Victor Y L Leung

Victor Y L Leung
The University of Hong Kong | HKU · Department of Orthopaedics and Traumatology

PhD

About

93
Publications
30,110
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Introduction

Publications

Publications (93)
Article
Full-text available
A growing body of evidence in humans and animal models indicates an association between intervertebral disc degeneration (IDD) and increased fibrotic elements in the nucleus pulposus (NP). These include enhanced matrix turnover along with the abnormal deposition of collagens and other fibrous matrices, the emergence of fibrosis effector cells, such...
Article
Full-text available
Defective biosynthesis or function of proteoglycans causes pathological conditions in a variety of tissue systems. Osteoarthritis (OA) is a prevalent degenerative joint disorder characterized by progressive cartilage destruction caused by imbalanced proteoglycan synthesis and degradation. Identifying agents that regulate proteoglycan metabolism may...
Article
Full-text available
Mice have been increasingly used as preclinical model to elucidate mechanisms and test therapeutics for treating intervertebral disc degeneration (IDD). Several intervertebral disc (IVD) histological scoring systems have been proposed, but none exists that reliably quantitate mouse disc pathologies. Here, we report a new robust quantitative mouse I...
Article
Full-text available
Background Aberrant mechanical loading of the spine causes intervertebral disc (IVD) degeneration and low back pain. Current therapies do not target the mediators of the underlying mechanosensing and mechanotransduction pathways, as these are poorly understood. This study investigated the role of the mechanosensitive transient receptor potential va...
Article
Full-text available
Intervertebral disc degeneration (IDD), a major cause of low back pain, occurs with ageing. The core of the intervertebral disc, the nucleus pulposus (NP), embedded in a proteoglycan‐rich and gelatinous matrix, is derived from the embryonic notochord. With IDD, the NP becomes fibrous, containing fewer cells, which are fibroblastic and of unknown or...
Article
Full-text available
Intervertebral disc degeneration might be amenable to stem cell therapy, but the required cells are scarce. Here, we report the development of a protocol for directed in vitro differentiation of human pluripotent stem cells (hPSCs) into notochord-like and nucleus pulposus (NP)-like cells of the disc. The first step combines enhancement of ACTIVIN/N...
Conference Paper
Introduction: Depletion of extracellular matrix producing nucleus pulposus (NP) cells in intervertebral disc (IVD) degeneration limits the self-repair ability per se. Currently, tyrosine kinase receptor 2 (Tie2) and disialoganglioside 2 (GD2) expressing progenitor cells were identified in human adult NP tissue based on in vitro clonogenicity and in...
Article
Full-text available
Transient receptor potential (TRP) channels have emerged as potential sensors and transducers of inflammatory pain. The aims of this study were to investigate (1) the expression of TRP channels in intervertebral disc (IVD) cells in normal and inflammatory conditions and (2) the function of Transient receptor potential ankyrin 1 (TRPA1) and Transien...
Article
Intervertebral disc (IVD) degeneration is associated with low back pain. In IVDs, a high mechanical load, high osmotic pressure and hypoxic conditions create a hostile microenvironment for resident cells. How IVD homeostasis and function are maintained under stress remains to be understood; however, several research groups have reported isolating n...
Article
Intervertebral disc (IVD) degeneration (IDD) is considered as one of the major causes for low back pain (LBP). However, conventional surgical approaches for treating LBP do not aim to counter the degeneration. Biological interventions have been investigated with an attempt to regenerate the IVD by restoring its matrices and cell activities. This re...
Article
Full-text available
PurposeFresh frozen intervertebral disc allograft transplantation has been reported to be a viable treatment option for advanced degenerative disc diseases, but rapid degeneration of the postoperative allograft was found. Loss of nutrient supply is believed to be the most likely inducer because the disc allografts have to endure in an ischaemic env...
Article
Full-text available
Purpose Fresh-frozen intervertebral disc (IVD) allograft transplantation has been successfully performed in the human cervical spine. Whether this non-fusion technology could truly decrease adjacent segment disease is still unknown. This study evaluated the long-term mobility of the IVD-transplanted segment and the impact on the adjacent spinal seg...
Article
Bone morphogenetic proteins (BMPs) play roles in promoting cell anabolism, especially extracellular matrix production. The difference between BMP members in their capacity to modulate intervertebral disc cell activity is yet to be defined. BMP-7/OP-1 has been shown to retard disc degeneration. We compared the activity of BMP-7 with BMP-2 on nucleus...
Article
A new scoring system based on histo-morphology of mouse intervertebral disc (IVD) was established to assess changes in different mouse models of IVD degeneration and repair. IVDs from mouse strains of different ages, transgenic mice, or models of artificially induced IVD degeneration were assessed. Morphological features consistently observed in no...
Article
Full-text available
Background Ligamentum flavum (LF) hypertrophy is a common cause of lumbar spinal stenosis and is thought to be degeneration-driven. Developmental spinal stenosis (DSS) is characterized by pre-existing narrowed spinal canals and is likely a developmental problem that occurs in childhood. In these cases, the LF may demonstrate different characteristi...
Article
Full-text available
Previous human study suggested that fresh-frozen intervertebral disc allograft transplantation can relieve neurological symptoms and restore segmental kinematics. Before wide clinical application, research into the pathophysiology of the postoperative disc allograft is needed. One important question that remains to be answered in disc allografting...
Article
Full-text available
Nucleus pulposus (NP) cells of the intervertebral disc are essential for synthesizing extracellular matrix that contributes to disc health and mechanical function. NP cells have a unique morphology and molecular expression pattern derived from their notochordal origin, and reside in N-cadherin (CDH2) positive cell clusters in vivo. With disc degene...
Article
Intervertebral discs (IVDs) degeneration are responsible for the majority of cases of low back pain, which affects millions of people worldwide. Current clinical therapies for degenerative disc diseases (DDD) involve medications or physiotherapy for mild to moderate degeneration, and surgeries for severe degeneration. However, current treatments ai...
Article
Objective: Recent evidence suggests a role of fibrogenesis in intervertebral disc (IVD) degeneration. We aim to explore if fibrotic genes may serve as IVD degeneration indicators, and if their expression is associated with myofibroblast activity. Design: Transcriptional expression of fibrosis markers (COL1A1, COL3A1, FN1, HSP47, MMP12, RASAL1) w...
Article
Like articular joints, intervertebral discs (IVD) suffer from degeneration which is thought to be irreversible after initiation. Disc degeneration is associated with low back pain, and the degenerative IVD can be a source of irritation. While the cause of IVD degeneration is not entirely understood to date, both genetic and environmental factors ha...
Article
Nucleus pulposus (NP), the gelatinous tissue core in the intervertebral disc (IVD), is enriched with extracellular matrix type II collagen (encoded by COL2A1) and aggrecan (encoded by AGC1). Dysregulation of extracellular matrix proteins in the NP is tightly associated with disc degeneration, ultimately leading to a loss of mechanical function in m...
Article
Low back pain (LBP) affects 80% of the whole population around the world and causes great social-economic burden. Intervertebral disc (IVD) degenerates with aging and is a major contribution to LBP. Mature NP (nucleus pulposus, the center part of IVD) cells are similar to, but not the same as, chondrocytes. The search for NP markers has prompted th...
Article
Full-text available
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 o...
Article
Intervertebral disc (IVD) degeneration is the most common cause of low back pain, which affect 80% of the population during their lives, with heavy economic burden. Many factors have been demonstrated to participate in IVD degeneration. In this study, we investigated the role of SHOX2 in the development of IVD degeneration. First, we detected the e...
Article
Transforming growth factor-β (TGF-β) has been demonstrated as a potential therapeutic target in osteoarthritis. However, beneficial effects of TGF-β supplement and inhibition have both been reported, suggesting characterization of the spatiotemporal distribution of TGF-β during the whole time course of osteoarthritis is important. To investigate th...
Article
The intervertebral disc (IVD) is responsible for normal spinal motion and load distribution. However, degeneration may occur due to age- and non-age-related processes and is primarily characterized by a reduction in the number of chondrocyte-like cells and abnormal extracellular matrix (ECM) structure in the nucleus pulposus. Although IVD progenito...
Article
Full-text available
Reverse-transcription quantitative PCR (RT-qPCR) is a powerful technique for quantification of gene expression. Extraction of RNA directly from human and large animal intervertebral disc (IVD) tissue is technically challenging due to its tough nature, low cell-to-matrix ratio and high proteoglycan content. IVD is consisted of nucleus pulposus (NP)...
Article
Differences in matrix compositions in human nucleus pulposus (NP) clinical samples demand different cell isolation protocols for optimal results but there is no clear guide about this to date. Sub-optimal protocols may result in low cell yield, limited reliability of results or even failure of experiments. Cell yield, viability and attachment of ce...
Article
Intervertebral disc degeneration is associated with a malfunction of the nucleus pulposus (NP). Alginate culturing provides a favorable microenvironment for the phenotypic maintenance of chondrocyte-like NP cells. However, NP cells are recently evidenced to present heterogeneous populations, including progenitors, fibroblastic cells and primitive N...
Article
Full-text available
Intervertebral disc degeneration is a common spinal disorder and may manifest with low back pain or sciatica. The degeneration is characterized by the loss of extracellular matrix integrity and dehydration in the nucleus pulposus. This compromises the viscoelastic property and compressive strength of the disc and therefore the capacity to withstand...
Data
Mathematically removing the nucleic acid concentration overestimation caused by phenol contamination About the article "Correction for concentration overestimation of nucleic acids with phenol" published in Analytical Biochemistry Volume 465, 15 November 2014, Pages 179–186 http://www.sciencedirect.com/science/article/pii/S000326971400339X
Article
The skin is the body's largest organ and it is able to self-repair throughout an individual's life. With advanced age, skin is prone to degenerate in response to damage. Although cosmetic surgery has been widely adopted to rejuvinate skin, we are far from a clear understanding of the mechanisms responsible for skin aging. Recently, adult skin-resid...
Article
We report a computational method based on UV spectra for correcting the overestimated concentrations of nucleic acid samples contaminated with TRIzol/ phenol. The derived correction formulas were validated using RNA solutions, double stranded DNA solutions and single stranded oligonucleotide solutions. RT-qPCR with SYBR green was performed to asses...
Article
Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the aetiology remains unclear. Here, we show that disc degeneration exhibits features of fibr...
Article
Full-text available
Intervertebral disc degeneration is associated with low back pain. Mesenchymal stem cells (MSCs) have been used to "regenerate" the disc. The aim of this study was to perform a systematic review of comparative controlled studies assessing the safety and efficacy of using MSCs in animal in disc regeneration. Literature databases were extensively sea...
Article
Full-text available
A major hurdle of cellular therapy for biological treatment of intervertebral disk (IVD) degeneration is the delivery method where current delivery methods are limited to intradiscal injection which can potentially cause further degeneration. Recent studies indicated that multipotential stem cells (MPSCs) from human umbilical cord blood home to inj...
Article
The concept of mesenchymal stem cells (MSCs) is becoming increasingly obscure due to the recent findings of heterogeneous populations with different levels of stemness within MSCs isolated by traditional plastic-adherence. MSCs were originally identified in bone marrow and later detected in many other tissues. Currently, no cloning based on single...
Poster
Full-text available
Introduction Biomimetic scaffolds have been implicated in tissue engineering. They have been shown superior in inducing stem cell differentiation or promoting native cell phenotype. We have investigated the use of native tissue as biomimetic scaffold in nucleus pulposus (NP) cell engineering for regeneration. We hypothesized that the NP phenotype c...
Article
Introduction Integrity of the nucleus pulposus (NP) has been implicated in the function and homeostasis of intervertebral disc (IVD). Understanding the regulation of NP cells would contribute to their engineering and development of therapeutics for treating IVD degeneration. Studies in mouse models indicate that early events of IVD degeneration inv...
Article
Introduction A previous human study suggested that intervertebral disc allograft transplantation in the cervical spine can relieve neurological symptoms and restore segmental kinematics. We have demonstrated that lumbar intervertebral disc transplantation could restore the global and segmental mobility after 12 months using a goat model. However, t...
Article
Introduction Intervertebral disc degeneration is associated with low back pain. Mesenchymal stem cells (MSCs) have been used to halt the progression or regenerate the disc with hopes to prevent or treat discogenic back pain. However, the safety and efficacy of the use of MSCs for such treatment in animal and human models at short- and long-term ass...
Article
Introduction Nucleus pulposus (NP) is the center and major compartment of intervertebral disc (IVD). Mesenchymal stem cells (MSCs) are a type of stem cell source under intensive investigation for their potential to regenerate NP. MSCs have been identified from various sources with different characteristics. There are indications that fetal or close...
Article
Introduction Intervertebral disc (IVD) degeneration leads to loss of mechanical function of motion segment and is attributed to deregulated extracellular matrix components in the nucleus pulposus (NP). The NP is rich in type II collagen (encoded by COL2A1) and aggrecan (encoded by AGC1), which are known to be regulated by the master chondrogenic tr...
Poster
Introduction Intervertebral disc (IVD) degeneration is associated with low back pain which affects millions of people worldwide. The understanding of the phenotype of nucleus pulposus (NP) cells is important to assessing disc degeneration progression as well as evaluating methodologies that aim to regenerate the disc. Microarray followed by confir...
Article
Full-text available
Mesenchymal stem cells (MSCs) have the potential to treat early intervertebral disc (IVD) degeneration. However, during intra-discal injection, the vast majority of cells leaked out even in the presence of hydrogel carrier. Recent evidence suggests that annulus puncture is associated with cell leakage and contributes to osteophyte formation, an und...
Article
Full-text available
Intervertebral disc degeneration usually starts from the inner nucleus pulposus (NP). The majority of previous NP-related studies assessed the outcome by the expression of chondrogenic markers since NP cells are chondrocyte like. However, NP cells are unique from chondrocytes and such assessments may be inappropriate. Very recently, several investi...
Article
Degeneration of the intervertebral disc (IVD) is a major spinal disorder that associates with neck and back pain. Recent studies of clinical samples and animal models for IVD degeneration have identified cells with multi-potency in the IVD. However, IVD tissue-specific progenitor cells and their niche components are not clear, although degenerated...
Article
Low back pain that is associated with disc degeneration contributes to a huge economic burden in the worldwide healthcare system. Traditional methods, such as spinal fusion, have been adopted to relieve mechanical back pain, but this is compromised by decreased spinal motion. Tissue engineering has attracted much attention, and aims to correct the...
Article
Full-text available
Background context: Recent studies have demonstrated new therapeutic strategy using transplantation of mesenchymal stem cells (MSCs), especially bone marrow-derived MSCs (BM-MSCs), to preserve intervertebral disc (IVD) structure and functions. It is important to understand whether and how the MSCs survive and thrive in the hostile microenvironment...
Article
Introduction Cadherins are transmembrane glycoproteins that mediate calcium-dependent cell adhesion. Recent studies suggest that cadherins also have nonadhesive functions. Maturation of human intervertebral disk (IVD) as well as early events of IVD degeneration in a mouse model ¹ is associated with segregation of nucleus pulposus (NP) cells suggest...
Article
Introduction Confluent fibrosis, manifested as over-accumulation of fibrous matrix during tissue repair or remodeling, leads to scar formation and often organ failure. Studies suggest that 68% of protruded intervertebral disks and 44% of prolapsed IVD exhibit signs of fibrosis in the nucleus pulposus (NP) and that disk scarring indicates advanced s...
Article
Introduction Stem cells possess great potential in treating disk degeneration. MSC is the most clinically relevant cell source but its functional outcomes are still far from satisfaction. One of the primary reasons for the suboptimal performance of MSCs is that the majority of injected cells leaked out from the injection path. Existing attempts add...
Article
Full-text available
Introduction Bovine intervertebral disc (IVD) is an attractive candidate for studying IVD degeneration due to its anatomical and mechanical loading similarity with IVD in skeletally developed human. Nucluse pulposus (NP) is the central part of IVD and important for understanding IVD degeneration. Enzymatic digestion by collagenase has been employe...
Article
Full-text available
The past decade has witnessed numerous publications on mesenchymal stem cells (MSC), which have great potential in regenerative medicine. MSC from various types of origins exhibit different characteristics, which may relate to the maintenance role of MSC in that specific source. Reports have emerged that among the most widely investigated sources,...
Article
Intervertebral disc (IVD) degeneration and its associated low back pain affects a large proportion of the worldwide population and is characterised by biochemical changes in the IVD, such as loss of proteoglycans and water, which leads to structural and functional changes of the IVD. The majority of conventional treatments for IVD degeneration aim...
Article
Full-text available
Implantation of intervertebral disc (IVD) allograft or tissue engineered disc constructs in the spine has emerged as an alternative to artificial disc replacement for the treatment of severe degenerative disc disease (DDD). Establishment of a bank of cryopreserved IVD allografts enables size matching and facilitates logistics for effective clinical...
Data
Additional gene/protein expression data and EMSA. (A) Expression of Col2a1 and Col10a1 in CCL, MCTs, and MC3T3-E1 was analyzed by RT-PCR. Controls were no RNA (−) or RNA from mouse E17.5 embryo (+). Expression of Col10a1 was found only in MCTs. (B) Western blot analysis showed that both SOX9 and RUNX2 were highly expressed in CCL but weakly in MCTs...
Data
Full-text available
Alignment data from SOX9-GLI site analysis. Multispecies alignment of regions spanning the linked SOX9-GLI sites are shown along with chromosomal location (Chr), identical nucleotides (.), insertion or deletion (-), and unaligned positions ( = ). (PDF)
Data
In vivo transcriptional activity of Col10a1 element A. (A) Expression pattern of Col10Flag-E in E15.5 transgenic fetus (mid-sagittal plane) examined by in-situ hybridization using digoxigenin-labeled probes. Flag expression was detected in the hypertrophic chondrocytes of cervical pedicle (a) and developing vertebrae (b). Weak expression was detect...
Data
Additional details of experiments. (DOC)