"Engineering glycosaminoglycan coatings for mesenchymal stem cells-based cartilage tissue repair"

Jennifer Lei
PhD Candidate 

Advisor: Johnna S. Temenoff, PhD (Georgia Institute of Technology, Emory University)

Committee:
Edward A. Botchwey, PhD (Georgia Institute of Technology, Emory University)
Robert Guldberg, PhD (Georgia Institute of Technology)
Todd McDevitt, PhD (Georgia Institute of Technology, Emory University)
William Murphy, PhD (University of Wisconsin-Madison)

Mesenchymal stem cells (MSCs) have been implicated in stem cell therapies for tissue repair and regeneration because of their ability to differentiate into bone, cartilage, muscle, tendon, ligament, fat and other connective tissues, their ability to secrete bioactive molecules with trophic effects and their immunomodulatory properties when aggregated into small spheroids. One limitation of stem cell therapies is that there is minimal control over what soluble factors are being presented to the cells, making in vitro cellular differentiation variable and therefore resulting in a nonhomogeneous population of cell types. A second limitation of stem cell therapies is the loss of MSCs upon injection after 1-2 weeks. Cells are often are delivered with a material vehicle (i.e. scaffold or hydrogel) that facilitates retention at the injury site to prevent cell loss via clearance or dilution into surrounding fluids, however, this introduces extra volume of materials that can limit the number of cells delivered and interfere with defect closure over time.

Thus, the long term goal of this research is to develop an effective MSC-based therapy that maximizes therapeutic potential of cells to regenerate injured cartilage tissue. To achieve this, an injectable platform with sufficient flexibility to address obstacles of degenerated tissue matrix and inflammatory environments in cartilage disease and injury must be established. Therefore, the goal of this project is to implement a multilayer technology that coats MSCs with a molecule that will promote chondrogenic differentiation in vitro or cell retention in an ex vivo cartilage defect site. The rationale for this project is that using these ultrathin surface coatings on MSCs will allow for control over stem cell differentiation down a chondrogenic lineage and retention in a tissue defect site to facilitate integration of delivered cells with surrounding cartilage, ultimately overcoming the previously described limitations. The central hypothesis is that the multilayer coating will facilitate grafting of a negatively charged glycosaminoglycan or a heparin binding peptide sequence onto MSC spheroid surfaces, thus promoting chondrogenic differentiation in vitro and cell retention in cartilage defects.