关节腔内注射PRP与HA治疗膝关节骨性关节炎的荟萃分析

[目的]通过荟萃分析比较关节腔内注射富血小板血浆(PRP)与透明质酸(HA)治疗膝关节骨性关节炎的疗效差异。[方法]检索并收集2008年1月～2018年9月公开发表于Embase、Pubmed、Cochrane、中国知网(CNKI)、中文科技期刊全文数据库(VIP)及万方数据库关于关节腔内注射PRP与HA治疗膝关节骨性关节炎的随机对照研究文章,严格按照纳入和排除标准及文献质量评分标准收集数据,运用Review Manager5.3软件对数据进行荟萃分析。[结果]共纳入19篇文献,总计2 114例接受关节腔药物治疗的膝骨关节炎患膝,其中PRP组1 079例,HA组1 035例。治疗后12个月时,PRP组WOMAC评分低于HA组[MD=-10.30, 95%CI (-14.27～-6.34),P0.01];PRP组IKDC评分高于HA组[MD=7.56, 95%CI (3.61～11.68),P0.01];PRP组Lequesne指数评分低于HA组[MD=-3.63, 95%CI (-7.16,～-0.11),P=0.04];而两组间VAS评分差异无统计学意义(P0.05)。[结论]关节腔内注射PRP治疗膝骨关节炎疗效显著,在远期疗效PRP较HA具有更好的优势,可以减轻膝关节疼痛,改善膝关节功能,提高生活质量。     

骨髓间充质干细胞浓缩上清液对骨性关节炎大鼠模型治疗作用的初步研究

[目的]探讨骨髓间充质干细胞(MSCs)浓缩上清液对骨性关节炎大鼠的治疗作用。[方法]取SD大鼠骨髓,筛选、纯化并鉴定MSCs,SDS-PAGE电泳初步了解培养后上清液所含可溶性蛋白的分子量。动物分组:造模组、正常对照组、造模MSCs上清液治疗组、造模L-DMEM培养液对照组。MSCs浓缩上清液治疗后分不同时间段分别测量大鼠体重、踝关节周长和后足爪体积,同时观察大鼠食欲、活动情况及毛色等,治疗后4周四肢踝关节病理检查。[结果](1)成功分离培养并鉴定了MSCs,SDS-PAGE电泳示MSCs上清液中含18.4~25 KDa的蛋白物质;(2)骨性关节炎大鼠动物模型用上述MSCs上清液治疗4周,原发病变缓解,关节滑膜病理检查均未见明显异常,体重增长等指标接近生理盐水对照组,与造模组大鼠相比,体重、足爪体积以及踝关节周长差异有统计学意义(P<0.05),而造模L-DMEM对照组,各参数与造模组大鼠相比差异无统计学意义。[结论]MSCs上清液中存在治疗骨性关节炎大鼠模型的可溶性细胞因子,并能有效减轻关节肿胀情况。     

Randomized clinical trial: expanded autologous bone marrow mesenchymal cells combined with allogeneic bone tissue,compared with autologous iliac crest graft in lumbar fusion surgery

BACKGROUND CONTEXTAlthough autogenous iliac crest bone graft (AICBG) is considered the gold-standard graft material for spinal fusion, new bone substitutes are being developed to avoid associated complications and disadvantages. By combining autologous bone marrow mesenchymal stromal cells (MSCs) expanded ex vivo and allogenic cancellous bone graft, we obtain a tissue-engineered product that is osteoconductive and potentially more osteogenic and osteoinductive than AICBG, owing to the higher concentration of MSCs.PURPOSEThis study aimed to evaluate the feasibility and safety of implanting a tissue-engineered product consisting of expanded bone marrow MSCs loaded onto allograft bone (MSC+allograft) for spinal fusion in degenerative spine disease, as well as to assess its clinical and radiological efficacy.STUDY DESIGN/SETTINGA prospective, multicenter, open-label, blinded-reader, randomized, parallel, single-dose phase I-II clinical trial.PATIENT SAMPLEA total of 73 adult patients from 5 hospitals, with Meyerding grade I-II L4–L5 degenerative spondylolisthesis and/or with L4–L5 degenerative disc disease who underwent spinal fusion through transforaminal lumbar interbody fusion (TLIF).OUTCOME MEASURESSpinal fusion was assessed by plain X-ray at 3, 6, and 12 months and by computed tomography (CT) at 6 and 12 months post-treatment. An independent radiologist performed blinded assessments of all images. Clinical outcomes were measured as change from baseline value: visual analog scale for lumbar and sciatic pain at 12 days, 3, 6, and 12 months posttreatment, and Oswestry Disability Index and Short Form-36 at 3, 6, and 12 months posttreatment.METHODSPatients who underwent L4–L5 TLIF were randomized for posterior graft type only, and received either MSC+allograft (the tissue-engineered product, group A) or AICBG (standard graft material, group B). Standard graft material was used for anterior fusion in all patients. Feasibility was measured primarily as the percentage of randomized patients who underwent surgery in each treatment group. Safety was assessed by analyzing treatment-emergent adverse events (AEs) for the full experimental phase and appraising their relationship to the experimental treatment. Outcome measures, both radiological and clinical, were compared between the groups.RESULTSSeventy-three patients were randomized in this study, 36 from the MSC+allograft group and 37 from the AICBG group, and 65 were surgically treated (31 group A, 34 group B). Demographic and comorbidity data showed no difference between groups. Most patients were diagnosed with grade I or II degenerative spondylolisthesis. MSC+allograft was successfully implanted in 86.1% of randomized group A patients. Most patients suffered treatment-emergent AEs during the study (88.2% in group A and 97.1% in group B), none related to the experimental treatment. X-ray-based rates of posterior spinal fusion were significantly higher for the experimental group at 6 months (p=.012) and 12 months (p=.0003). CT-based posterior fusion rates were significantly higher for MSC+allograft at 6 months (92.3% vs 45.7%; p=.0001) and higher, but not significantly, at 12 months (76.5% vs 65.7%; p=.073). CT-based complete response (defined as the presence of both posterior intertransverse fusion and anterior interbody fusion) was significantly higher at 6 months for MSC+allograft than for AICBG (70.6% vs 40%; p=.0038), and remained so at 12 months (70.6% vs 51.4%; p=.023). Clinical results including patient-reported outcomes improved postsurgery, although there were no differences between groups.CONCLUSIONSCompared with the current gold standard, our experimental treatment achieved a higher rate of posterior spinal fusion and radiographic complete response to treatment at 6 and 12 months after surgery. The treatment clearly improved patient quality of life and decreased pain and disability at rates similar to those for the control arm. The safety profile of the tissue-engineered product was also similar to that for the standard material, and no AEs were linked to the product. Procedural AEs did not increase as a result of BM aspiration. The use of expanded bone marrow MSCs combined with cancellous allograft is a feasible and effective technique for spinal fusion, with no product-related AEs found in our study.     

Intraarticular injection autologous platelet‐rich plasma and bone marrow concentrate in a goat osteoarthritis model

To evaluate the effects of intraarticular injections of autologous platelet‐rich plasma (PRP) or bone marrow concentrate (BMC) on osteoarthritis (OA), 24 adult goats were equally divided into control (Ctrl), saline (NS), PRP, and BMC groups, and OA was induced by surgery in NS, PRP, and BMC groups. Autologous PRP and BMC were obtained from whole blood and bone marrow aspirates, respectively. The data revealed, platelets were increased in BMC by 1.8‐fold, monocytes by 5.6‐fold, TGF‐β1 by 7.7‐fold, and IGF‐1 by 3.6‐fold (p < 0.05), and platelets were increased in PRP by 2.9‐fold, and TGF‐β1 by 3.3‐fold (p < 0.05). From the sixth week post‐operation, saline, PRP, and BMC were administered by intraarticular injection once every 4 weeks, three consecutive times. After the animals were sacrificed, inflammatory cytokines in the synovial fluid was measured, and bone and cartilage degeneration progression was observed by macroscopy, histology, and immunohistochemistry. Compared with the NS group, the level of inflammatory cytokines was reduced in the PRP and BMC groups (p < 0.05). Histologically, delayed cartilage degeneration and higher levels of extracellular matrix (ECM) were observed in both PRP and BMC treated groups (p < 0.05). Furthermore, the BMC group showed greater cartilage protection and less ECM loss than the PRP group (p < 0.05). In summary, this study showed that intraarticular injection of autologous PRP and BMC has therapeutic efficacy in a goat osteoarthritis model, with the greater benefit in terms of cartilage protection being observed in the BMC‐treated group than PRP. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2140–2146, 2018.

     

Intra-articular sodium hyaluronate in osteoarthritis of the knee: a multicenter, double-blind study

The efficacy and the safety of intra-articular injections of sodium hyaluronate were studied in patients with osteoarthritis of the knee in a randomized multicenter double-blind study. Two hundred and nine patients received five injections of either 25 mg hyaluronate/2.5 ml (verum, N = 102) or 0.25 mg hyaluronate/2.5 ml (control, N = 107) at weekly intervals. Seven patients in each group were excluded from the protocol-correct efficacy analysis. The Lequesne Index, the first main criterion, showed a significant superiority of the verum-treated patients after the third injection up to the final follow-up examination 9 weeks after the last injection (MANOVA, P < 0.025). The consumption of paracetamol was defined as a complementary main criterion that did not reveal significant differences between the treatment groups. Most of the individual secondary endpoints demonstrated a much better response to the active treatment without reaching the significance level in the intergroup comparisons for the single time-points. Side-effects were confined to local reactions of minor severity and short duration in four patients (six events) of the verum group and in five patients of the control group. Clinical chemistry and hematology remained essentially unchanged.     

Human autologous culture expanded bone marrow mesenchymal cell transplantation for repair of cartilage defects in osteoarthritic knees

OBJECTIVE: There is no widely accepted method to repair articular cartilage defects. Bone marrow mesenchymal cells have the potential to differentiate into bone, cartilage, fat and muscle. Bone marrow mesenchymal cell transplantation is easy to use clinically because cells can be easily obtained and can be multiplied without losing their capacity of differentiation. The objective of this study was to apply these cell transplantations to repair human articular cartilage defects in osteoarthritic knee joints. DESIGN: Twenty-four knees of 24 patients with knee osteoarthritis (OA) who underwent a high tibial osteotomy comprised the study group. Adherent cells in bone marrow aspirates were culture expanded, embedded in collagen gel, transplanted into the articular cartilage defect in the medial femoral condyle and covered with autologous periosteum at the time of 12 high tibial osteotomies. The other 12 subjects served as cell-free controls. RESULTS: In the cell-transplanted group, as early as 6.3 weeks after transplantation the defects were covered with white to pink soft tissue, in which metachromasia was partially observed. Forty-two weeks after transplantation, the defects were covered with white soft tissue, in which metachromasia was observed in almost all areas of the sampled tissue and hyaline cartilage-like tissue was partially observed. Although the clinical improvement was not significantly different, the arthroscopic and histological grading score was better in the cell-transplanted group than in the cell-free control group. CONCLUSIONS: This procedure highlights the availability of autologous culture expanded bone marrow mesenchymal cell transplantation for the repair of articular cartilage defects in humans.     

重度膝骨关节炎患者骨髓水肿与骨质疏松的相关性研究

目的:探讨重度膝骨关节炎患者骨髓水肿与骨质疏松的关系。方法:采用非匹配型病例对照研究,自2020年1月至2021年3月收治已行膝关节MRI及双能X线吸收测定法(dualenergy X-ray absorptiometry,DXA)骨密度(bone mineral density,BMD)检查的160例重度膝骨关节炎患者,其中合并骨髓水肿的患者80例为骨髓水肿组,不合并骨髓水肿的患者80例为无骨髓水肿组。骨髓水肿组男12例,女68例;年龄51～80(66.58±8.10)岁;病程5～40(15.61±9.25)个月;身体质量指数(body mass index,BMI)21.81～34.70(27.79±3.00) kg·m^-2;Kellgren-Lawrence(K-L)分级,Ⅲ级25例,Ⅳ级55例。无骨髓水肿组男15例,女65例;年龄50～80 (67.82±8.05)岁;病程6～37(15.75±8.18)个月;BMI 21.39～34.46(28.26±3.13) kg·m^-2;K-LⅢ级38例,Ⅳ级42例。采用膝关节整体磁共振成像评...     

骨髓间充质干细胞对膝关节炎大鼠软骨损伤及KDM6A/SOX9信号通路的影响

目的 观察骨髓间充质干细胞对膝关节骨性关节炎大鼠的影响,并探讨其机制。方法 将40只SD大鼠随机分为正常对照组(Control)、膝关节骨性关节炎组(KOA)、骨髓间充质干细胞组(BMSCs),每组10只,剩余10只用于骨髓间充质干细胞的分离。处理4周后进行大鼠关节指数(AI)评分;HE染色观察软骨组织病理学变化;免疫组化检测软骨组织Col II、IL-6、MMP-3、MMP-13表达;ELISA法检测血清IL-6、TNF-α、MMP-3、MMP-13含量;qRT-PCR检测软骨组织Col II、Col I、TNF-α、IL-6、MMP-13、KDM6A、SOX9、Aggrecan mRNA表达;Western blot检测软骨组织KDM6A、SOX9、Aggrecan蛋白表达。结果 与Control组比较,KOA组大鼠AI评分、血清IL-6、TNF-α、MMP-3、MMP-13含量、软骨组织IL-6、MMP-3、MMP-13表达明显升高(P<0.05);Col II、KDM6A、Aggrecan、SOX9 mRNA和蛋白表达明显降低(P<0.05)。与KOA组比较,BMS...     

Intra-arterial infusion of autologous bone marrow mononuclear cells in patients with moderate to severe middle cerebral artery acute ischemic stroke

Transplantation of autologous bone marrow mononuclear cells (BMMCs) has been proven safe in animal and human studies. However, there are very few studies in stroke patients. In this study, intra-arterial autologous BMMCs were infused in patients with moderate to severe acute middle cerebral artery infarcts. The subjects of this study included 20 patients with early or late spontaneous recanalization but with persistent deficits, in whom treatment could be initiated between 3 and 7 days after stroke onset. Mononuclear cells were isolated from bone marrow aspirates and infused at the proximal middle cerebral artery of the affected hemisphere. Safety analysis (primary endpoint) during the 6-month follow-up assessed death, any serious clinical events, neurological worsening with ≥ 4-point increase in National Institutes of Health Stroke Scale (NIHSS) scores, seizures, epileptogenic activity on electroencephalogram, and neuroimaging complications including new ischemic, hemorrhagic, or neoplastic lesions. Satisfactory clinical improvement (secondary endpoint) at 90 days was defined according to the pretreatment NIHSS scores as follows: modified Rankin Scale score of 0 in patients with NIHSS <8, modified Rankin Scale scores of 0-1 in patients with NIHSS 8-14, or modified Rankin Scale scores 0-2 in patients with NIHSS >14. Good clinical outcome was defined as mRS ≤2 at 90 days. Serial clinical, laboratory, electroencephalogram, and imaging evaluations showed no procedure-related adverse events. Satisfactory clinical improvement occurred in 6/20 (30%) patients at 90 days. Eight patients (40%) showed a good clinical outcome. Infusion of intra-arterial autologous BMMCs appears to be safe in patients with moderate to severe acute middle cerebral artery strokes. No cases of intrahospital mortality were seen in this pilot trial. Larger prospective randomized trials are warranted to assess the efficacy of this treatment approach.     

Effect of autologous bone marrow derived mesenchymal stem cells in treatment of rheumatoid arthritis

IntroductionChronic inflammation causes articular bone and cartilage degeneration in people with rheumatoid arthritis (RA). Despite recent advancements in the management of RA, adverse side effects and ineffective treatments remain a problem. Effective treatment is usually hampered by financial issues. As a result, less expensive medications that reduce both inflammation and bone resorption are required. Mesenchymal stem cells (MSCs) have recently been identified as a potential therapy for RA.Aim of the studyThis study aimed to examine the anti-arthritic effect of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides (Os), and human placental extract (HPE), individually and combined, on an RA model, using Complete Freund's adjuvant (CFA)-induced arthritis in rats.Materials and methodsIn female rats, RA was induced by injecting CFA in the paw of the hind limb. Rat bone marrow-MSCs, oligosaccharides, and human placental extract (HPE) were given individually and in combination via the intraperitoneal route. A complete blood count (CBC), erythrocyte sedimentation rate (ESR), serum cortisol, urea, uric acid, and other biochemical parameters were measured to determine the safety and efficacy of the different treatments. Histopathological analysis of bone sections was carried out.ResultsCombining oligosaccharides and HPE therapy with the infusion of rat-bone marrow MSCs had beneficial antiarthritic and anti-inflammatory effects in CFA-induced arthritis in rats: overall such triple therapy significantly reduced serum levels of IL-6, IL-10, and TNF-alpha in comparison with all other combinations (all P > 0.05). Meanwhile, the triple therapy did not have negative effects on levels of CBC, serum cortisol, ESR, and liver enzymes (all NS) as well as on renal functions (NS). Also, the histopathological analysis showed significant improvements in the healing and remodelling of osteoporotic lesions in arthritic rats. As shown by counting apoptotic cells as a histopathological substitute for measuring apoptotic or regeneration markers, the lowest count was found in the group treated with a triple therapy of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs), oligosaccharides, and HPE.ConclusionThe combination of rat MSCs, oligosaccharides, and HPE has the potential to be an effective treatment for rheumatoid arthritis.     

Use of bone marrow derived mesenchymal stem cells for the treatment of osteoarthritis: A retrospective long-term follow-up study

BackgroundAvailable studies suggest that bone marrow concentrate, highly enriched in mesenchymal stem cells, is a potentially encouraging treatment for knee osteoarthritis. The aim of this retrospective study was to evaluate the clinical outcome in patients affected by this condition after treatment with autologous bone marrow aspirate concentrate (BMAC).Methods55 patients who had undergone a single intra-articular injection of BMAC were administered two questionnaires to clinically evaluate their condition based on patient-reported outcome measures before treatment and at follow-up.ResultsAnalysis of the data collected indicates that patients experienced improvements in Tegner, VAS and WOMAC scores and that all outcomes at the follow-up improved in a statistically significant manner compared to outcomes at baseline.ConclusionsThe changes observed in the different scores examined suggest that a single BMAC injection seems to be a beneficial and safe treatment for knee osteoarthritis.     

成人间充质干细胞体外成骨的初步研究

目的 建立一种分离和培养成人骨髓来源的间充质干细胞（MSCs）的方法,观察成人MSCs体外成骨潜能。方法 用Percoll分离液分离出骨髓中的单个核细胞,并在含10％胎牛血清的低糖DMEM培养液中培养。通过传代培养扩增MSCs。为促进成人MSCs体外成骨性分化,第5传代培养时加入成骨性添加剂,培养第4、12天分别用流式细胞仪分析成人MSCs表面分子的表达,并用碱性磷酸酶组化染色和Von Kossa染色。结果 成人MSCs是骨髓黏附细胞中有相应细胞表面蛋白表达和形态均的一细胞群。成骨性添加剂可作用于传代培养的成人MSCs,表现为培养皿表面有相互连接的结节状聚合体、碱酶染色阳性细胞数量增多、Von Kossa染色可见钙化的基质沉积。结论 所建立的成人MSCs的分离和培养条件可分选出骨髓黏附细胞中一组独特的细胞群,成人MSCs具有体外成骨潜能。     

Unicameral bone cysts: a comparison of injection of steroid and grafting with autologous bone marrow

Open surgery is rarely justified for the initial treatment of a unicameral bone cyst, but there is some debate concerning the relative effectiveness of closed methods. This study compared the results of steroid injection with those of autologous bone marrow grafting for the treatment of unicameral bone cysts. Between 1990 and 2001, 30 patients were treated by steroid injection and 28 by grafting with autologous bone marrow. The overall success rates were 86.7% and 92.0%, respectively (p>0.05). The success rate after the initial procedure was 23.3% in the steroid group and 52.0% in those receiving autologous bone marrow (p<0.05), and the respective cumulative success rates after second injections were 63.3% and 80.0% (p>0.05). The mean number of procedures required was 2.19 (1 to 5) and 1.57 (1 to 3) (p<0.05), the mean interval to healing was 12.5 months (4 to 32) and 14.3 months (7 to 36) (p>0.05), and the rate of recurrence after the initial procedure was 41.7% and 13.3% in the steroid and in the autologous bone marrow groups, respectively (p<0.05). Although the overall rates of success of both methods were similar, the steroid group had higher recurrence after a single procedure and required more injections to achieve healing.     

骨形态发生蛋白2基因修饰自体骨髓间充质干细胞移植促进兔胫骨牵张成骨的实验研究

[目的]观察人骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞移植对兔胫骨牵张成骨新骨形成的促进作用。[方法]48只新西兰白兔随机摸球法分为3组。建立牵张成骨动物模型,在固定期第2 d,实验组于牵张间隙注射人骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞;对照组注射等量自体骨髓间充质干细胞;空白组不注射任何物质。[结果]在固定期2周及6周实验组牵张区在大体观察、HE染色、X线观察方面成骨质量均好于对照组和空白组。12周后取牵张成骨区标本作骨组织骨密度和生物力学测定,结果显示实验组新生骨质量较高,骨愈合情况要优于对照组和空白组。[结论]骨形态发生蛋白2基因修饰的自体骨髓间充质干细胞移植能有效提高兔胫骨牵张成骨新骨形成质量。     

Cultured autologous human cells for hard tissue regeneration: preparation and characterization of mesenchymal stem cells from bone marrow

Mesenchymal stem cells (MSCs) are multipotent cells and can be induced in vitro and in vivo to differentiate not only into the variety of mesodermal cells, but into either ectodermal or endodermal cells. This capability indicates the usefulness of MSCs for tissue engineering. Cell surface antigen analyses using various types of CD antibodies demonstrated that adherent fibroblastic cells derived from fresh human bone marrow are mesenchymal types and the cells showed extensive capability for proliferation and/or differentiation. We labeled the adherent cultured marrow cells as MSCs and, significantly, found the MSCs could even proliferate from aged marrow cells. After about sixteen days of culturing, we were able to harvest 100 million MSCs from only 3 ml of fresh human marrow. Moreover, the MSCs could be cryopreserved at -80 degrees C without noticeable loss of viability and capability of osteoblastic differentiation. These results indicate that MSCs hold promise for utilization in hard tissue regeneration.     

Umbilical cord-derived mesenchymal stem cells for treating osteoarthritis of the knee: a single-arm,open-label study

European Journal of Orthopaedic Surgery & Traumatology - Despite being a common cause of quality-of-life impairment, there are no efficacious therapies that could prevent the progression of...