Ashley Allen

Ph.D. Defense Presentation

Wednesday, June 24, 2015, 9:00am
Petit Institute Suddath Seminar Room (IBB 1128)

Advisor
Robert E. Guldberg, Ph.D. (Georgia Institute of Technology)

Committee
Ian B. Copland, PhD. (Emory University)
Andrés J. García, Ph.D. (Georgia Institute of Technology)

Zulma Gazit, Ph.D. (Cedars-Sinai Medical Center)
Todd C. McDevitt, Ph.D. (Gladstone Institutes)

Modulation of Stem Cell Delivery Strategy by Platelet Lysate Utilization and Cell Aggregation for Enhanced Bone Regeneration

Large bone defects, such as those resulting from trauma or tumor resection, are repaired using graft tissue as the current gold standard. However, limitations of this treatment approach, including limited tissue availability and poor revascularization post-grafting, have motivated the development of cell- and protein-based strategies. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) is clinically utilized to promote bone repair in incidences of non-union, supra-physiologic dosing of rhBMP-2 can result in adverse effects including heterotopic bone formation and systemic inflammation. Mesenchymal stem cell (MSC)-based bone tissue engineering strategies offer several potential advantages over the use of osteoinductive protein alone. However, challenges to control delivered cell behavior remain a significant barrier to the clinical translation of MSC-based therapeutics.

Human platelet lysate (hPL) utilization and cell aggregation have each demonstrated the capacity to modulate a range of MSC outcomes, including cell number, phenotype, and secretome. The goal of this work was to investigate their potential application in MSC-based large bone defect repair. We pursued this objective through development of a bioluminescent cell tracking protocol and subsequent evaluation of these strategies for improved MSC survival and facilitated bone regeneration. Additional to engineering an efficacious MSC-based treatment for bone injury, this research aimed to relate key principles influencing cell-based tissue regeneration more globally.