Restoring Osteochondral Defects through the Differentiation Potential of Cartilage Stem/Progenitor Cells Cultivated on Porous Scaffolds.

Tzu-Hsiang Lin,Che-Chia Hsu,Ming-Long Yeh,Hsueh-Chun Wang

doi:10.3390/cells10123536

Abstract

Cartilage stem/progenitor cells (CSPCs) are cartilage-specific, multipotent progenitor cells residing in articular cartilage. In this study, we investigated the characteristics and potential of human CSPCs combined with poly(lactic-co-glycolic acid) (PLGA) scaffolds to induce osteochondral regeneration in rabbit knees. We isolated CSPCs from human adult articular cartilage undergoing total knee replacement (TKR) surgery. We characterized CSPCs and compared them with infrapatellar fat pad-derived stem cells (IFPs) in a colony formation assay and by multilineage differentiation analysis in vitro. We further evaluated the osteochondral regeneration of the CSPC-loaded PLGA scaffold during osteochondral defect repair in rabbits. The characteristics of CSPCs were similar to those of mesenchymal stem cells (MSCs) and exhibited chondrogenic and osteogenic phenotypes without chemical induction. For in vivo analysis, CSPC-loaded PLGA scaffolds produced a hyaline-like cartilaginous tissue, which showed good integration with the host tissue and subchondral bone. Furthermore, CSPCs migrated in response to injury to promote subchondral bone regeneration. Overall, we demonstrated that CSPCs can promote osteochondral regeneration. A monophasic approach of using diseased CSPCs combined with a PLGA scaffold may be beneficial for repairing complex tissues, such as osteochondral tissue.

Highlights

Articular cartilage has a limited capacity for self-repair and injury to the cartilage often progresses to osteoarthritis (OA) development [1]
A monophasic approach of using diseased Cartilage stem/progenitor cells (CSPCs) combined with a poly(lactic-co-glycolic acid) (PLGA) scaffold may be beneficial for repairing complex tissues, such as osteochondral tissue
We examined the depth of CSPC migration in vivo

Summary

Introduction

Articular cartilage has a limited capacity for self-repair and injury to the cartilage often progresses to osteoarthritis (OA) development [1]. Available medical interventions such as autologous chondrocyte implantation (ACI) [2], microfracture and mosaicplasty [3]. Cell-based therapies for cartilage repair have mainly focused on chondrocytes [4], mesenchymal stem cells (MSCs) such as adipose derived stem cells [5] and bone marrow-derived stem cell [6], or tissue-specific progenitor cells [7]. MSCs have been substituted for chondrocytes in osteochondral repair because of their rapid proliferation and multipotency characteristics [10]. The innate multilineage differentiation of MSCs [11] leads to the risk of hypertrophic growth [12] and endochondral ossification [13]

Methods

Discussion

Conclusion