Disc Regeneration Research Articles

Ion elemental-optimized layered double hydroxide nanoparticles promote chondrogenic differentiation and intervertebral disc regeneration of mesenchymal stem cells through focal adhesion signaling pathway.

Chronic low back pain and dyskinesia caused by intervertebral disc degeneration (IDD) are seriously aggravated and become more prevalent with age. Current clinical treatments do not restore the biological structure and inherent function of the disc. The emergence of tissue engineering and regenerative medicine has provided new insights into the treatment of IDD. We synthesized biocompatible layered double hydroxide (LDH) nanoparticles and optimized their ion elemental compositions to promote chondrogenic differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). The chondrogenic differentiation of LDH-treated MSCs was validated using Alcian blue staining, qPCR, and immunofluorescence analyses. LDH-pretreated hUC-MSCs were differentiated prior to transplantation into the degenerative site of a needle puncture IDD rat model. Repair and regeneration evaluated using X-ray, magnetic resonance imaging, and tissue immunostaining 4–12 weeks after transplantation showed recovery of the disc space height and integrated tissue structure. Transcriptome sequencing revealed significant regulatory roles of the extracellular matrix (ECM) and integrin receptors of focal adhesion signaling pathway in enhancing chondrogenic differentiation and thus prompting tissue regeneration. The construction of ion-specific LDH nanomaterials for in situ intervertebral disc regeneration through the focal adhesion signaling pathway provides theoretical basis for clinical transformation in IDD treatment.

Vasorin-containing small extracellular vesicles retard intervertebral disc degeneration utilizing an injectable thermoresponsive delivery system

Intervertebral disc degeneration (IDD) is the pathological reason of back pain and the therapeutic approaches are still unsatisfactory. Recently, mesenchymal stem cell-derived small extracellular vesicles (EVs) have emerged as the novel regenerative method for IDD. In this study, we intensively investigated the therapeutic mechanism of small EVs, and found that vasorin protein enriched in EVs promoted the proliferation and extracellular matrix anabolism of nucleus pulposus cells via the Notch1 signaling pathway. Then, we fabricated a thermoresponsive gel which composed of Pluronic F127 and decellularized extracellular matrix (FEC) for the delivery and sustained release of EVs. Besides, ex vivo and in vivo results showed that EVs embedded in FEC (EVs@FEC) ameliorate the disc degeneration efficiently and achieve better therapeutic effects than one-off EVs delivery. Collectively, these findings deepen the understanding of EVs mechanism in treating intervertebral disc degeneration, and also illustrate the promising capacity of sustained EVs release system for intervertebral disc regeneration.

Exosomes and exosomal miRNAs: A new therapy for intervertebral disc degeneration.

Low back pain has been found as a major cause of global disease burden and disability. Intervertebral disc degeneration is recognized as the vital factor causing low back pain. Intervertebral disc degeneration has a complex mechanism and cannot be avoided. Traditional strategies for the treatment of intervertebral disc degeneration cannot meet the needs of intervertebral disc regeneration, so novel treatment methods are urgently required. Exosomes refer to extracellular vesicles that can be released by most cells, and play major roles in intercellular material transport and information transmission. MicroRNAs have been identified as essential components in exosomes, which can be selectively ingested by exosomes and delivered to receptor cells for the regulation of the physiological activities and functions of receptor cells. Existing studies have progressively focused on the role of exosomes and exosomal microRNAs in the treatment of intervertebral disc degeneration. The focus on this paper is placed on the changes of microenvironment during intervertebral disc degeneration and the biogenesis and mechanism of action of exosomes and exosomal microRNAs. The research results and deficiencies of exosomes and exosomal microRNAs in the regulation of apoptosis, extracellular matrix homeostasis, inflammatory response, oxidative stress, and angiogenesis in intervertebral disc degeneration are primarily investigated. The aim of this paper is to identify the latest research results, potential applications and challenges of this emerging treatment strategy.

Regenerative Medicine: Pharmacological Considerations and Clinical Role in Pain Management.

Purpose of ReviewLow back pain affects at least 80% of individuals at some point in their lifetime and is the fifth most common reason for physician visits in the USA. Treatment of an acute episode of LBP generally includes rest, activity modification, physical therapy, NSAIDs, and patient education.Recent FindingsA small percentage of patients will develop chronic pain lasting > 6 months duration. Platelet-rich plasma (PRP) is one of the main pillars of regenerative medicine, as its release of bioactive proteins supports the aim of RM of restoring the anatomical function in degenerative conditions. Mesenchymal stem cells (MSCs) are multipotent stem cells, multipotent progenitor cells, or marrow stromal cells found in various body tissues, including bone marrow, lung, and adipose tissue. Evidence from well-designed case–control or cohort studies for the use of PRP and MSCs in lumbar facet joint, lumbar epidural, and sacroiliac joint injections is currently described as level IV evidence. PRP and MSCs are used autogenously to help facilitate the healing process, and their injection has been studied in the long-term management of discogenic low back pain. PRP has been compared to steroid injections in the sacroiliac joint for chronic low back pain, with favorable results. MSCs have also been shown to be useful in intervertebral disc regeneration and treatment of chronic low back pain associated with degenerative disc disease.SummaryCurrently, the price for these treatments is extremely high, and thus the standard of care continues to be steroid injections and other treatments. This could change, however, with more robust data and research on the safety and long-term efficacy of biologics compared to other interventional management.

Detergent-Free Decellularization of Notochordal Cell-Derived Matrix Yields a Regenerative, Injectable, and Swellable Biomaterial

Porcine notochordal cell-derived matrix (NCM) has anti-inflammatory and regenerative effects on degenerated intervertebral discs. For its clinical use, safety must be assured. The porcine DNA is concerning because of (1) the transmission of endogenous retroviruses and (2) the inflammatory potential of cell-free DNA. Here, we present a simple, detergent-free protocol: tissue lyophilization lyses cells, and matrix integrity is preserved by limiting swelling during decellularization. DNA is digested quickly by a high nuclease concentration, followed by a short washout. Ninety-four percent of DNA was removed, and there was no loss of glycosaminoglycans or collagen. Forty-three percent of the total proteins remained in the decellularized NCM (dNCM). dNCM stimulated as much GAG production as NCM in nucleus pulposus cells but lost some anti-inflammatory effects. Reconstituted pulverized dNCM yielded a soft, shear-thinning biomaterial with a swelling ratio of 350% that also acted as an injectable cell carrier (cell viability >70%). dNCM can therefore be used as the basis for future biomaterials aimed at disc regeneration on a biological level and may restore joint mechanics by creating swelling pressure within the intervertebral disc.

The role of microenvironment in stem cell-based regeneration of intervertebral disc.

Regenerative medicine for intervertebral disc (IVD) disease, by utilizing chondrocytes, IVD cells, and stem cells, has progressed to clinical trials in the treatment of back pain, and has been studied in various animal models of disc degeneration in the past decade. Stem cells exist in their natural microenvironment, which provides vital dynamic physical and chemical signals for their survival, proliferation and function. Long-term survival, function and fate of mesenchymal stem cells (MSCs) depend on the microenvironment in which they are transplanted. However, the transplanted MSCs and the endogenous disc cells were influenced by the complicated microenvironment in the degenerating disc with the changes of biochemical and biophysical components. It is important to understand how the MSCs and endogenous disc cells survive and thrive in the harsh microenvironment of the degenerative disc. Furthermore, materials containing stem cells and their natural microenvironment have good clinical effects. However, the implantation of tissue engineering IVD (TE-IVD) cannot provide a complete and dynamic microenvironment for MSCs. IVD graft substitutes may need further improvement to provide the best engineered MSC microenvironment. Additionally, the IVD progenitor cells inside the stem cell niches have been regarded as popular graft cells for IVD regeneration. However, it is still unclear whether actual IVD progenitor cells exist in degenerative spinal conditions. Therefore, the purpose of this review is fourfold: to discuss the presence of endogenous stem cells; to review and summarize the effects of the microenvironment in biological characteristics of MSC, especially those from IVD; to explore the feasibility and prospects of IVD graft substitutes and to elaborate state of the art in the use of MSC transplantation for IVD degeneration in vivo as well as their clinical application.

Advances in Tissue Engineering of the Temporomandibular Joint Disc: An Overview of Current Status and Future Directions.

Advances in tissue engineering have progressed to potentially offer a solution to temporomandibular joint disc (TMJ) disorders not amenable to conservative therapies. Conclusive treatment options for patients with end-stage disc disorders requires discectomy and reconstruction of the articular disc with various materials. Tissue engineering TMJ disc is a promising alternative to the limited and sometimes inadequate clinical options in the management of such disorders. However, tissue engineering is far from completion for the TMJ disc regeneration. This review briefly discusses the properties of native disc, the mechanism by which TMJ disorders manifest, and how a tissue engineered disc could assuage the problems inherent in the management of such disorders. Furthermore, the review addresses and provides updates to relevant themes of tissue engineering in regards to the TMJ disc, namely, the scaffolds, cells and biomarkers, hurdles in tissue engineering of the disc, and its application in translation to the clinical practice and future directions.

Mesenchymal Stem Cell-Derived Exosomes and Intervertebral Disc Regeneration: 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.

Importance of Matrix Cues on Intervertebral Disc Development, Degeneration, and Regeneration.

Back pain is one of the leading causes of disability worldwide and is frequently caused by degeneration of the intervertebral discs. The discs’ development, homeostasis, and degeneration are driven by a complex series of biochemical and physical extracellular matrix cues produced by and transmitted to native cells. Thus, understanding the roles of different cues is essential for designing effective cellular and regenerative therapies. Omics technologies have helped identify many new matrix cues; however, comparatively few matrix molecules have thus far been incorporated into tissue engineered models. These include collagen type I and type II, laminins, glycosaminoglycans, and their biomimetic analogues. Modern biofabrication techniques, such as 3D bioprinting, are also enabling the spatial patterning of matrix molecules and growth factors to direct regional effects. These techniques should now be applied to biochemically, physically, and structurally relevant disc models incorporating disc and stem cells to investigate the drivers of healthy cell phenotype and differentiation. Such research will inform the development of efficacious regenerative therapies and improved clinical outcomes.

Fucoidan-loaded nanofibrous scaffolds promote annulus fibrosus repair by ameliorating the inflammatory and oxidative microenvironments in degenerative intervertebral discs

Tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD). However, implantation of tissue engineered constructs may cause foreign body reaction and aggravate the inflammatory and oxidative microenvironment of the degenerative intervertebral disc (IVD). In order to ameliorate the adverse microenvironment of IDD, in this study, we prepared a biocompatible poly (ether carbonate urethane) urea (PECUU) nanofibrous scaffold loaded with fucoidan, a natural marine bioactive polysaccharide which has great anti-inflammatory and antioxidative functions. Compared with pure PECUU scaffold, the fucoidan-loaded PECUU nanofibrous scaffold (F-PECUU) decreased the gene and protein expression related to inflammation and the oxidative stress in the lipopolysaccharide (LPS) induced annulus fibrosus cells (AFCs) significantly (p<0.05). Especially, gene expression of Il 6 and Ptgs2 was decreased more than 50% in F-PECUU with 3.0 wt% fucoidan (HF-PECUU). Moreover, the gene and protein expression related to the degradation of extracellular matrix (ECM) were reduced in a fucoidan concentration-dependent manner significantly, with increased almost 3 times gene expression of Col1a1 and Acan in HF-PECUU. Further, in a ‘box’ defect model, HF-PECUU decreased the expression of COX-2 and deposited more ECM between scaffold layers when compared with pure PECUU. The disc height and nucleus pulposus hydration of repaired IVD reached up to 75% and 85% of those in the sham group. In addition, F-PECUU helped to maintain an integrate tissue structure with a similar compression modulus to that in sham group. Taken together, the F-PECUU nanofibrous scaffolds showed promising potential to promote AF repair in IDD treatment by ameliorating the harsh degenerative microenvironment. Statement of SignificanceAnnulus fibrosus (AF) tissue engineering holds potential in the treatment of intervertebral disc degeneration (IDD), but is restricted by the inflammatory and oxidative microenvironment of degenerative disc. This study developed a biocompatible polyurethane scaffold (F-PECUU) loaded with fucoidan, a marine bioactive polysaccharide, for ameliorating IDD microenvironment and promoting disc regeneration. F-PECUU alleviated the inflammation and oxidative stress caused by lipopolysaccharide and prevented extracellular matrix (ECM) degradation in AF cells. In vivo, it promoted ECM deposition to maintain the height, water content and mechanical property of disc. This work has shown the potential of marine polysaccharides-containing functional scaffolds in IDD treatment by ameliorating the harsh microenvironment accompanied with disc degeneration.

Regenerating and repairing degenerative intervertebral discs by regulating the micro/nano environment of degenerative bony endplates based on low-tension mechanics

BackgroundConservative treatment is the recommended first-line treatment for degenerative disc diseases. Traction therapy has historically been one of the most common clinical methods to address this, but the clinical effect remains controversial.MethodsForty-two six-month-old male Sprague-Dawley rats were randomly divided into six groups: the model group (Group A, four coccyx vertebrae (Co7-Co10) were fixed with customized external fixators, and the vertebral disc degeneration model was constructed by axial compression of the target segment Co8 - Co9 for 4 weeks), the experimental control group (Group B, after successful modeling, the external fixation device was removed and self-rehabilitation was performed) and four intervention groups (Groups C to F): Groups C and E: Co8 - Co9 vertebrae compressed for 4 weeks followed by two or 4 weeks of high tension traction (HTT), respectively, and Groups D and F: vertebrae compressed for 4 weeks followed by two or 4 weeks of low-tension traction (LTT), respectively. Imaging tests (X-ray and MRI) were performed to assess disc height and T2 signal intensity at each time point. After the experiment, the animals were euthanized, and the caudal vertebrae were collected for analysis of intervertebral disc histopathology, proteoglycan content, and micronanostructure of the annulus fibrosus, nucleus pulposus and bony endplate.ResultsSigns of tissue regeneration were apparent in all four intervention groups. After two to 4 weeks of intervention (HTT and LTT), the morphology of pores in the bony endplate, their number, and diameter had recovered significantly compared with those in Group A. The LTT group was superior to the HTT group, and the 4w in situ group was significantly superior to the 2w group. Meanwhile, the histological scores of discs, the mean fibril diameter and modulus of annulus fibrosus were significantly improved compared with the control groups, and the LTT group was superior to HTT group.ConclusionsLow-tension traction better promotes active reconstruction of bony endplates and improves the elastic modulus and micro/nanostructure of the disc. Thus, it further promotes the regeneration and repair of intervertebral discs.

Is there a chance for regeneration of intervertebral discs? A preliminary study

Introduction: Segmental instability of the spine caused by the decreased height of intervertebral discs is one of the major causes of chronic low back pain affecting 70-80% of the adult population. The decrease in height is due to degenerative lesions induced by vertical compression overload of the disc. Objective: A preliminary study was performed to determine if disc degeneration due to overload could be stopped. We hypothesized that disc distraction during fission surgery from posterior approach could reduce the pressure on the discs, degeneration could be stopped, and perhaps the function could be restored. Methods: To characterize the condition of the discus, we used the determination glycosaminoglycan content, which is responsible for the disc-bound water content and thus for ensuring its elasticity. The use of gadolinium contrast agent in MRI (dGEMRIC) is an accepted method for determining the glycosaminoglycan content of the intervertebral disc, as the concentration of absorbed contrast agent is inversely proportional to the number of glycosaminoglycans in the intervertebral discs. In addition to pre- and postoperative dGEMRIC data, we examined disc height, lumbar lordosis, visual analog pain scale, and the Oswestry Disability Index. Results: All patients underwent monosegmental fusion Mowing posterior distraction of the affected segment due to segmental instability. During the surgeries, lumbar lordosis did not decrease despite posterior distraction. The heights of the discus increased by an average of 3 mm, the pain decreased, and the Oswestry Disability Index improved. In the dGEMRIC studies, an average of 309.18 units/cm(2) of gadolinium accumulated in the discs before surgery, which decreased postoperatively to 174.43 units/cm(2). All changes were significant at the p = 0.05 significance level. Conclusion: The trend of our preliminary results suggests that increasing the height of the discs can reduce the hydrostatic pressure in the discs, resulting in an increase in the amount of glycosaminoglycans, which can stop the degeneration of the discs and also initiate regeneration processes.

Spinal intervertebral disc regeneration versus repair: cost, outcomesand future considerations.

Regenerative MedicineVol. 17, No. 6 CommentarySpinal intervertebral disc regeneration versus repair: cost, outcomes and future considerationsRyan Jarrah, Taylor Reardon, Tyler Warner, Frank De Stefano & Brian FianiRyan Jarrah https://orcid.org/0000-0002-3500-3688Department of Neurosurgery, Mayo Clinic, Rochester, MN 55905, USASearch for more papers by this author, Taylor Reardon https://orcid.org/0000-0002-1179-0111Kentucky College of Osteopathic Medicine, University of Pikeville, Pikeville, KY 41501, USASearch for more papers by this author, Tyler Warner https://orcid.org/0000-0002-6460-823XSchool of Medicine, St. George’s University, West Indies, GrenadaSearch for more papers by this author, Frank De Stefano https://orcid.org/0000-0003-1709-0148College of Osteopathic Medicine, Kansas City University, Kansas City, MO 64106, USASearch for more papers by this author & Brian Fiani *Author for correspondence: Tel.: +1 212 746 5454; E-mail Address: bfiani@outlook.comhttps://orcid.org/0000-0003-1700-4633Department of Neurosurgery, Weill Cornell Medical Center/New York Presbyterian Hospital, New York, NY 10065, USASearch for more papers by this authorPublished Online:12 May 2022https://doi.org/10.2217/rme-2022-0049AboutSectionsView ArticleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInReddit View articleKeywords: artificial disccell-based therapiesdisc regenerationdisc replacementimmunomodulationmesenchymal stem cells

Three-dimensional, biomimetic electrospun scaffolds reinforced with carbon nanotubes for temporomandibular joint disc regeneration

Temporomandibular disorder (TMD) remained a huge clinical challenge, with high prevalence but limited, unstable, and only palliative therapeutic methods available. As one of the most vulnerable sites implicated in TMD, the temporomandibular joint disc (TMJD) displayed a complicated microstructure, region-specific fibrocartilaginous distribution, and poor regenerative property, which all further hindered its functional regeneration. To address the problem, with versatile and relatively simple electrospinning (ELS) technique, our study successfully fabricated a biomimetic, three-dimensional poly (ϵ-caprolactone) (PCL)/polylactide (PLA)/carbon nanotubes (CNTs) disc scaffold, whose biconcave gross anatomy and regionally anisotropic microstructure recapitulating those of the native disc. As in vitro results validated the superior mechanical, bioactive, and regenerative properties of the biomimetic scaffolds with optimal CNTs reinforcement, we further performed in vivo experiments. After verifying its biocompatibility and ectopic fibrochondrogenicity in nude mice subcutaneous implantation models, the scaffolds guided disc regeneration and subchondral bone protection were also confirmed orthotopically in rabbits TMJD defected areas, implying the pivotal role of morphological cues in contact-guided tissue regeneration. In conclusion, our work represents a significant advancement in complex, inhomogeneous tissue engineering, providing promising clinical solutions to intractable TMD ailments. Statement of significanceComplex tissue regeneration remains a huge scientific and clinical challenge. Although frequently implicated in temporomandibular joint disorder (TMD), functional regeneration of injured temporomandibular joint disc (TMJD) is extremely hard to achieve, mainly because of the complex anatomy and microstructure with regionally variant, anisotropic fiber alignments in the native disc. In this study, we developed the biomimetic electrospun scaffold with optimal CNTs reinforcement and regionally anisotropic fiber orientations. The excellent mechanical and bioactive properties were confirmed both in vitro and in vivo, effectively promoting defected discs regeneration in rabbits. Besides demonstrating the crucial role of morphological biomimicry in tissue engineering, our work also presents a feasible clinical solution for complex tissue regeneration.

Decellularized extracellular matrix-based scaffold and hypoxic priming: A promising combination to improve the phenotype of degenerate intervertebral disc cells

AimsThe main cause of low back pain is the intervertebral disc (IVD) degeneration. Designing an effective disc regeneration strategy still remains a major challenge, especially for the lack of effective self-healing capacity. Understanding the properties of IVD cells in the degenerate microenvironment could help to develop in situ regeneration strategies. The objective of the present study was to investigate the ability of degenerate cells to respond to conditions they experience physiologically in their niche in vivo, namely the presence of the hypoxic environment and trophic factors. Main methodsDegenerate cells from IVD of patients operated for herniated disc were exposed to hypoxic priming and decellularized Wharton's jelly matrix (DWJM) as scaffold and trophic factors source for 48 h in culture. Cell response was evaluated in terms of cell viability, proliferation, cytoskeletal organization, migratory ability and expression of discogenic transcription factors (SOX9, TRPS1), hypoxia-inducible factor 1α (HIF-1α) and longevity transcription factor FOXO3a. The recruitment of HIF-1α at FOXO3a and SOX9 gene promoters was analyzed by Chromatin immunoprecipitation. Key findingsDegenerate IVD cells were able to re-acquire the discogenic phenotype, and to re-adapt to hypoxia after exposure to hypoxic priming and DWJM. We demonstrated for the first time that HIF-1α is specifically recruited at the promoter of SOX9 and FOXO3a which are crucial for IVD homeostasis and repair. SignificanceThese results open new avenues to engineer IVD by demonstrating that appropriate stimuli are able to dampen the degenerated IVD cell phenotype and to promote anabolic activity in cells which are constitutively characterized by poor reparative capacity.

Intervertebral Disc Degeneration: Biomaterials and Tissue Engineering Strategies toward Precision Medicine.

Intervertebral disc degeneration is a common cause of discogenic low back pain resulting in significant disability. Current conservative or surgical intervention treatments do not reverse the underlying disc degeneration or regenerate the disc. Biomaterial-based tissue engineering strategies exhibit the potential to regenerate the disc due to their capacity to modulate local tissue responses, maintain the disc phenotype, attain biochemical homeostasis, promote anatomical tissue repair, and provide functional mechanical support. Despite preliminary positive results in preclinical models, these approaches have limited success in clinical trials as they fail to address discogenic pain. This review gives insights into the understanding of intervertebral disc pathology, the emerging concept of precision medicine, and the rationale of personalized biomaterial-based tissue engineering tailored to the severity of the disease targeting early, mild, or severe degeneration, thereby enhancing the efficacy of the treatment for disc regeneration and ultimately to alleviate discogenic pain. Further research is required to assess the relationship between disc degeneration and lower back pain for developing future clinically relevant therapeutic interventions targeted towards the subgroup of degenerative disc disease patients.

ISSLS Prize in Bioengineering Science 2022: low rate cyclic loading as a therapeutic strategy for intervertebral disc regeneration.

The intervertebral disc degenerates with age and has a poor propensity for regeneration. Small molecule transport plays a key role in long-term degradation and repair. Convection (bulk flow), induced by low rate cyclic loading of the intervertebral disc, has been shown to increase transport of small molecules. However, the potential therapeutic benefit of low rate cyclic loading on degenerated discs has not been described. The purpose of this study was to determine if a sustained (daily) low rate cyclic loading regimen could slow, arrest, or reverse intervertebral disc degeneration in the rabbit lumbar spine. Fifty-six New Zealand white rabbits (>12 months old) were designated as either Control (no disc puncture), 8D (disc puncture followed by 8 weeks of degeneration), 16D (disc puncture followed by 16 weeks of degeneration), or Therapy (disc puncture followed by 8 weeks of degeneration and then 8 weeks of daily low rate cyclic loading). Specimens were evaluated by T2 mapping, Pfirrmann scale grading, nucleus volume, disc height index, disc morphology and structure, and proteoglycan content. In every metric, mean values for the Therapy group fell between Controls and 8D animals. These results suggest that sustained low rate cyclic loading had a therapeutic effect on the already degenerated disc and the regimen promoted signs of regeneration. If these results translate clinically, this approach could fulfil a significant clinical need by providing a means of non-invasively treating intervertebral disc degeneration.

Intradiscal Injection of Autologous Discogenic Cells in Patients with Discectomy: A Prospective Clinical Study of Its Safety and Feasibility.

The treatment of intervertebral disc degeneration (IVDD) is still a huge challenge for clinical updated surgical techniques and basic strategies of intervertebral disc regeneration. Few studies have ever tried to combine surgery and cell therapy to bridge the gap between clinical and basic research. A prospective clinical study with a 72-month follow-up was conducted to assess the safety and feasibility of autologous discogenic cells transplantation combined with discectomy in the treatment of lumbar disc herniation (LDH) and to evaluate the regenerative ability of discogenic cells in IVDD. Forty patients with LDH who were scheduled to have discectomy enrolled in our study and were divided into the observed group (transplantation of autologous discogenic cells after discectomy) and control group (only-discectomy). Serial MRI and X-ray were used to evaluate the degenerative extent of index discs, and clinical scores were used to determine the symptomatic improvement. No adverse events were observed in the observed group, and seven patients in the control group underwent revisions. Both groups had significant improvement of all functional scores post-operatively, with the observed group improving more considerably at 36-month and 72-month follow-up. The height and water content of discs in both groups decreased significantly since 36 months post-op with the control group decreased more obviously. Discectomy combined with autologous discogenic cells transplantation is safe and feasible in the treatment of LDH. Radiological analysis demonstrated that discogenic cells transplantation could slow down the further degeneration of index discs and decrease the complications of discectomy.

Edifying the Focal Factors Influencing Mesenchymal Stem Cells by the Microenvironment of Intervertebral Disc Degeneration in Low Back Pain.

Intervertebral disc degeneration (IVDD) is one of the main triggers of low back pain, which is most often associated with patient morbidity and high medical costs. IVDD triggers a wide range of pathologies and clinical syndromes like paresthesia, weakness of extremities, and intermittent/chronic back pain. Mesenchymal stem cells (MSCs) have demonstrated to possess immunomodulatory functions as well as the capability of differentiating into chondrocytes under appropriate microenvironment conditions, which makes them potentially epitome for intervertebral disc (IVD) regeneration. The IVD microenvironment is composed by niche of cells, and their chemical and physical milieus have been exhibited to have robust influence on MSC behavior as well as differentiation. Nevertheless, the contribution of MSCs to the IVD milieu conditions in healthy as well as degeneration situations is still a matter of debate. It is still not clear which factors, if any, are essential for effective and efficient MSC survival, proliferation, and differentiation. IVD microenvironment clues such as nucleopulpocytes, potential of hydrogen (pH), osmotic changes, glucose, hypoxia, apoptosis, pyroptosis, and hydrogels are capable of influencing the MSCs aimed for the treatment of IVDD. Therefore, clinical usage of MSCs ought to take into consideration these microenvironment clues during treatment. Alteration in these factors could function as prognostic indicators during the treatment of patients with IVDD using MSCs. Thus, standardized valves for these microenvironment clues are warranted.

Development, Pathogenesis, and Regeneration of the Intervertebral Disc: Current and Future Insights Spanning Traditional to Omics Methods.

The intervertebral disc (IVD) is the fibrocartilaginous joint located between each vertebral body that confers flexibility and weight bearing capabilities to the spine. The IVD plays an important role in absorbing shock and stress applied to the spine, which helps to protect not only the vertebral bones, but also the brain and the rest of the central nervous system. Degeneration of the IVD is correlated with back pain, which can be debilitating and severely affects quality of life. Indeed, back pain results in substantial socioeconomic losses and healthcare costs globally each year, with about 85% of the world population experiencing back pain at some point in their lifetimes. Currently, therapeutic strategies for treating IVD degeneration are limited, and as such, there is great interest in advancing treatments for back pain. Ideally, treatments for back pain would restore native structure and thereby function to the degenerated IVD. However, the complex developmental origin and tissue composition of the IVD along with the avascular nature of the mature disc makes regeneration of the IVD a uniquely challenging task. Investigators across the field of IVD research have been working to elucidate the mechanisms behind the formation of this multifaceted structure, which may identify new therapeutic targets and inform development of novel regenerative strategies. This review summarizes current knowledge base on IVD development, degeneration, and regenerative strategies taken from traditional genetic approaches and omics studies and discusses the future landscape of investigations in IVD research and advancement of clinical therapies.