Abstract
Annulus fibrosus (AF) injuries can lead to substantial deterioration of intervertebral disc (IVD) which characterizes degenerative disc disease (DDD). However, treatments for AF repair/regeneration remain challenging due to the intrinsic heterogeneity of AF tissue at cellular, biochemical, and biomechanical levels. In this study, we isolated and characterized a sub-population of cells from rabbit AF tissue which formed colonies in vitro and could self-renew. These cells showed gene expression of typical surface antigen molecules characterizing mesenchymal stem cells (MSCs), including CD29, CD44, and CD166. Meanwhile, they did not express negative markers of MSCs such as CD4, CD8, and CD14. They also expressed Oct-4, nucleostemin, and SSEA-4 proteins. Upon induced differentiation they showed typical osteogenesis, chondrogenesis, and adipogenesis potential. Together, these AF-derived colony-forming cells possessed clonogenicity, self-renewal, and multi-potential differentiation capability, the three criteria characterizing MSCs. Such AF-derived stem cells may potentially be an ideal candidate for DDD treatments using cell therapies or tissue engineering approaches.
Highlights
As the major cause of low back pain which affects about 80% of the population, degenerative disc disease (DDD) has evolved into a serious medical problem and significantly contributes to healthcare costs [1]
Tissue engineering of annulus fibrosus (AF) mainly involve the use of AF cells [4,9,10], chondrocytes [5], or bone marrow stem cells (BMSCs) [3,6] of various origins
As a rule of thumb, mesenchymal stem cells (MSCs) from adult tissues tend to be tissue specific, meaning that MSCs originated from a certain tissue preferentially differentiate into the type of cells residing in this tissue [14,15,16,17]
Summary
As the major cause of low back pain which affects about 80% of the population, degenerative disc disease (DDD) has evolved into a serious medical problem and significantly contributes to healthcare costs [1]. Despite recent advancements [3,4,5,6], major challenge remains toward AF tissue engineering, mainly due to the tremendous complexity of AF tissue at cellular, biochemical, microstructural, and biomechanical levels [7,8]. Tissue engineering of AF mainly involve the use of AF cells [4,9,10], chondrocytes [5], or bone marrow stem cells (BMSCs) [3,6] of various origins. Use of BMSCs, which have been overwhelmingly used and shown effectiveness in AF tissue engineering, confronts with a problem of limited cell availability (only 0.001–0.01% BMSCs in bone marrow aspirates or marrow tissue) [13]. Seeking new cell sources for AF tissue engineering appears to be necessary
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