Intra-articular injection of human meniscus stem/progenitor cells promotes meniscus regeneration and ameliorates osteoarthritis through stromal cell-derived factor-1/CXCR4-mediated homing.
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.
Center for Stem Cell and Tissue Engineering, Department of Orthopedic Surgery, Second Affiliated Hospital, and Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule, Zurich, Switzerland.
Weiliang
W
Shen
Jialin
J
Chen
Ting
T
Zhu
Longkun
L
Chen
Wei
W
Zhang
Zhi
Z
Fang
Boon Chin
BC
Heng
Zi
Z
Yin
Xiao
X
Chen
Junfeng
J
Ji
Weishan
W
Chen
Hong-Wei
HW
Ouyang
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D001596:Benzylamines; D002358:Cartilage, Articular / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000494:pharmacology; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D024121:Collagen Type X / Q000235:genetics / Q000378:metabolism; D000080027:Cyclams; D015870:Gene Expression; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008592:Menisci, Tibial / Q000378:metabolism / Q000473:pathology; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D010003:Osteoarthritis / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction; D000070600:Tibial Meniscus Injuries; D014183:Transplantation, Heterologous; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D001596:Benzylamines; D054377:Chemokine CXCL12; D024042:Collagen Type I; D024043:Collagen Type II; D024121:Collagen Type X; D000080027:Cyclams; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D000099162:Endothelial PAS Domain-Containing Protein 1; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; C088327:plerixafor
Cell transplantation; Meniscus injury; Meniscus-derived stem/progenitor cells; Osteoarthritis; Regeneration; SDF-1/CXCR4 axis