Date of Award

5-2016

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Committee Member

Dr. Jeremy Mercuri, Committee Chair

Committee Member

Dr. Ann Foley

Committee Member

Dr. John Tokish

Committee Member

Dr. Ken Webb

Abstract

Diseases affecting the cartilage and/or bone, including osteoarthritis (OA), are the most prevalent musculoskeletal tissue pathologies. OA is the result of cartilage degradation, altered sub-chondral bone, impaired joint mobility and severe pain - making it one of the leading causes of disability worldwide. While OA is stereotypically described as a physical wear and tear disease, mounting evidence suggests that synovial inflammation significantly contributes to its pathogenesis. In OA, macrophages infiltrate the synovium and secrete supra-physiological levels of pro-inflammatory cytokines, which create a caustic joint environment promoting articular cartilage degradation. Due to the pro-inflammatory characteristics of OA, the immunomodulatory potential of stem cells likely represents an under investigated therapeutic alternative. The purpose of this research was to investigate if stem cells from the amniotic membrane (a tissue routinely discarded after the birth of term pregnancies) represent an efficacious alternative cell source for future OA therapies. This was achieved by directly comparing the abilities of human amniotic membrane derived stem cells and a commonly employed stem cell, human adipose derived stem cells, with regards to osteogenic and chondrogenic differentiation potential as well as the ability to mitigate OA disease progression both ex vivo and in vivo. Our results demonstrate stem cells from the amniotic membrane exhibit heightened differentiation potential, higher yields, enhanced immunomodulatory properties, and the ability to induce pro-regenerative (M2) phenotypes within macrophages, in OA experimental models. Additionally, amnion stem cells appeared to offer accelerated treatment time lines compared to adipose derived stem cells. For these reasons, we believe amnion membrane derived stem cells are an efficacious stem cell source for OA therapeutic approaches.

Share

COinS