Intervertebral Disc-Derived Stem/Progenitor Cells as a Promising Cell Source for Intervertebral Disc Regeneration

Hindawi Stem Cells International Volume 2018, Article ID 7412304, 11 pages https://doi.org/10.1155/2018/7412304 Review Article Intervertebral Disc-Derived Stem/Progenitor Cells as a Promising Cell Source for Intervertebral Disc Regeneration Binwu Hu,1 Ruijun He ,1 Kaige Ma ,1 Zhe Wang,1 Min Cui ,1 Hongzhi Hu,1 Saroj Rai,1,2 Baichuan Wang ,1 and Zengwu Shao 1 1 Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China 2 National Trauma Center, National Academy of Medical Sciences, Kathmandu, Nepal Correspondence should be addressed to Baichuan Wang; and Zengwu Shao; Received 24 May 2018; Revised 18 October 2018; Accepted 5 November 2018; Published 18 December 2018 Academic Editor: Frederic Deschaseaux Copyright © 2018 Binwu Hu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Intervertebral disc (IVD) degeneration is considered to be the primary reason for low back pain. Despite remarkable improvements in both pharmacological and surgical management of IVD degeneration (IVDD), therapeutic effects are still unsatisfactory. It is because of the fact that these therapies are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD. Accumulating evidence has revealed that the endogenous stem/progenitor cells exist in the IVD, and these cells might be a promising cell source in the regeneration of degenerated IVD. However, the biological characteristics and potential application of IVD-derived stem/progenitor cells (IVDSCs) have yet to be investigated in detail. In this review, the authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVD. The authors believe that this review exclusively address the current understanding of IVDSCs and provide a novel approach for the IVD regeneration. 1. Introduction Low back pain (LBP) is one of the most common musculoskeletal disorders causing a tremendous socioeconomic burden to the patients due to lost productivity and increasing health care costs [1–3]. Although numerous and complex causes are involved in the pathogenesis of LBP, the intervertebral disc (IVD) degeneration appears to be the foremost cause [4, 5]. However, established treatments of IVD degeneration (IVDD), including medical and surgical treatments, are mainly focused on alleviating the symptoms rather than treating the underlying cause or restoring the structure and biomechanical function of the IVD [6–8]. The loss of disc cell viability and functionality plays a critical role in disturbing disc homeostasis, which reduces biosynthesis of extracellular matrix (ECM) components and triggers the IVDD [9, 10]. Therefore, cell-based therapy and regenerative medicine aiming at restraining or even reverting the loss of disc cell number and function have attracted much attention in the field of IVD regeneration [11]. Currently, a number of therapeutic modalities, such as growth factor supply, gene therapy and the delivery of functional cells, have been developed in order to rescue the disc cells [12–15]. Of these, the delivery of functional cells is, possibly, a promising therapeutic strategy. Many different kinds of functional cells from different areas of the body, i.e., nucleus pulposus cells (NPCs), bone marrow mesenchymal stem cells (BMSCs), adipose stem cells (ASCs), muscle-derived stem cells, synovial stem cells, induced pluripotent stem cells, olfactory neural stem cells, hematopoietic stem cells, and embryonic stem cells, can be successfully transplanted into the IVD with a hope to repair or regenerate the IVD [16]. Owing to wide availability and multilineage differentiation potential, the stem cells (SCs) have been extensively used and have shown 2 a promising result in animal models and clinical trials [17, 18]. However, some obstacles are always hindering the further application of SCs in disc regeneration. These problems include puncture injury during SC extraction from the tissues and formation of osteophytes in the degenerated disc due to the leakage of SCs [19, 20]. Moreover, the microenvironment of IVD is characterized by excessive mechanical loading, high osmolarity, limited nutrition, acidic pH, and low oxygen tension [21–23]. Such microenvironment might impair the viability, proliferation, and ECM biosynthesis abilities of transplanted SCs leading to a limited repair potential [21–23]. Thus, it is desperately necessary to identify novel cell sources for IVD regeneration. Many tissues have been identified to contain adult tissuespecific SCs, also known as endogenous SCs [24–26]. These endogenous SCs are capable of balancing the homeostasis of the tissues by regulating their own proliferation and differentiation. Therefore, endogenous stem/progenitor cells are regarded as a promising cell source for regenerating tissues because of the potential of overcoming the obstacles related to cell transplantation [24]. The IVD is the largest avascular structure in the body, which has been previously thought to have a little or poor self-repair capacity in adult mammals [27]. Nevertheless, many previous studies have indicated that the resident SCs exist both in normal and degenerated IVD and are referred to as IVD-derived stem/progenitor cells (IVDSCs) [28–31]. These cells can be isolated from different compartments of IVD, including nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplate (CEP) and can express most of the phenotype markers that define MSCs [29, 32–36]. Furthermore, it is also proven that there exists SC niche (SCN) within the IVD, which is confined around the perichondrium region adjacent to the epiphyseal plate (EP) and outer zone of the AF [6, 27]. Thus, promoting self-repair via mobilizing the endogenous SCs might be a prospective approach for stem cell-based therapy and the IVD regeneration. However, as a novel cell subset in IVD, our knowledge about IVDSCs remains largely limited. Therefore, authors aim to perform a review to systematically discuss (1) the isolation, surface markers, classification, and biological characteristics of IVDSCs; (2) the aging- and degeneration-related changes of IVDSCs and the influences of IVD microenvironment on IVDSCs; and (3) the potential for IVDSCs to promote regeneration of degenerated IVDSCs. The authors believe that this review exclusively addresses the current understanding of IVDSCs and provides a novel approach for the IVD regeneration. 2. Identification of IVDSCs In 2007, Risbud et al. identi (...truncated)