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Mean MRI scores (modified Thompson classification) of targeted discs in the PRP, PRP-BMSCs, PBS and control groups at weeks 0, 1, 2 and 8. Level data of the MRI images were analyzed using a Mann-Whitney U-test. * P<0.05. Data are presented as the mean ± standard error of the mean. PBS, phosphate-buffered saline; PRP, platelet-rich plasma; BMSCs, bone marrow-derived mesenchymal stem cells; MRI, magnetic resonance imaging.
Source publication
Platelet‑rich plasma (PRP) is a promising strategy for intervertebral disc degeneration (IDD). However, the short half‑life of growth factors released from PRP cannot continuously stimulate the degenerated discs. Thus, the present study hypothesized that the combined use of PRP and bone marrow‑derived mesenchymal stem cells (BMSCs) may repair the e...
Context in source publication
Context 1
... concentration of the PRP. The platelet concentration of the prepared PRP was 776±48x10 9 /l, whereas the concen- tration in the whole blood was only 159±21x10 9 /l. The PRP prepared in the present study contained almost five times the number of platelets in the whole blood. The MRI T2-weighted signal intensity of intervertebral discs in the PRP and PBS groups decreased significantly 8 weeks following injection, whereas the targeted discs in the PRP-BMSC groups showed maintained signal intensity, which was similar to that in the control group. White arrows indicate the signal intensity area. PBS, phosphate-buffered saline; PRP, platelet-rich plasma; BMSCs, bone marrow-derived mesenchymal stem cells; MRI, magnetic resonance imaging. intensity in all groups (Fig. 3). T2 signal intensity was stable at each time point in the control group. At 2 weeks following needle puncture (week 0), the injected discs experienced mild signal loss. The treated discs of the PBS group experienced continuous T2 signal loss during the 8-week period, whereas the discs in the PRP-BMSC group showed an increase in signal intensity over time. PRP exhibited a regenerative effect on the degenerated discs at 1 and 2 weeks following treat- ment by increasing the signal intensity. However, at week 8 post-treatment, the discs of the PRP group exhibited decreased signal intensity. To determine the degenerative changes of the targeted discs, the mean MRI score of each group was presented (Fig. 4). At weeks 1 and 2, no significant differences were found in the MRI grading between the PRP and PRP-BMSC groups (P<0.05). At week 8, the PRP-BMSC group showed a significantly higher MRI grading score, compared with the PRP group (P<0.05). H&E staining assessment. In the control group, discs without any interventions exhibited a high density of ECM. At 8 weeks following the different treatments, the discs in the PRP (Fig. 5A) and PBS (Fig. 5B) groups exhibited decreased ...
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Citations
... These contrasting results again point to the synergistic nature of PRP treatment when combined with other agents. For example, Wang and colleagues' analysis of treatments for needle-punctured rabbit IVDs showed only minor structural regeneration in PRPtreated groups; however, groups treated with combined PRP and bone marrow-derived mesenchymal stem cells had far superior disc regeneration when assessed histologically and by MRI [56]. In summary, PRP is an effective orthobiologic agent that reprograms degenerating IVD cells to an anabolic, anti-inflammatory state. ...
Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies worldwide. Conventional pharmacological treatments primarily aimed at slowing the progression of degeneration have demonstrated limited long-term efficacy and often do not address the underlying causes of the disease. On the other hand, orthobiologics are regenerative agents derived from the patient's own tissue and represent a promising emerging therapy for degenerative disc disease. This review comprehensively outlines the pathophysiology of DDD, highlighting the inadequacies of existing pharmacological therapies and detailing the potential of orthobiologic approaches. It explores advanced tools such as platelet-rich plasma and mesenchymal stem cells, providing a historical overview of their development within regenerative medicine, from foundational in vitro studies to preclinical animal models. Moreover, the manuscript delves into clinical trials that assess the effectiveness of these therapies in managing DDD. While the current clinical evidence is promising, it remains insufficient for routine clinical adoption due to limitations in study designs. The review emphasizes the need for further research to optimize these therapies for consistent and effective clinical outcomes, potentially revolutionizing the management of DDD and offering renewed hope for patients.
... These contrasting results again point to the synergistic nature of PRP treatment when combined with other agents. For example, Wang and colleagues' analysis of treatments for needle-punctured rabbit IVDs showed only minor structural regeneration in PRP-treated groups, however groups treated with combined PRP and bone marrow-derived mesenchymal stem cells had far superior disc regeneration when assessed histologically and by MRI [55]. In summary, PRP is an effective orthobiologic agent that reprograms degenerating IVD cells to an anabolic, anti-inflammatory state. ...
Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies. Traditional pharmacological treatments aimed at slowing degeneration are ineffective in the long-term. Orthobiologics, regenerative agents derived from the patient’s own tissue, are a promising emerging therapy for degenerative disc disease. This review first outlines the pathophysiology of degenerative disc disease, highlighting the limitations of existing treatments and explores the orthobiologic tools for treating degenerative disc disease (platelet-rich plasma, mesenchymal stem cells). Their history in regenerative medicine is outlined, demonstrating how in vitro evidence informed preclinical animal studies on their efficacy in treating degenerative disc disease. Finally, clinical trials utilizing these treatment options are reviewed and directions for future research are outlined. Although the current clinical evidence available is limited to propagate their routine clinical usage the field holds immense potential in the management of DDD. There is room for these treatments to be optimized for effective consistent clinical outcomes in DDD.
... By surpassing the nuclear factor-kB signaling pathway, PRP injection transforms this pathological state into one that is anabolic and anti-inflammatory. [39][40][41][42][43][44] Moreover, PRP is derived from the patient's own body, and there are antimicrobial proteins in platelets that can migrate to the injury site, which makes autologous PRP injection potentially safer. ...
Objective
Low back pain is one of the main causes of disability in the world. Although regenerative medicine may represent breakthroughs in the management of low back pain, its use remains controversial. Therefore, we conducted a meta-analysis to evaluate the clinical efficacy of platelet-rich plasma (PRP) injection therapy versus different control groups for chronic low back pain during 4 weeks, 3 months, and 6 months.
Methods
Different electronic databases were searched for randomized controlled trials up to August 2023. Mean changes from baseline in pain and Oswestry Disability Index (ODI) scores at 4 weeks, 3 months, and 6 months and standard deviations of outcome were recorded.
Results
Four articles with 154 cases were finally included in this meta-analysis. After 4 weeks, corticosteroid (CS) was the optimal treatment option for chronic low back pain in terms of improvement in pain and disability index (surface under the cumulative ranking curve [SUCRA]=71.3%, SUCRA=57.8%, respectively). After 3 months, radiofrequency (RF) emerged as the best therapy in pain (SUCRA=100%) and disability index (SUCRA=98.5%), followed by PRP (SUCRA=62.3%, SUCRA=64.3%, respectively), CS (SUCRA=24.6%, SUCRA=25.9%, respectively) and lidocaine (SUCRA=13.1%, SUCRA=11.3%, respectively). At 6 months, RF was most likely to be the best treatment in pain (SUCRA=94.9%) and disability index (SUCRA=77.3%), followed by PRP (SUCRA=71.2%, SUCRA=79.6%, respectively). However, compared with the last follow-up, there was a slight downward trend in improvement pain and disability index with RF, while PRP was still an upward trend.
Conclusion
This study demonstrated better short-term improvement of chronic low back pain with CS after 4 weeks. PRP and RF improvement effects matched, but follow-up of at least 6 months showed that PRP seemed to be more advantageous in improvement in disability indices. Considering the limitations of this study, these conclusions still need to be verified by more comparative RCTs and a longer follow-up period.
... In experimental animal models of disc degeneration, PRP, combined or not with bone marrow cells, showed inhibitory effects on degeneration and significantly restored disc properties. It was also demonstrated that PRP has an anabolic effect on disc cells, promoting increased chondrocyte activity, collagen production, and proteoglycan synthesis [59,60]. Clinical studies have reported positive outcomes, safety, and superiority over placebo of intradiscal PRP treatment, including improvements in pain and muscular atrophy [61]. ...
... Epidural PRP injections have demonstrated long-term safety and effectiveness, with platelet lysate injections leading to pain reduction and functional improvement [64]. In terms of pain and disability, better results were demonstrated for PRP rich in leukocytes for patients experiencing complex low back pain due to degenerative changes when compared to pharmacological treatment using corticosteroids [60]. ...
Background:
Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain.
Methods:
We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist.
Results:
An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas.
Conclusions:
In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.
... Chronic LBP has been successfully treated using regenerative medicine, particularly when platelet-rich plasma (PRP) and mesenchymal stem cells are used [9][10][11][12][13]. PRP was first utilized in open-heart surgery in the 1970s, then 10 years later used in maxillofacial surgery to help in wound healing in reconstructive jaw surgery [14]. ...
... The patient's peripheral blood is spun to produce a high platelet concentration before being used to create PRP. PRP encourages tissue angiogenesis and the mitogenesis of healing cells [13][14][15][16][17][18] and contains seven essential proteins including platelet-derived growth factors, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor, and adhesive proteins-fibrin, fibronectin, and vitronectin, which can support three phases of tissue healing and their repair cascade (inflammation, proliferation, and remodeling) [12][13][14][15][16]18]. Despite regenerative effects, PRP also has anti-inflammatory and anti-apoptotic by strengthening chondrogenic markers (aggrecan [AGN], collagen type II [COL2], TGF-β1) and inhibiting catabolic pathways (matrix metalloproteinase [MMP]-3, cyclooxygenase-2, interleukin-1 beta (IL-1β), tumor necrosis factor-α, MMP-1, nerve growth factor) [19,20]. ...
... The patient's peripheral blood is spun to produce a high platelet concentration before being used to create PRP. PRP encourages tissue angiogenesis and the mitogenesis of healing cells [13][14][15][16][17][18] and contains seven essential proteins including platelet-derived growth factors, transforming growth factor-β (TGF-β), vascular endothelial growth factor (VEGF), epidermal growth factor, and adhesive proteins-fibrin, fibronectin, and vitronectin, which can support three phases of tissue healing and their repair cascade (inflammation, proliferation, and remodeling) [12][13][14][15][16]18]. Despite regenerative effects, PRP also has anti-inflammatory and anti-apoptotic by strengthening chondrogenic markers (aggrecan [AGN], collagen type II [COL2], TGF-β1) and inhibiting catabolic pathways (matrix metalloproteinase [MMP]-3, cyclooxygenase-2, interleukin-1 beta (IL-1β), tumor necrosis factor-α, MMP-1, nerve growth factor) [19,20]. ...
Low back pain is one of the leading causes of disability in the world. Regenerative medicine can be one of the novel treatment breakthroughs in patients with low back pain, yet its use is still debatable. We performed a systematic evaluation and meta-analysis to determine the efficacy of platelet-rich plasma (PRP) treatment for patients with chronic low back pain. Comprehensive database searches were performed in four databases. This study was conducted and reported based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses Guideline and registered to PROSPERO. We included and examined randomized controlled trials that looked into research employing PRP for patients with chronic low back pain. Outcomes of interest include clinical enhancement of pain, which is demonstrated in pain scores. Three studies were included comprising 138 patients with chronic low back pain. After 1, 3, and 6 months after injection, there was a substantial reduction in the pain score difference between the PRP and control groups, demonstrating PRP's superiority over the control group in the treatment of chronic low back pain. PRP injection significantly enhances chronic low back pain in the first, third, and sixth months after injection compared to controls.
... The disc signal in the ADSC combined with PRP group showed higher intensity than that in the other groups ( Figure 6A) and was statistically significant in reversing disc degeneration ( Figure 6B) (111). Similar therapies based on the combination of PRP and stem cells have been reported in many studies (113)(114)(115)(116), and the biological efficacy of PRP has been confirmed in the experimental results. With the addition of PRP, many types of stem cells can differentiate into NP cell phenotype, and the diseased intervertebral disc can be reversed and regenerated to a certain extent, which provides a potential feasible scheme for future clinical treatment. ...
With the aging of the population and changes in lifestyle, the incidence of spine-related diseases is increasing, which has become a major global public health problem; this results in a huge economic burden on the family and society. Spinal diseases and complications can lead to loss of motor, sensory, and autonomic functions. Therefore, it is necessary to identify effective treatment strategies. Currently, the treatment of spine-related diseases includes conservative, surgical, and minimally invasive interventional therapies. However, these treatment methods have several drawbacks such as drug tolerance and dependence, adjacent spondylosis, secondary surgery, infection, nerve injury, dural rupture, nonunion, and pseudoarthrosis. Further, it is more challenging to promote the regeneration of the interstitial disc and restore its biomechanical properties. Therefore, clinicians urgently need to identify methods that can limit disease progression or cure diseases at the etiological level. Platelet-rich plasma (PRP), a platelet-rich form of plasma extracted from venous blood, is a blood-derived product. Alpha granules contain a large number of cytokines, such as platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), epidermal growth factor, platelet factor 4 (PF-4), insulin-like growth factor-1 (IGF-1), and transforming growth factor-β (TGF-β). These growth factors allow stem cell proliferation and angiogenesis, promote bone regeneration, improve the local microenvironment, and enhance tissue regeneration capacity and functional recovery. This review describes the application of PRP in the treatment of spine-related diseases and discusses the clinical application of PRP in spinal surgery.
... [36] Bunun yanında mezenkimal kök hücre (MSC)'lerle desteklenmiş trombositten zengin plazma (PRP), yan etki olmaksızın tavşan İDD modelinde onarımı indüklemiştir. [37] Ancak İVD avasküler bir dokudur. Dolayısıyla implante edilmiş ve rejenere edilmiş hücrelerin düşük glikoz, asidik ortam, hipoksi ve hipertonik ortama uyum sağlaması gerekir. ...
... Two and four weeks after PRP application, they found an increased DHI and signal intensity and elevated proteoglycan and COL II expression compared with the control group, which suggested that PRP intervention may be able to effectively suppress the IDD process. Wang et al. [39] injected PRP with bone marrow-derived MSCs (BMSCs) in a rabbit AF puncture model and found that the ECM and cell densities were well preserved and increased T2 signal intensity on MRI grading, while a strong immunopositive staining for COL II showed a poor AF recovery. The MRI scores of the PRP group were similar to those of the PRP+BMSC group at 2 weeks, yet the efficacy of PRP+BMSC was diminished at 8 weeks. ...
Intervertebral disc degeneration (IDD) is a globally occurring disease that represents a significant cause of socioeconomic problems. Currently, the main method for treating IDD is surgery, including discectomy and vertebral fusion. Several in vitro experiments demonstrated that platelet-rich plasma (PRP) could stimulate cell proliferation and extracellular matrix regeneration. Additionally, in vivo experiments have proven that PRP injection could restore intervertebral disc height. Clinical studies demonstrated that PRP injection could significantly relieve patient pain. However, further studies are still required to clarify the roles of PRP in IDD prevention and treatment. This review is aimed at summarizing and critically analyzing the current evidence regarding IDD treatment with PRP.
... Although outside the scope of our current study, bone marrow-derived stem cells have had positive effects in the treatment of degenerative disc disease in both preclinical and clinical settings, and as such, the scaffold used in IVD regenerative treatment must be able to provide a suitable environment for the growth and differentiation of these cells. [13][14][15] Chitosan has shown the ability to provide an appropriate medium for mesenchymal stem cell differentiation. 16 Chitosan-based nanoparticles may also assist in the reduction of inflammation associated with disc damage. ...
Background:
The purpose of our study was to examine the effect of controlled delivery of TGF-β3, BMP-4, and TIMP-2 with a biocompatible biopolymer, chitosan, on an acutely injured intervertebral disc (IVD) in a rabbit model.
Methods:
After conducting an in vitro analysis of the chondrogenic capacity of the biomolecule cocktail use (ie, TGF-β3, BMP-4, and TIMP-2) and confirming stem cell viability in chitosan hydrogel, 15 New Zealand white rabbits underwent a lateral approach of the L1 to L4 IVDs. In each rabbit, the L2 to L3 IVD was left pristine, whereas the L1 to L2 and the L3 to L4 IVDs in each rabbit underwent nucleotomy via a 25-G needle, and the animal was subsequently randomized to no further treatment (defect only), chitosan alone, Chitosan + TGF-β3 + BMP-4, or chitosan + TGF-β3 + BMP-4 + TIMP-2. At 6 weeks after injury and intervention, the rabbits were killed and spines harvested to undergo quantitative T2 magnetic resonance imaging (MRI) and subsequent histologic analysis.
Results:
In the in vitro analysis, cells treated with experimental media containing TGF-β3, BMP-4, and TIMP-2 exhibited staining indicative of GAG production and began to exhibit a chondrocytic morphology. Quantitative T2 MRI mapping demonstrates that discs treated with chitosan, chitosan containing TGF-β3 and BMP-4, or chitosan containing TGF-β3, BMP-4, and TIMP-2 had consistently higher T2 relaxation times compared with defect-only discs. When the T2 relaxation times of each treatment group and defect-only discs were normalized to the healthy control disc, it was found that the T2 relaxation time of discs treated with chitosan containing TGF-β3 and BMP-4 and discs treated with chitosan containing TGF-β3, BMP-4, and TIMP-2 were significantly greater compared with defect-only discs (P = .048 and P = .013, respectively). Histologically, animals that received chitosan only, or chitosan with TGF-β3 and BMP-4, showed a significantly higher intensity of Safranin-O staining (P = .016 and P = .02, respectively) compared with control discs, whereas the difference in staining intensity in animals that received chitosan loaded with TGF-β3, BMP-4, and TIMP-2 failed to achieve significance (P = .161).
Conclusions:
A combination of chitosan, TGF-β3, and BMP-4 was effective at promoting regeneration in an acute disc injury rabbit model, whereas TIMP-2 did not have a significant effect.
... An intervertebral disc (IVD) is a pad of cartilage between two adjacent vertebrae that acts as a shock absorber. It plays a vital role in stabilization as well as flexion and extension of the spine [29]. ...
... It is supplied by branches of the metaphyseal arteries around the outer annulus [30]. Since the IVD lacks a proper nutritional supply of growth factors, it has minimum self-repairing ability [29,31]. ...
... The patient presents with pain that may radiate [32]. Current treatment options include conservative approaches such as anti-inflammatory drugs and physiotherapy, as well as spinal surgery [29]. Not only do current treatments completely ignore the underlying cause but treatment options like surgery restrict patient mobility and can interrupt their daily activity for nearly 6 weeks [32]. ...
Low back pain (LBP) is a common problem encountered by physicians. It is a considerable cause of morbidity and socioeconomic loss and is one of the most expensive musculoskeletal disorders. Conventional treatments include bed rest, analgesics, therapeutic exercises, lumbar or caudal epidural corticosteroids, and surgery. Several new biological therapies are being investigated for use in LBP and one of these is platelet-rich plasma (PRP). In this article, we summarize the current literature published on PRP concerning its composition, classification, and application in LBP. We believe our review will prove useful to clinicians and academics alike, interested in new developing therapies for LBP.
