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Orthopaedic Surgery Jul 2022Intervertebral disc degeneration (IDD) causes a variety of signs and symptoms, such as low back pain (LBP), intervertebral disc herniation, and spinal stenosis, which... (Review)
Review
Intervertebral disc degeneration (IDD) causes a variety of signs and symptoms, such as low back pain (LBP), intervertebral disc herniation, and spinal stenosis, which contribute to high social and economic costs. IDD results from many factors, including genetic factors, aging, mechanical injury, malnutrition, and so on. The pathological changes of IDD are mainly composed of the senescence and apoptosis of nucleus pulposus cells (NPCs), the progressive degeneration of extracellular matrix (ECM), the fibrosis of annulus fibrosus (AF), and the inflammatory response. At present, IDD can be treated by conservative treatment and surgical treatment based on patients' symptoms. However, all of these can only release the pain but cannot reverse IDD and reconstruct the mechanical function of the spine. The latest research is moving towards the field of biotherapy. Mesenchymal stem cells (MSCs) are regard as the potential therapy of IDD because of their ability to self-renew and differentiate into a variety of tissues. Moreover, the non-coding RNAs (ncRNAs) are found to regulate many vital processes in IDD. There have been many successes in the in vitro and animal studies of using biotherapy to treat IDD, but how to transform the experimental data to real therapy which can apply to humans is still a challenge. This article mainly reviews the treatment strategies and research progress of IDD and indicates that there are many problems that need to be solved if the new biotherapy is to be applied to clinical treatment of IDD. This will provide reference and guidance for clinical treatment and research direction of IDD.
Topics: Animals; Annulus Fibrosus; Intervertebral Disc; Intervertebral Disc Degeneration; Intervertebral Disc Displacement; Mesenchymal Stem Cells; Nucleus Pulposus
PubMed: 35486489
DOI: 10.1111/os.13254 -
Cells Dec 2019Meniscal injuries have posed a challenging problem for many years, especially considering that historically the meniscus was considered to be a structure with no... (Review)
Review
Meniscal injuries have posed a challenging problem for many years, especially considering that historically the meniscus was considered to be a structure with no important role in the knee joint. This led to earlier treatments aiming at the removal of the entire structure in a procedure known as a meniscectomy. However, with the current understanding of the function and roles of the meniscus, meniscectomy has been identified to accelerate joint degradation significantly and is no longer a preferred treatment option in meniscal tears. Current therapies are now focused to regenerate, repair, or replace the injured meniscus to restore its native function. Repairs have improved in technique and materials over time, with various implant devices being utilized and developed. More recently, strategies have applied stem cells, tissue engineering, and their combination to potentiate healing to achieve superior quality repair tissue and retard the joint degeneration associated with an injured or inadequately functioning meniscus. Accordingly, the purpose of this current review is to summarize the current available pre-clinical and clinical literature using stem cells and tissue engineering for meniscal repair and regeneration.
Topics: Biomechanical Phenomena; Humans; Knee Joint; Meniscus; Regeneration; Stem Cell Transplantation; Stem Cells; Tibial Meniscus Injuries
PubMed: 31905968
DOI: 10.3390/cells9010092 -
Biomaterials Oct 2011Extensive scientific investigations in recent decades have established the anatomical, biomechanical, and functional importance that the meniscus holds within the knee... (Review)
Review
Extensive scientific investigations in recent decades have established the anatomical, biomechanical, and functional importance that the meniscus holds within the knee joint. As a vital part of the joint, it acts to prevent the deterioration and degeneration of articular cartilage, and the onset and development of osteoarthritis. For this reason, research into meniscus repair has been the recipient of particular interest from the orthopedic and bioengineering communities. Current repair techniques are only effective in treating lesions located in the peripheral vascularized region of the meniscus. Healing lesions found in the inner avascular region, which functions under a highly demanding mechanical environment, is considered to be a significant challenge. An adequate treatment approach has yet to be established, though many attempts have been undertaken. The current primary method for treatment is partial meniscectomy, which commonly results in the progressive development of osteoarthritis. This drawback has shifted research interest toward the fields of biomaterials and bioengineering, where it is hoped that meniscal deterioration can be tackled with the help of tissue engineering. So far, different approaches and strategies have contributed to the in vitro generation of meniscus constructs, which are capable of restoring meniscal lesions to some extent, both functionally as well as anatomically. The selection of the appropriate cell source (autologous, allogeneic, or xenogeneic cells, or stem cells) is undoubtedly regarded as key to successful meniscal tissue engineering. Furthermore, a large variation of scaffolds for tissue engineering have been proposed and produced in experimental and clinical studies, although a few problems with these (e.g., byproducts of degradation, stress shielding) have shifted research interest toward new strategies (e.g., scaffoldless approaches, self-assembly). A large number of different chemical (e.g., TGF-β1, C-ABC) and mechanical stimuli (e.g., direct compression, hydrostatic pressure) have also been investigated, both in terms of encouraging functional tissue formation, as well as in differentiating stem cells. Even though the problems accompanying meniscus tissue engineering research are considerable, we are undoubtedly in the dawn of a new era, whereby recent advances in biology, engineering, and medicine are leading to the successful treatment of meniscal lesions.
Topics: Animals; Biomechanical Phenomena; Humans; Menisci, Tibial; Regeneration; Tissue Engineering; Tissue Scaffolds
PubMed: 21764438
DOI: 10.1016/j.biomaterials.2011.06.037 -
Orthopaedics & Traumatology, Surgery &... Feb 2015The glenoid labrum is the fibrocartilage of the shoulder joint, anchoring the joint capsule and shoulder ligaments. Morphology varies regionally, especially in the... (Review)
Review
The glenoid labrum is the fibrocartilage of the shoulder joint, anchoring the joint capsule and shoulder ligaments. Morphology varies regionally, especially in the superior and anterior region; these variants can sometimes be confused with pathological aspects. The labrum is often involved in shoulder pathology, by single trauma or, more often, repeated microtrauma. It seems logical to classify and to describe tears according to two criteria: the sector involved, and associated pain or instability. In the superior labrum, SLAP lesions are the most frequent. These combine labral lesion and lesion of the proximal insertion of the long head of the biceps brachii tendon. The most frequent form is SLAP II. They may be associated with instability or not. In the antero-inferior and postero-inferior labrum, lesions are mainly due to instability, particularly Bankart lesions (capsulolabral avulsion) anteriorly and Kim's lesion posteriorly. Circumferential labral lesions may be found in unstable shoulder. Finally, postero-superior lesions involve Walch's internal impingement: repeated contact between the deep surface of the cuff and the labrum, which takes on a degenerative aspect, with a kissing lesion of the cuff. There is no general rule for management: some labral lesions are resected and others fixed. The cause (which is usually shoulder instability), however, needs to be assessed and treated.
Topics: Arthroscopy; Biomechanical Phenomena; Diagnostic Imaging; Fibrocartilage; Glenoid Cavity; Humans; Joint Instability; Physical Examination; Shoulder Injuries; Shoulder Joint
PubMed: 25596985
DOI: 10.1016/j.otsr.2014.06.028 -
Advanced Drug Delivery Reviews Jun 2019Once damaged, articular cartilage has a limited potential to repair. Clinically, a repair tissue is formed, yet, it is often mechanically inferior fibrocartilage. The... (Review)
Review
Once damaged, articular cartilage has a limited potential to repair. Clinically, a repair tissue is formed, yet, it is often mechanically inferior fibrocartilage. The use of monolayer expanded versus naïve cells may explain one of the biggest discrepancies in mesenchymal stromal/stem cell (MSC) based cartilage regeneration. Namely, studies utilizing monolayer expanded MSCs, as indicated by numerous in vitro studies, report as a main limitation the induction of type X collagen and hypertrophy, a phenotype associated with endochondral bone formation. However, marrow stimulation and transfer studies report a mechanically inferior collagen I/II fibrocartilage as the main outcome. Therefore, this review will highlight the collagen species produced during the different therapeutic approaches. New developments in scaffold design and delivery of therapeutic molecules will be described. Potential future directions towards clinical translation will be discussed. New delivery mechanisms are being developed and they offer new hope in targeted therapeutic delivery.
Topics: Animals; Fibrocartilage; Humans; Hyaline Cartilage
PubMed: 30605736
DOI: 10.1016/j.addr.2018.12.015 -
Biomaterials Jun 2017The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to... (Review)
Review
The intervertebral disc contributes to motion, weight bearing, and flexibility of the spine, but is susceptible to damage and morphological changes that contribute to pathology with age and injury. Engineering strategies that rely upon synthetic materials or composite implants that do not interface with the biological components of the disc have not met with widespread use or desirable outcomes in the treatment of intervertebral disc pathology. Here we review bioengineering advances to treat disc disorders, using cell-supplemented materials, or acellular, biologically based materials, that provide opportunity for cell-material interactions and remodeling in the treatment of intervertebral disc disorders. While a field still in early development, bioengineering-based strategies employing novel biomaterials are emerging as promising alternatives for clinical treatment of intervertebral disc disorders.
Topics: Animals; Biocompatible Materials; Humans; Intervertebral Disc; Regeneration; Tissue Engineering; Wound Healing
PubMed: 28324865
DOI: 10.1016/j.biomaterials.2017.03.013 -
International Journal of Molecular... Jun 2022Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging,... (Review)
Review
Intervertebral disc degeneration (IVDD) is a common cause of lower back pain (LBP), which burdens individuals and society as a whole. IVDD occurs as a result of aging, mechanical trauma, lifestyle factors, and certain genetic abnormalities, leads to loss of nucleus pulposus, alteration in the composition of the extracellular matrix, excessive oxidative stress, and inflammation in the intervertebral disc. Pharmacological and surgical interventions are considered a boon for the treatment of IVDD, but the effectiveness of those strategies is limited. Mesenchymal stem cells (MSCs) have recently emerged as a possible promising regenerative therapy for IVDD due to their paracrine effect, restoration of the degenerated cells, and capacity for differentiation into disc cells. Recent investigations have shown that the pleiotropic effect of MSCs is not related to differentiation capacity but is mediated by the secretion of soluble paracrine factors. Early studies have demonstrated that MSC-derived exosomes have therapeutic potential for treating IVDD by promoting cell proliferation, tissue regeneration, modulation of the inflammatory response, and reduced apoptosis. This paper highlights the current state of MSC-derived exosomes in the field of treatment of IVDD with further possible future developments, applications, and challenges.
Topics: Exosomes; Humans; Intervertebral Disc; Intervertebral Disc Degeneration; Mesenchymal Stem Cells; Nucleus Pulposus
PubMed: 35806304
DOI: 10.3390/ijms23137306 -
Theranostics 2021Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current... (Review)
Review
Low back pain (LBP) is a major reason for disability, and symptomatic intervertebral disc (IVD) degeneration (IDD) contributes to roughly 40% of all LBP cases. Current treatment modalities for IDD include conservative and surgical strategies. Unfortunately, there is a significant number of patients in which conventional therapies fail with the result that these patients remain suffering from chronic pain and disability. Furthermore, none of the current therapies successfully address the underlying biological problem - the symptomatic degenerated disc. Both spinal fusion as well as total disc replacement devices reduce spinal motion and are associated with adjacent segment disease. Thus, there is an unmet need for novel and stage-adjusted therapies to combat IDD. Several new treatment options aiming to regenerate the IVD are currently under investigation. The most common approaches include tissue engineering, growth factor therapy, gene therapy, and cell-based treatments according to the stage of degeneration. Recently, the regenerative activity of small molecules (low molecular weight organic compounds with less than 900 daltons) on IDD was demonstrated. However, small molecule-based therapy in IDD is still in its infancy due to limited knowledge about the mechanisms that control different cell signaling pathways of IVD homeostasis. Small molecules can act as anti-inflammatory, anti-apoptotic, anti-oxidative, and anabolic agents, which can prevent further degeneration of disc cells and enhance their regeneration. This review pursues to give a comprehensive overview of small molecules, focusing on low molecular weight organic compounds, and their potential utilization in patients with IDD based on recent , and pre-clinical studies.
Topics: Animals; Apoptosis; Humans; Inflammation; Intervertebral Disc; Intervertebral Disc Degeneration; Oxidative Stress; Regeneration
PubMed: 33391459
DOI: 10.7150/thno.48987 -
Cell and Tissue Research Oct 2017The degradation of cartilage in the human body is impacted by aging, disease, genetic predisposition and continued insults resulting from daily activity. The burden of... (Review)
Review
The degradation of cartilage in the human body is impacted by aging, disease, genetic predisposition and continued insults resulting from daily activity. The burden of cartilage defects (osteoarthritis, rheumatoid arthritis, intervertebral disc damage, knee replacement surgeries, etc.) is daunting in light of substantial economic and social stresses. This review strives to broaden the scope of regenerative medicine and tissue engineering approaches used for cartilage repair by comparing and contrasting the anatomical and functional nature of the meniscus, articular cartilage (AC) and nucleus pulposus (NP). Many review papers have provided detailed evaluations of these cartilages and cartilage-like tissues individually but none have comprehensively examined the parallels and inconsistencies in signaling, genetic expression and extracellular matrix composition between tissues. For the first time, this review outlines the importance of understanding these three tissues as unique entities, providing a comparative analysis of anatomy, ultrastructure, biochemistry and function for each tissue. This novel approach highlights the similarities and differences between tissues, progressing research toward an understanding of what defines each tissue as distinctive. The goal of this paper is to provide researchers with the fundamental knowledge to correctly engineer the meniscus, AC and NP without inadvertently developing the wrong tissue function or biochemistry.
Topics: Animals; Biomechanical Phenomena; Cartilage, Articular; Collagen; Humans; Meniscus; Nucleus Pulposus; Regeneration; Tissue Engineering
PubMed: 28413859
DOI: 10.1007/s00441-017-2613-0 -
Advanced Science (Weinheim,... May 2022Intervertebral disc degeneration (IDD) results from the dysfunction of nucleus pulposus (NP) cells and the exhaustion of NP progenitors (ProNPs). The cellular...
Intervertebral disc degeneration (IDD) results from the dysfunction of nucleus pulposus (NP) cells and the exhaustion of NP progenitors (ProNPs). The cellular applications of NP cells during IDD are currently limited due to the lack of in vivo studies showing whether NP cells are heterogeneous and contain ProNPs throughout postnatal stages. In this study, single-cell RNA sequencing of purified NP cells is used to map four molecularly defined populations and urotensin II receptor (UTS2R)-expressing postnatal ProNPs is identified, which are markedly exhausted during IDD, in mouse and human specimens. The lineage tracing shows that UTS2R ProNPs preferentially resides in the NP periphery with its niche factor tenascin-C and give rise to functional NP cells. It is also demonstrated that transplanting UTS2R ProNPs with tenascin-C into injured intervertebral discs attenuate the progression of IDD. The study provides a novel NP cell atlas, identified resident ProNPs with regenerative potential, and revealed promising diagnostic and therapeutic targets for IDD.
Topics: Animals; Homeostasis; Intervertebral Disc; Intervertebral Disc Degeneration; Mice; Nucleus Pulposus; Tenascin
PubMed: 35195356
DOI: 10.1002/advs.202104888