Mesenchymal Stem Cell in the Intervertebral Disc

Degeneration of the intervertebral disc (IVD) is a major spinal disorder that causes back pain. Nucleus pulposus (NP) in the central of IVD dehydrates and become more fibrous in the IVD degeneration. NP cells undergo apoptosis with the degeneration of extracellular matrix (ECM) components. To replenish the NP cells and core ECM, bone marrow mesenchymal stromal cells (BMSCs) have been highlighted in the regeneration of IVD degeneration. BMSCs differentiate into NP-like cells with the secretion of ECM components, which may not only replenish the number of NP cells but also stimulate NP reconstruction. This further maintains tissue homeostasis. Up to date, the disc progenitor cells (DPCs) have been identified with the characteristics of multidifferentiation and stem cell phenotype. These cells are involved in the IVD diseases and show regenerative potentials. However, the differences between the BMSCs and DPCs remain elusive, in particular, the cellular connection in vivo. As such, this chapter will discuss the findings of the two cell types and propose a novel concept in the understanding of the biology of IVD

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Identification and characterization of stem cell-like populations in primate intervertebral disc

Upon aging, the intervertebral disc (IVD) inevitably undergoes degeneration characterized by biochemical and morphologic changes. IVD degeneration can lead to multiple clinical disorders such as back and neck pain, and myelopathy. Low back pain can disable up to 85% of the adult population and results in a significant restriction of social activities and inability to work. Such disorder incurs billions of dollars in medical expenditures each year. Despite advances in the detection and treatment of the degeneration, the regeneration of the IVD remains low because current therapies are limited by exogenous curing approaches. New strategies for the reversal of IVD degeneration, including gene, cytokine, and stem cell therapies that can influence the anabolic and catabolic pathways in disc cells have been under investigation. These therapies aim to rejuvenate or replace diminished nucleus pulposus cells in the degenerative IVD. Recent reports have put forth a proposal of “endogenous disc stem cells”, suggesting that cells derived from the degenerative IVD tissue possess stem cell properties. These putative stem cells are believed to regulate the development and homeostasis of the IVD tissue. In this study, we identified and characterized a stem cell population from the IVD of healthy Rhesus monkey, termed disc stem/progenitor cells (DSCs). We show that the DSCs possess clonogenicity, multipotency and self-renewal capacity. The DSCs are phenotypically similar to bone marrow mesenchymal stem cells (BMSCs) but they are not identical. The DSCs show a faster growth rate under hypoxia than normoxia. DSCs derived from nucleus pulposus (DSCNP) show a stable expression level of hypoxia inducible factor-1 alpha (Hif-1ａ) in response to hypoxia. DSCs derived from annulus fibrosus (DSCAF) are more resistant to apoptosis under hypoxia than DSCNP. More importantly, small leucine-rich proteoglycans (SLRPs) are identified as important DSC niche components. We show that biglycan (bgn) and decorin (dcn) reduce the susceptibility of DSCs to hypoxia-induced apoptosis by promoting the expression of hypoxia inducible factors (HIFs). Our findings suggest that DSCs rely on the unique niche components for survival. In summary, our findings propose the existence of endogenous stem cells in IVD. Further study of the DSCs may provide new insights into the biology of IVD and facilitate the design of new strategies to treat disc degeneration in future.published_or_final_versionOrthopaedics and TraumatologyDoctoralDoctor of Philosoph

Polydopamine-Assisted Surface Modification for Bone Biosubstitutes

Polydopamine (PDA) prepared in the form of a layer of polymerized dopamine (DA) in a weak alkaline solution has been used as a versatile biomimetic surface modifier as well as a broadly used immobilizing macromolecule. This review mainly discusses the progress of biomaterial surface modification inspired by the participation of PDA in bone tissue engineering. A comparison between PDA-assisted coating techniques and traditional surface modification applied to bone tissue engineering is first presented. Secondly, the chemical composition and the underlying formation mechanism of PDA coating layer as a unique surface modifier are interpreted and discussed. Furthermore, several typical examples are provided to evidence the importance of PDA-assisted coating techniques in the construction of bone biosubstitutes and the improvement of material biocompatibility. Nowadays, the application of PDA as a superior surface modifier in multifunctional biomaterials is drawing tremendous interests in bone tissue scaffolds to promote the osteointegration for bone regeneration

Insight into Biological Apatite: Physiochemical Properties and Preparation Approaches

Biological apatite is an inorganic calcium phosphate salt in apatite form and nano size with a biological derivation. It is also the main inorganic component of biological hard tissues such as bones and teeth of vertebrates. Consequently, biological apatite has a wide application in dentistry and orthopedics by using as dental fillers and bone substitutes for bone reconstruction and regeneration. Given this, it is of great significance to obtain a comprehensive understanding of its physiochemical and biological properties. However, upon the previous studies, inconsistent and inadequate data of such basic properties as the morphology, crystal size, chemical compositions, and solubility of biological apatite were reported. This may be ascribed to the differences in the source of raw materials that biological apatite are made from, as well as the effect of the preparation approaches. Hence, this paper is to provide some insights rather than a thorough review of the physiochemical properties as well as the advantages and drawbacks of various preparation methods of biological apatite

The Regulatory Roles of MicroRNAs in Bone Remodeling and Perspectives as Biomarkers in Osteoporosis

MicroRNAs are involved in many cellular and molecular activities and played important roles in many biological and pathological processes, such as tissue formation, cancer development, diabetes, neurodegenerative diseases, and cardiovascular diseases. Recently, it has been reported that microRNAs can modulate the differentiation and activities of osteoblasts and osteoclasts, the key cells that are involved in bone remodeling process. Meanwhile, the results from our and other research groups showed that the expression profiles of microRNAs in the serum and bone tissues are significantly different in postmenopausal women with or without fractures compared to the control. Therefore, it can be postulated that microRNAs might play important roles in bone remodeling and that they are very likely to be involved in the pathological process of postmenopausal osteoporosis. In this review, we will present the updated research on the regulatory roles of microRNAs in osteoblasts and osteoclasts and the expression profiles of microRNAs in osteoporosis and osteoporotic fracture patients. The perspective of serum microRNAs as novel biomarkers in bone loss disorders such as osteoporosis has also been discussed