The Effects of Progenitor Cells Combined with Scaffolds and Physiotherapy in Osteochondral Regenerative Medicine

Abstract

Articular cartilage has a limited capacity for self-repair Injury to cartilage often progresses to development of osteoarthritis (OA) The available medical interventions can help to relieve symptoms but fail to produce functional cartilage Recently the cell-based therapies for cartilage repair are mainly focused on chondrocytes mesenchymal stem cells (MSCs) or tissue specific progenitor cells Tissue-specific progenitor cells not only possess stem cell-like proliferative potential but also display tissue-specific phenotypes In the present study we investigated the osteochondral regeneration potential of two different kinds of progenitor cells The first are endothelial progenitor cells (EPCs) have proven to have a high capacity for regeneration and vasculogenesis in different tissues The second are cartilage stem/progenitor cells (CSPCs) which are resident cartilage-specific multipotent progenitor cells that have opened new avenues for cartilage repair The objectives of the current study included Part I (in vivo study): The investigation of the effects of an EPC loaded poly lactic-co-glycolic acid (PLGA) scaffold combined with continuous passive motion (CPM) on osteochondral defect repair in rabbits Part II-1 (in vitro study): To characterize CSPCs and compare them with osteoarthritis chondrocytes (OACs) and infrapatellar fat pad-derived stem cells (IFPs) through colony formation assay multilineage differentiation analysis gene expression analysis and biochemical analysis Part II-2 (in vivo study): To evaluate the osteochondral regeneration of the CSPC loaded PLGA scaffold during osteochondral defect repair in rabbits We found that the combination of CPM with EPC loaded PLGA scaffolds during the regenerative process could enhance the synthesis of cartilage specific matrix down-regulate subchondral bone formation and promote the synthesis of lubricin The EPCs offered a microenvironment for angiogenesis; whereas physical stimulation from CPM promoted tissue regeneration and host integration The characteristics of CSPCs are similar to those of MSCs and they have chondrogenic and osteogenic phenotypes without chemical induction Additionally CSPCs displayed a significantly higher synthesis of GAGs than OACs However there was no significantly different in gene expression of chondrogenesis with IFPs For in vivo study CSPC loaded PLGA scaffolds produced a hyaline-like cartilaginous tissue which showed good integration with host tissue and subchondral bone More importantly CSPCs involved the mechanism of the endochondral ossification of chondrocytes in the mineralization of the cartilage for promoting subchondral bone regeneration Overall this study demonstrated both CSPC and EPC progenitors had the potential to promote osteochondral regeneration The combination of these cell-based therapies might be beneficial for the repair of complex tissues such as osteochondral tissue

Date of Award	2019
Original language	English
Supervisor	Ming-Long Yeh (Supervisor)