Degenerative joint disease or osteoarthritis (OA) is a group of mechanical abnormalities involving degradation of joints, including articular cartilage and subchondral bone. According to the National Arthritis Data Workgroup, OA affected 26.9 million adults in 2005 in the United States, and the number is projected to increase up to 40% by 2030, therefore making joint surface restoration a priority. None of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets functional demands placed upon this tissue in vivo.
We hypothesized that human pluripotent stem cell (PSC) derived chondroprogenitor cells (ChPC) or the precursors of ChPC may have greater potential for use in regenerative medicine than adult articular chondrocytes or adult mesenchymal stem cells based on their chondrogenic commitment, lineage potential and proliferative ability.
Further we propose that studies to identify and characterize the stages of human chondrogenesis are needed to insure successful generation and isolation of identical ChPC from PSC.
Thus, the overall goal of the proposed study is to define the stages through which ChPC are generated from multipotent mesodermal ancestors, with the ultimate objective of producing ChPC with the highest potential for use in regenerative medicine.
Our group has recently reported the earliest embryonic mesodermal progenitor (EMP) produced during human PSC differentiation. EMPs are ancestors of more lineage restricted mesenchymal progenitor cells (osteo- and chondrogenic), hematoendothelial and cardiovascular progenitors. We will use this novel EMP population to recapitulate early stages of embryonic mesenchyme generation, chondrogenesis and eventually, articular cartilage formation. We also carried out pilot immunophenotypical characterization of primary ChPC at early stages of human embryogenesis. In combination with in vitro studies of primary and induced PSC (iPSC)-derived ChPC populations, a xenograft animal model and in vivo bioluminescence imaging will be utilized in the following specific aims to study the potential of iPSC-derived ChPC for use in regenerative medicine.