Accentuating the sources of mesenchymal stem cells as cellular therapy for osteoarthritis knees-a panoramic review.
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ABSTRACT:
SUBMITTER: Muthu S
PROVIDER: S-EPMC8327191 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Osteoarthritis (OA) is a painful chronic condition with a significant impact on quality of life. The societal burden imposed by OA is increasing in parallel with the aging population; however, no therapies have demonstrated efficacy in preventing the progression of this degenerative joint disease. Current mainstays of therapy include activity modification, conservative pain management strategies, weight loss, and if necessary, replacement of the affected joint. Mesenchymal stem cells (MSCs) are a multipotent endogenous population of progenitors capable of differentiation to musculoskeletal tissues. MSCs have a well-documented immunomodulatory role, managing the inflammatory response primarily through paracrine signaling. Given these properties, MSCs have been proposed as a potential regenerative cell therapy source for patients with OA. Research efforts are focused on determining the ideal source for derivation, as MSCs are native to several tissues. Furthermore, optimizing the mode of delivery remains a challenge both for appropriate localization of MSCs and for directed guidance toward stemming the local inflammatory process and initiating a regenerative response. Scaffolds and matrices with growth factor adjuvants may prove critical in this effort. The purpose of this review is to summarize the current state of MSC-based therapeutics for OA and discuss potential barriers that must be overcome for successful implementation of cell-based therapy as a routine treatment strategy in orthopedics.
| S-EPMC4559256 | biostudies-literature
Project description:Osteoarthritis (OA) is a degenerative disorder of the cartilage and is one of the leading causes of disability, particularly amongst the elderly, wherein patients with advanced-stage OA experience chronic pain and functional impairment of the limbs, thus resulting in a significantly reduced quality of life. The currently available treatments primarily revolve around symptom management, and is thus palliative rather than curative. The aim of the present review is to briefly discuss the limitations of some of the currently available treatments for patients with OA, and highlight the value of the potential use of stem cells in cellular therapy, which is widely regarded as the breakthrough that can address the present unmet medical needs for treatment of degenerative diseases, such as OA. The advantages of stem cell therapy, particularly mesenchymal stem cells, and the challenges involved are also discussed in this review.
| S-EPMC8212446 | biostudies-literature
Project description:Utilization of joint-resident mesenchymal stem cells (MSC) to repair articular cartilage is a promising strategy in osteoarthritis (OA) therapy but remains a considerable research challenge. Here, hierarchical targeting and microenvironment responsive peptide functionalized nanoparticles (NPs) are used to achieve cartilage repair in situ. Ultrasmall copper oxide (CuO) NPs are conjugated with type 2 collagen and MSC dual-targeting peptide (designated WPV) with a matrix metalloproteinase 2 (MMP-2)-sensitive sequence as a spacer to achieve hierarchical targeting. Guided by this peptide, WPV-CuO NPs initially penetrate cartilage and subsequently expose the inner MSC-targeted peptide to attract MSCs through MMP-2 clearance. CuO further promotes chondrogenesis of MSCs. In an anterior cruciate ligament transection rat model, intraarticular injection of WPV-CuO NPs induces significant reduction of cartilage destruction. The therapeutic mechanism involves inhibition of the PI3K/AKT/mTOR pathway, as determined via transcriptome analysis. In conclusion, a novel therapeutic strategy for OA has been successfully developed based on localized MSC recruitment and cartilage repair without transplantation of exogenous cells or growth factors.
| S-EPMC8858465 | biostudies-literature
Project description:Stem cells are considered to be one of the greatest potential treatments to cure degenerative diseases. Stem cells injection for knee osteoarthritis (OA) is still a relatively new treatment and has not yet gained popularity. So, the effectiveness, safety and potential of mesenchymal stem cells (MSCs) for knee OA treatment is worthy to be explored. Explore the effectiveness and safety of mesenchymal stem cells (MSCs) in the treatment of knee osteoarthritis. We collected clinical trials using MSCs as treatment for knee OA (before April 2019), including randomized controlled trials (RCTs), retrospective studies and cohort studies. We searched PubMed, EMBASE, Cochrane Library, Web of Science and the ClinicalTrials.gov with keywords (Mesenchymal stem cells [MSCs], Knee osteoarthritis, Effectiveness and Safety), and then performed a systematic review and cumulative metaanalysis of all RCTs and retrospective comparative studies. To evaluate the effectiveness and safety of MSC in knee OA treatment, we applied visual analog scale score, Western Ontario and McMaster Universities Osteo-arthritis Index and adverse events. We included 15 RCTs, two retrospective studies and two cohort studies including a total of 584 knee OA patients in this study. We demonstrated that MSC treatment could significantly decrease visual analog scale in a 12-month follow-up study compared with controls (p < 0.001). MSC therapy also showed significant decreases in Western Ontario and McMaster Universities Osteoarthritis Index scores after the 6-month follow-up (p < 0.001). MSC therapy showed no difference compared with controls (p > 0.05) in adverse events. We suggest that MSC therapy could serve as an effective and safe therapy for clinical application in OA treatment.The translational potential of this articleThis study provided the best available evidence and a wider perspective to MSCs application in the management of knee OA. MSCs therapy will have great translational potential in the clinical treatment of various degenerative diseases once optimum formula and explicit target population are identified.
| S-EPMC7452318 | biostudies-literature
Project description:Cell based therapies are increasingly used and results of bone marrow aspirate concentrate (BMAC) show encouraging short- to middle term results, superior to hyaluronic acid and platelet rich plasma (PRP). Most studies describe patients with mild to moderate arthritis and results of patients with KL III and IV osteoarthritis of the knee are limited to short term evaluations. Hence, the aim of this prospective study was to investigate the mid-term outcome of BMAC injections in patients with severe osteoarthritis of the knee. The BMAC was retrieved from the iliac crest as previously published with the "reorientation technique" from the iliac crest in supine position in analgosedation and injected into the patients' osteoarthritic knees. Patients were followed-up for 4 years. WOMAC, IKDC, SF 36 and walking distance were measured in a total of 37 participants. There was an improvement of IKDC and WOMAC from the first year onwards and a significant improvement beginning from year 2 up to the mid-term follow-up: IKDC increased significantly from 56 ± 12 (range 34-81) to 73 ± 13 (range 45-100), p < 0.001. WOMAC decreased significantly from 40 ± 23 (range 6-96) to 18 ± 18 (range 0-67), p < 0.001. 35 of 37 knees improved regarding IKDC and WOMAC score from the first to the last follow-up. Not a single protheses had to be implanted. Elaborate statistical analysis was done to exclude covariates and confounders (age, time, BMI,…). In summary, this is the first study on BMAC injections into 37 osteoarthritic knees with a 4-year follow up showing significant improvements in IKDC and WOMAC scores, and with a 95% success rate and significant improvement in walking distance.Clinical relevance Describes the 4-year outcome of BMAC injections for knees with severe osteoarthritis.
| S-EPMC10834500 | biostudies-literature
Project description:Mesenchymal stem cells (MSCs) are at the forefront of research for a wide range of diseases, including osteoarthritis (OA). Despite having attracted the attention of orthopedists, current MSC therapy techniques are limited by poor MSC implantation in tissue defects and lack of lateral tissue integration, which has restricted the efficacy of cell therapy to alleviate OA symptoms only. Here, we developed targeted MSC therapy for OA cartilage using a cell-tissue matchmaking nanoconstruct (C-TMN). C-TMN, as an MSC vehicle, consists of a central iron oxide nanoparticle armed with two types of antibodies, one directed at the MSC surface and the other against articular cartilage. We treated rat OA articular cartilage with intra-articular injections of C-TMN with and without exogenous MSCs. We observed substantial improvements in both symptomatic and radiographic OA caused by C-TMN, which was independent of exogenous MSCs. This new approach could predict a promising future for OA management.
| S-EPMC8901617 | biostudies-literature
Project description:BackgroundHuman umbilical cord blood-derived MSCs (hUCB-MSCs) have been studied in osteoarthritis (OA) and cartilage regeneration. Our previous study demonstrated that hUCB-MSCs combined with cartilage acellular matrix injection (CAM Inj.) represent potential therapeutic agents for structural improvement and anti-inflammatory effects in a rabbit model of OA.MethodsBased on a previous study, this study has evaluated the safety and efficacy of hUCB-MSCs combined with CAM Inj. in an anterior cruciate ligament transection (ACLT) with medial meniscectomy (MMx) in a goat model. In this study, 27 goats were divided into 5 groups: normal (n = 3), OA (n = 6), OA + CAM Inj. (n = 6), OA + hUCB-MSCs (n = 6), and OA + hUCB-MSCs + CAM Inj. (n = 6). Lameness and radiographic parameters were assessed 6 months after administration, and macroscopic and histological evaluations of the goat articular cartilage were performed 6 months after intervention.ResultsThe results showed significant improvement in lameness score only in the OA + hUCB-MSCs group at 5 months after treatment (*p < 0.05), whereas the K&L score showed significant improvement only in the OA + hUCB-MSCs + CAM Inj. group 6 months after intervention (*p < 0.05). In addition, the gross findings showed significance in OA + CAM Inj. and OA + hUCB-MSCs + CAM Inj. groups 6 months after treatment (*p < 0.05 and **p < 0.01).ConclusionIn conclusion, treatment with a combination of hUCB-MSCs and CAM Inj. reduced OA symptoms and induced effective cartilage tissue repair in a goat model. We suggest the combination of hUCB-MSCs and CAM Inj. as an alternative therapy for OA.
| S-EPMC8782990 | biostudies-literature
Project description:ObjectiveTo compare the transcriptome of articular cartilage from knees with meniscus tears to knees with end-stage osteoarthritis (OA).DesignArticular cartilage was collected from the non-weight bearing medial intercondylar notch of knees undergoing arthroscopic partial meniscectomy (APM; N = 10, 49.7 ± 10.8 years, 50% females) for isolated medial meniscus tears and knees undergoing total knee arthroplasty (TKA; N = 10, 66.0 ± 7.6 years, 70% females) due to end-stage OA. Ribonucleic acid (RNA) preparation was subjected to SurePrint G3 human 8 × 60K RNA microarrays to probe differentially expressed transcripts followed by computational exploration of underlying biological processes. Real-time polymerase chain reaction amplification was performed on selected transcripts to validate microarray data.ResultsWe observed that 81 transcripts were significantly differentially expressed (45 elevated, 36 repressed) between APM and TKA samples (≥ 2 fold) at a false discovery rate of ≤ 0.05. Among these, CFD, CSN1S1, TSPAN11, CSF1R and CD14 were elevated in the TKA group, while CHI3L2, HILPDA, COL3A1, COL27A1 and FGF2 were highly expressed in APM group. A few long intergenic non-coding RNAs (lincRNAs), small nuclear RNAs (snoRNAs) and antisense RNAs were also differentially expressed between the two groups. Transcripts up-regulated in TKA cartilage were enriched for protein localization and activation, chemical stimulus, immune response, and toll-like receptor signaling pathway. Transcripts up-regulated in APM cartilage were enriched for mesenchymal cell apoptosis, epithelial morphogenesis, canonical glycolysis, extracellular matrix organization, cartilage development, and glucose catabolic process.ConclusionsThis study suggests that APM and TKA cartilage express distinct sets of OA transcripts. The gene profile in cartilage from TKA knees represents an end-stage OA whereas in APM knees it is clearly earlier in the degenerative process.
| S-EPMC6536326 | biostudies-literature
Project description:Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA.
| S-EPMC3580463 | biostudies-literature
Project description:BackgroundPersistent epithelial defects (PED), associated with limbal stem cell deficiency (LSCD), require ocular surface reconstruction with a stable corneal epithelium (CE). This study investigated CE reformation using human adipose mesenchymal stem cells (ADSC), which derived epithelial progenitors via mesenchymal-epithelial transition (MET).MethodsSTEMPRO human ADSC were cultured with specific inhibitors antagonizing glycogen synthase kinase-3 and transforming growth factor-β signaling, followed by culture under a defined progenitor cell targeted-epithelial differentiation condition to generate epithelial-like cells (MET-Epi), which were characterized for cell viability, mesenchymal, and epithelial phenotypes using immunofluorescence and flow cytometry. Tissue-engineered (TE) MET-Epi cells on fibrin gel were transplanted to corneal surface of the rat LSCD model caused by alkali injury. Epithelial healing, corneal edema, and haze grading, CE formation were assessed by fluorescein staining, slit lamp bio-microscopy, anterior segment optical coherence tomography, and immunohistochemistry.ResultsCD73high/CD90high/CD105high/CD166high/CD14negative/CD31negative human ADSC underwent MET, giving viable epithelial-like progenitors expressing δNp63, CDH1 (E-cadherin), epidermal growth factor receptor, integrin-β4, and cytokeratin (CK)-5, 9. Under defined epithelial differentiation culture, these progenitors generated MET-Epi cells expressing cell junction proteins ZO1 and occludin. When transplanted onto rat corneal surface with LSCD-induced PED, TE-MET-Epi achieved more efficient epithelial healing, suppressed corneal edema, and opacities, when compared to corneas without treatment or transplanted with TE-ADSC. CE markers (CK3, 12, and CDH1) were expressed on TE-MET-Epi-transplanted corneas but not in other control groups.ConclusionHuman ADSC-derived epithelial-like cells, via MET, recovered the CE from PED associated with LSCD. ADSC can be a viable adult stem cell source for potential autologous epithelial cell-based therapy for corneal surface disorders.
| S-EPMC6942321 | biostudies-literature