to develop into cartilage, bone, fat and muscle. These systems employ genetic techniques that add genetic information to embryonic stem cells to make them express fluorescent protein at defined stages of their development.
Project 3: Microarray. Dong Shin, principal investigator.
The project focuses on state of the art microarray technology, which allows scientists to easily identify, in a single experiment, hundreds or even thousands of genes. Project 3 researchers will employ this extraordinary technology to carry out microarray experiments for the entire group, especially in support of Projects 1 and 2 and will store and manage data for analysis. The researchers will also develop a cohesive microarray data analytical framework for the group
Project 4: Scaffolds to hold and mold progenitor cells at a site of tissue regeneration.
Jon Goldberg and Liisa Kuhn, principal investigators.
Most of the projects in the grant focus on particular kinds of tissues and learning how stem cells progress toward their final tissue types, including identification of the essential “signaling molecules” that direct the cells’ development, as well as other necessary environmental factors. As those questions are answered, the knowledge will be transferred to the biomaterials scaffolds project, where methods for practical clinical application will be developed.
Traditional reparative procedures for lost or damaged limbs use prosthetics, such as the implants used in a hip or knee replacement, made of metal, ceramic and plastic biomaterials. These prostheses are meant to replace the damaged tissue or organ, not to repair it. Cell-based therapies, on the other hand, require reabsorbable biomaterials. They must carry in the cells and define and shape the area of regeneration, but they must also degrade or reabsorb so that newly grown tissues can replace them. These types of biomaterials are called scaffolds and they are porous, like sponges, so that the cells can be contained inside the pores. Their purpose is to mimic the natural environment inside the body in which cells are accustomed to living. When biomaterials are made this way, they provide a means of triggering the cell to start regenerating the lost or damaged tissue. For the stem cell project, the biomaterials group will synthesize novel scaffolds designed specifically for musculoskeletal system regeneration.
Project 5: Optimizing mesoderm derived bone cell differentiation from hES cells.
David Rowe, principal investigator.
The project will give researchers who have experience working with mice stem cells directed to bone cell differentiation the opportunity to apply their knowledge to human embryonic stem cells. The research aims to provide objective criteria for evaluating the potential of cells to develop in bone tissue types with the goal of maximizing the potential to efficiently differentiate cells to produce bone tissue.
Project 6: Generation of bone via the neural crest development pathway. Mina Mina, principal investigator.
The cells that contribute to the facial skeleton, including the bones and teeth, are formed from cells of the cranial neural crest, the part of the embryonic ectoderm that develops into the skull, spine and associated nerves. There is a significant body of scientific evidence suggesting that differences in embryonic origin and mode of ossification, the natural formation of bones, in the bones of the face, skull and spine have significant influences on various properties of the skeletal tissues at those different sites. Consequently, effective cell-based therapies for skeletal tissues in the skull and face depend upon the capacity to identify and isolate stem cells capable of appropriately regenerating skeletal tissues. Project 6 aims to develop ways to generate and identify those cells.
Project 7: Generation of cartilage from hES derived progenitor cells.
Robert A. Kosher, principal investigator.
Degenerative diseases of cartilage are among the most prevalent and debilitating chronic health problems in the United States, and one of the main causes of decreased quality of life in adults. While more than 90 percent of the population over age 40 have some form of cartilage degeneration, treatment is particularly challenging because of the limited capacity of cartilage for self-repair and renewal. Human embryonic stem cells are a potentially powerful tool for repair of cartilage defects and one of the major goals of the Project 7 team is to develop culture systems and conditions that will allow stem cells to uniformly differentiate into chrondrocytes, cells that form cartilage.
Project 8: A mouse model to study the myogenic potential of hES cells.
David Goldhamer, principal investigator.
The long-term goal of Project 8 is to develop effective cell-based therapies for muscle degenerative diseases. Toward that end, the project has three interrelated objectives: 1) to evaluate the ability of human embryonic stem cells to repair skeletal muscle, 2) to further an understanding of muscle repair by defining the functions of two key factors that regulate stem cell differentiation, and 3) to develop a new repair model, using laboratory mice, to evaluate cell-based therapeutic outcomes.
Project 9. Correction of dermal lesions with hES derived progenitor cells.
Stephen Clark, principal investigator.
The goal of the project is to develop and test mice models utilizing human embryonic stem cells in the treatment of skin wounds. The work done in Project 9 is based on the hypothesis that embryonic stem cells can participate in and/or improve the skin wound healing process leading to a better resolution.