Date of Award
Master of Science (MS)
Osteoarthritis (OA) is a leading cause of disability and pain to patients worldwide, and is characterized by abnormal subchondral bone remodeling, such as sclerosis and osteophyte formation, synovial tissue inflammation, and the destruction of articular cartilage, with limited capability for intrinsic repair. Currently, only palliative options are available to help treat the debilitating effects of the disease as there are no therapies authorized to halt or prevent the progression of OA. Due to the destructive nature of OA and a lack of current treatment options, there is an urgent need to develop novel therapies to mitigate the progression of OA.
Stem cell-based regenerative strategies hold promising opportunities to provide enhanced therapeutic efficacy due to their increasingly investigated and reported ability to regulate inflammation in vitro. Our lab has previously shown, in an in-vitro explant co-culture study, that human perinatal amniotic membrane-derived stem cells (hAMSCs) demonstrated an enhanced chondro-protective effect compared human adipose-derived stem cells (hADSCs), which are commonly utilized in regenerative applications. To further our previous findings, the overall purpose of this research was to investigate and compare the therapeutic efficacy of these two stem cell sources in mitigation of OA in vivo. This was achieved by directly comparing hAMSCs to hADSCs via various histological and biochemical outcome measures as well as longitudinal fluorescent cell tracking ensuing direct intra-articular injection into a spontaneous OA model; the Dunkin Hartley Guinea Pig (DHGP).
Results indicate that the DHGP serves as a validated spontaneous OA model while histological trends demonstrated that use of stem cell treatments mitigated cartilage degradation in comparison to non-stem cell treated groups. However, it was observed that both stem cell sources did not provide a significant therapeutic effect in vivo as results revealed a limited residence time and lack of tissue engraftment of hAMSCs and hADSCs following injection. Altogether, these findings highlight the current limitations of stem cell-based therapy once indicated in a complex, pathological environment. Therefore, further investigations are warranted to evaluate the therapeutic capabilities of stem cells following transplantation in in vivo models of OA.
Bowman, Mackenzie Catherine, "Comparing the Therapeutic Efficacy of Human Amniotic Membrane and Adipose-Derived Mesenchymal Stem Cells in Mitigation of Osteoarthritis" (2018). All Theses. 3250.