Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing

Stem Cells Transl Med. 2014 Mar;3(3):387-94. doi: 10.5966/sctm.2012-0170. Epub 2014 Jan 21.

Abstract

Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. In this study, we report a new strategy of articular cartilage protection by intra-articular injection of novel human meniscus stem/progenitor cells (hMeSPCs). We found that hMeSPCs displayed both mesenchymal stem cell characteristics and high expression levels of collagen II. In the rat meniscus injury model, hMeSPC transplantation not only led to more neo-tissue formation and better-defined shape but also resulted in more rounded cells and matured extracellular matrix. Stromal cell-derived factor-1 (SDF-1) enhanced the migration of hMeSPCs, whereas AMD3100 abolished the chemotactic effects of SDF-1 on hMeSPCs, both in vitro and in vivo. In an experimental OA model, transplantation of hMeSPCs effectively protected articular cartilage, as evidenced by reduced expression of OA markers such as collagen I, collagen X, and hypoxia-inducible factor 2α but increased expression of collagen II. Our study demonstrated for the first time that intra-articular injection of hMeSPCs enhanced meniscus regeneration through the SDF-1/CXCR4 axis. Our study highlights a new strategy of intra-articular injection of hMeSPCs for meniscus regeneration.

Keywords: Cell transplantation; Meniscus injury; Meniscus-derived stem/progenitor cells; Osteoarthritis; Regeneration; SDF-1/CXCR4 axis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cartilage, Articular / injuries
  • Cartilage, Articular / metabolism
  • Cartilage, Articular / pathology
  • Chemokine CXCL12 / genetics*
  • Chemokine CXCL12 / pharmacology
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type II / genetics
  • Collagen Type II / metabolism
  • Collagen Type X / genetics
  • Collagen Type X / metabolism
  • Gene Expression
  • Heterocyclic Compounds / pharmacology
  • Humans
  • Injections, Intra-Articular
  • Male
  • Menisci, Tibial / metabolism
  • Menisci, Tibial / pathology
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism
  • Osteoarthritis / genetics
  • Osteoarthritis / pathology
  • Osteoarthritis / therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, CXCR4 / genetics*
  • Receptors, CXCR4 / metabolism
  • Regeneration / physiology*
  • Signal Transduction
  • Tibial Meniscus Injuries
  • Transplantation, Heterologous

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • CXCL12 protein, human
  • CXCR4 protein, human
  • Chemokine CXCL12
  • Collagen Type I
  • Collagen Type II
  • Collagen Type X
  • Heterocyclic Compounds
  • Receptors, CXCR4
  • endothelial PAS domain-containing protein 1
  • plerixafor