This trial pretends to validate for clinical use a bioengineered product composed of MSV cells (mesenchymal stem cells produced by IBGM, Valladolid, which have already been approved by the Spanish Regulatory Agency for three previous clinical trials) and a cross-linked matrix of autologous plasma patented by The Blood and Tissue Bank of Asturias (WO2008/ 119855) for bone maxillary cysts refilling. These two groups collaborate in the present project with the team of Maxillofacial Surgery of the Hospital Universitario del Río Hortega, who leads the clinical trial and deals with the medical aspects. The proposed trial is based on positive results obtained in previous animal studies performed by the present multidisciplinary team. The investigators propose a phase I / II clinical trial with 10 patients suffering from bone cysts in the maxillofacial region. Autologous mesenchymal stem cells isolated from a bone marrow sample will be seeded in the autologous plasma matrix and cultivated for 3 weeks. At this time, the cyst will be removed by surgery and the cavity filled with the protein matrix containing the mesenchymal cells. Checks will be conducted at 3 weeks, 3 and 6 months following the evolution of the cavity by panoramic radiography and computerized tomography scan.

开始日期2011-04-01

申办/合作机构

Red De Terapia Celular

[+2]

100 项与 MSCs therapy(University of Valladolid) 相关的临床结果

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100 项与 MSCs therapy(University of Valladolid) 相关的转化医学

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100 项与 MSCs therapy(University of Valladolid) 相关的专利（医药）

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2,695

项与 MSCs therapy(University of Valladolid) 相关的文献（医药）

2024-12-01·Current Stem Cell Research & Therapy

Fucoxanthin Enhances the Antifibrotic Potential of Placenta-derived Mesenchymal Stem Cells in a CCl4-induced Mouse Model of Liver

Article

作者: Grebnev, Dmitry ; Beresneva, Olga ; Gavrilov, Ilya ; Konyshev, Konstantin ; Slautin, Vasilii ; Maklakova, Irina

Background:The effectiveness of fucoxanthin (Fx) in liver diseases has been reported due to its anti-inflammatory and antifibrotic effects. Mesenchymal stem cells (MSCs)-based therapy has also been proposed as a promising strategy for liver fibrosis treatment. Recent studies have shown that the co-administration of MSCs and drugs demonstrates a pronounced effect on liver fibrosis.Aim:This study aimed to determine the therapeutic potential of placenta-derived MSCs (PD-MSCs) in combination with Fx to treat liver fibrosis and evaluate their impact on the main links of liver fibrosis pathogenesis.Methods:After PD-MSCs isolation and identification, outbred ICR/CD1 mice were divided into five groups: Control group, CCl4 group (CCl4), Fx group (CCl4+Fx), PD-MSCs group (CCl4+MSCs) and cotreatment group (CCl4+MSCs+Fx). Biochemical histopathological investigations were performed. Semiquantitative analysis of the alpha-smooth muscle actin (α-SMA+), matrix metalloproteinases (MMP-9+, MMP-13+), tissue inhibitor of matrix metalloproteinases-1 (TIMP-1+) areas, and the number of positive cells in them were studied by immunohistochemical staining. Transforming growth factor-beta (TGF-β), hepatic growth factor (HGF), procollagen-1 (COL1α1) in liver homogenate and proinflammatory cytokines in blood serum were determined using an enzyme immunoassay.Results:Compared to the single treatment with PD-MSCs or Fx, their combined administration significantly reduced liver enzyme activity, the severity of liver fibrosis, the proinflammatory cytokine levels, TGF-β level, α-SMA+, TIMP-1+ areas and the number of positive cells in them, and increased HGF level, MMP-13+, and MMP-9+ areas.Conclusion:Fx enhanced the therapeutic potential of PD-MSCs in CCl4-induced liver fibrosis, but more investigations are necessary to understand the mutual impact of PD-MSCs and Fx.

2024-12-01·Techniques in Coloproctology

Closing the internal opening with a rectal advancement flap increases the efficacy of mesenchymal stem cell injection for complex Crohn's disease anal fistulas

Article

作者: Alam, A ; de Parades, V ; Barré, A ; Far, E Safa ; Spindler, L ; Fathallah, N ; Haouari, M A ; Roland, D

BACKGROUNDThe efficacy of injections of mesenchymal stem cells (MSC) for anal fistula treatment may be impaired by the persistence of stools passing into the fistula, causing bacterial contamination and a local inflammatory reaction. We aimed to compare remission rates between patients treated by MSC injection with simple sutures and those treated with a rectal advancement flap.METHODSThis single-center prospective study compared the first patients who underwent internal opening closure with sutures with the subsequent patients treated with a flap. Complete clinical remission was defined as complete closure of the external opening(s) without pain or discharge, and complete radiological remission was defined as a Magnifi-CD score of 0.RESULTSWe compared the first 42 patients who had sutures with the 20 subsequent patients who had an advancement flap. The median follow-up was 15.5 [8.8-24.9] months. The cumulative incidence of complete clinical response at M12 was 53.8% [38.1-69.6%] in the suture group versus 93.3% [77.4-100.0] in the flap group (p < 0.001). The Magnifi-CD score was 0 for 41.7% [25.5-59.2%]) of patients treated with sutures versus 72.7% [39.0-63.9%]) of patients treated with a flap (p = 0.093). Anal incontinence score did not differ between the two groups. Practicing an advancement flap was the only significant factor associated with complete clinical remission over time (adjusted HR [95% CI] of 2.6 [1.4-4.9], p = 0.003).CONCLUSIONSComplete clinical remission rates following MSC injection are significantly higher after closure of the internal opening with a rectal flap than after closure with sutures, without consequences on anal continence.

2024-10-01·Osteoarthritis and Cartilage

Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials

Review

作者: Poolman, Rudolf W ; Busse, Jason W ; Burnham, Robert ; Momenilandi, Feryal ; Khosravirad, Azin ; Zandieh, Sara ; Sofi-Mahmudi, Ahmad ; Sadeghirad, Behnam ; Rehman, Yasir ; Patel, Mansi ; Jomy, Jane ; Couban, Rachel J

OBJECTIVETo assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA).METHODSWe searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence.RESULTSWe included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty).CONCLUSIONSIntra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function.

项与 MSCs therapy(University of Valladolid) 相关的新闻（医药）

2024-01-06

·生物探索

JAMA Oncology | 陆军军医大学高力/张曦发现间充质干细胞预防单倍体造血干细胞移植后的慢性移植物抗宿主病

慢性移植物抗宿主病(GVHD)限制了单倍体造血干细胞移植(HSCT)的长期获益。2023年12月28日，陆军军医大学高力及张曦共同通讯在JAMA Oncology（IF=28）在线发表题为“Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant”的研究论文，该研究评估了在单倍造血干细胞移植后早期(45天和100天)反复输注脐带间充质干细胞(MSCs)预防慢性GVHD的效果。158例患者中，女性58例(36.7%)；MSC组和对照组的中位(范围)年龄分别为28(18-60)岁和28(18-56)岁。共筛选158例患者，148例患者在输注MSCs前1天随机分为MSC组(n=74)和对照组(n=74)。估计重度慢性GVHD的2年累积发病率在MSC组为5.4%(95% CI, 1.8%-14.0%)，在对照组为17.4%(95% CI, 10.1%-28.5%)(风险比[HR]， 0.29;95% CI, 0.10-0.88;P = .03)。在白血病复发的累积发生率方面，MSC组与对照组无差异(HR, 1.17;95% CI, 0.55-2.47;P = .68)。骨髓间充质干细胞组II ~ IV期急性GVHD累计发生率显著低于对照组(HR, 0.25;95% CI, 0.09-0.67;P = 0.01)。MSC组无GVHD和无复发生存率优于对照组(HR, 0.62;95% CI, 0.39-0.98;P =0.04)。该随机临床试验结果显示，早期反复输注MSCs可降低慢性GVHD的发病率和严重程度，急性GVHD的发病率和严重程度表现为单倍造血干细胞移植后患者更好的无GVHD和无复发生存率。慢性移植物抗宿主病(cGVHD)是同种异体造血干细胞移植(alloo-HSCT)后最常见的并发症，严重影响患者的生活质量。基于移植后以环磷酰胺(PTCy)和抗胸腺细胞球蛋白(ATG)为基础的预防方案，单倍体同种异体造血干细胞(haploo-HSCT)的发展可以挽救没有人类白细胞抗原(HLA)相同供体的患者的生命。然而，HLA错配增加了移植物抗宿主病(GVHD)的风险，因为急性GVHD(aGVHD)的发病率为40%至50%，cGVHD的发病率为50%至60%。更好的移植物白血病(GVL)效果已经在体内和临床试验样本中显示出来。对于单倍造血干细胞移植后的患者，报告的复发率相似，并且由于控制GVHD所需的免疫抑制增强，总生存率(OS)低于HLA相同的HSCT后的患者。对于cGVHD，无论进行何种治疗，一旦发生cGVHD，随访期间死亡率均超过30%。由于间充质间质细胞(MSCs)的治疗效果已在多项临床试验中得到证实，因此，MSCs可能是一种潜在的治疗GVHD和保持GVL效果的材料，其表现为移植受体无GVHD和无复发生存率(GRFS)的提高。为了有效预防cGVHD，作者团队在一项随机临床试验中探索了单倍造血干细胞移植后100天开始反复输注MSCs对cGVHD的预防效果，该试验显著降低了cGVHD的发病率和严重程度(27.4% vs 49.0%;P=.02)，排除了几乎所有发生GVHD的患者。根据一项针对GVHD患者间充质干细胞的荟萃分析的中等良好结果，MSCs输注的时机非常重要，可以促进不同的预防效果因此，该研究纳入了所有具有cGVHD风险的患者，旨在探索移植后早期(45天至81天)的新输注时间，以包括所有可能发生cGVHD的患者。严重慢性移植物抗宿主病(cGVHD)、cGVHD和复发的累积发病率（图源自JAMA Oncology）为了进一步提高MSCs的预防作用，在单倍造血干细胞移植后的早期输注UC-MSCs。与对照方案相比，该方案显著减少了cGVHD的总病例数和严重病例数，白血病复发率发生率相似。与其他免疫抑制GVHD预防方案相比，该方案的aGVHD发生率相似，且显著提高了cGVHD的发生率。该随机临床试验提示MSCs对cGVHD和aGVHD的预防作用，这可能增强单倍造血干细胞系统对cGVHD的预防作用。传统免疫抑制药物的加入使得感染难以避免，尤其是病毒感染。在该试验中，输注对巨细胞病毒或EBV的再激活没有显著影响，这两种病毒感染的再激活发生率均约为40%。在T细胞耗尽的单倍同型造血干细胞移植中，EBV的发病率增加(约90%)可能导致致命的淋巴细胞增生性疾病。在一项低剂量PTCy联合ATG/粒细胞集落刺激因子的试验中，CMV再激活发生率为73%，这需要额外的类似CMV的细胞毒性T淋巴细胞策略来预防CMV疾病在本试验中，数据显示输注MSCs并未增加AEs和严重AEs的总发生率。此外，MSC输注对出血性膀胱炎治疗有益，这可能与MSCs的组织修复作用有关。一般来说，MSC输注在临床应用中耐受性良好，易于管理，并且不需要其他预防或先发制人的干预治疗相关并发症。总的来说，单倍造血干细胞移植后45天开始反复输注MSCs是预防cGVHD和aGVHD的合适策略，它成功地提高了接受单倍造血干细胞移植的患者的GRFS。由于MSCs的阳性特性和安全性，MSC输注可与其他GVHD预防方案联合设计，如低剂量PTCy和T细胞耗尽的单倍同型HSCT，进一步降低单倍同型HSCT后GVHD的发生率，提高受者的预期寿命和生活质量。参考文献：Huang R, Chen T, Wang S, Wang J, et al. Mesenchymal Stem Cells for Prophylaxis of Chronic Graft-vs-Host Disease After Haploidentical Hematopoietic Stem Cell Transplant: An Open-Label Randomized Clinical Trial. JAMA Oncol. 2023 Dec 28. doi: 10.1001/jamaoncol.2023.5757. Epub ahead of print. PMID: 38153755.责编|探索君排版|探索君文章来源|“iNature”End往期精选围观王晓红教授团队：绘制单次冷冻囊胚移植成功的女性植入期外周血microRNA动态表达谱，开拓领域创新研究热文维生素B12在细胞重编程与组织再生中发挥关键作用！热文不孕症治疗新方向！又一导致女性不孕的关键因素被发现热文Let-7家族miRNA或为癌症潜在免疫治疗靶点热文一项最新发现或可用于阿尔茨海默病药物开发点击“阅读原文”，了解更多~

临床结果临床失败

2023-02-01

·生物谷

重磅综述！间充质干细胞线粒体转移/传递治疗潜能背后的机制

线粒体是真核细胞能量代谢和细胞活动所必需的，通过氧化磷酸化(OXPHOS)和三磷酸腺苷(ATP)的产生为细胞的生理功能提供所需的能量。此外，适当的线粒体功能是控制细胞应激、细胞内稳态和自噬所必需的。线粒体是真核细胞能量代谢和细胞活动所必需的，通过氧化磷酸化(OXPHOS)和三磷酸腺苷(ATP)的产生为细胞的生理功能提供所需的能量。此外，适当的线粒体功能是控制细胞应激、细胞内稳态和自噬所必需的。因此，适当和足够数量的线粒体的存在对细胞的功能非常重要，如果这些细胞器在细胞中受到破坏，就会导致细胞衰老和失去正常功能。图片来源：https://doi.org/10.1016/j.jconrel.2023.01.059 近日，来自伊朗医科大学的研究者们在Journal of Controlled Release杂志上发表了题为“Mechanisms behind therapeutic potentials of mesenchymal stem cell mitochondria transfer/delivery”的综述性文章，本文综述了间充质干细胞线粒体转移/传递治疗潜能背后的机制。间充质干细胞(MSCs)通过多种机制发挥治疗作用，包括分化能力、产生不同的生长因子、免疫调节因子和细胞外小泡(EV)。除了上述机制外，最近还注意到了MSCs治疗潜力的一个新方面，即通过线粒体转移。 MSCs线粒体转移的各种方法已被用于研究，以受益于它们的治疗潜力。在这些方法中，细胞间接触的MSCs移植后的线粒体转移，EVS介导的线粒体转移，以及MSCs分离线粒体(MSCs-MT)的使用等方法都得到了很好的研究。病理条件可影响细胞处于受损的微环境中，导致细胞线粒体损伤。由于细胞线粒体功能的缺陷导致ATP产量的减少和随后的细胞死亡，恢复线粒体的内容、功能和止血可以影响受损细胞的功能。各种研究表明，MSCs线粒体向其他细胞的转移可以影响细胞的增殖、分化、细胞代谢、炎症反应、细胞衰老、细胞应激和细胞迁移等重要过程。这些细胞属性和行为的变化对于治疗目的非常重要。因此，他们的调查可以对研究者的方向起到重要的作用。间充质干细胞线粒体转移治疗潜能的相关机制图片来源：https://doi.org/10.1016/j.jconrel.2023.01.059 线粒体在基于MSCs的疗法的治疗潜力和特征中扮演着重要的角色。通过上述三种方法中的任何一种将MSCs-mt转移到靶细胞后，靶细胞的各种重要属性，包括增殖、分化、炎症反应、细胞代谢、细胞衰老、细胞应激和细胞迁移能力都会受到影响。在MSCs的许多治疗应用中，破坏线粒体的正常功能或干扰线粒体的转移导致其治疗潜力的取消和降低，这表明线粒体在MSCs的治疗应用中起着举足轻重的作用。考虑到MSCs作为细胞治疗应用的缺陷和局限性，如其成瘤潜能、向损伤部位迁移的缺陷、储存问题、不必要的分化以及注射后在体内多次复制后的细胞衰老等，建议使用MSCs的胞外囊泡和分离的线粒体来治疗各种疾病。目前，在MSCs-MT治疗效果领域的研究大多针对其短期疗效进行了研究，而线粒体能否在长期内起到这样的治疗作用尚不清楚。(生物谷 Bioon.com) 参考文献 Kosar Malekpour et al. Mechanisms behind therapeutic potentials of mesenchymal stem cell mitochondria transfer/delivery. J Control Release. 2023 Jan 27;354:755-769. doi: 10.1016/j.jconrel.2023.01.059.

细胞疗法

100 项与 MSCs therapy(University of Valladolid) 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
骨囊肿	临床2期	西班牙	Red De Terapia Celular	2011-04-01
代谢性骨病	临床2期	西班牙	Red De Terapia Celular	2011-04-01
上颌疾病	临床2期	西班牙	Red De Terapia Celular	2011-04-01