Cellkine: Phase II Study Evaluating Safety and Preliminary Efficacy of Allogeneic, Culture-Expanded Bone Marrow-Derived Mesenchymal Stem Cells in Subjects With Painful Lumbar Facet Joint Arthropathies

The purpose of this research study is to evaluate the safety and effect of bone marrow-derived stem cells for the treatment of low back pain.

开始日期2023-11-03

申办/合作机构

Mayo Clinic

NCT04410731 / Active, not recruiting临床1期

CellKine: Phase I Study Evaluating the Safety and Feasibility of Allogeneic, Culture-Expanded Bone Marrow-Derived Mesenchymal Stem Cells in Subjects With Painful Lumbar Facet Joint Arthropathy

Researchers are conducting this study to learn more about the side effects of bone marrow-derived stem cells when injected into the facet joints for the treatment of painful lumbar facet joint arthropathies.

开始日期2020-04-28

申办/合作机构

Mayo Clinic

EUCTR2017-002092-25-IT / Unknown status临床2/3期

A phase 2/3 prospective, multicentre randomized, double-blind trial, comparing intradiscal allogeneic adult BM-MSC therapy and sham-treated controls in subjects withchronic low back pain due to lumbar degenerative disc disease (DDD) unresponsive toconventional therapy - Efficacy of intradiscal injection of BM-MSC in subjects with chronic LBP due to lumbar DDD unrespons

开始日期2018-06-19

申办/合作机构-

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251

项与 Bone Marrow-Derived Mesenchymal Stem Cells(Mayo Clinic) 相关的文献（医药）

2023-12-13·Clinical and experimental immunology

Effects of mesenchymal stem cells on Treg cells in rats with colitis

Article

作者: Liu, Jing ; Xu, Dan ; Zhao, Qiu ; Cai, Wei ; Shao, Su'E ; Zhang, Heng

Abstract:

The aim was to investigate the therapeutic effect of bone marrow mesenchymal stem cells (BM-MSC) on dextran sulfate sodium (DSS) induced colitis in rats and its effect on regulatory T cells (Treg). A model of DSS-induced colitis was established. BM-MSC was isolated and cultured to observe the efficacy of BM-MSC on colitis, including general vital signs, weight changes, colonic length changes, colonic histopathological changes, and colonic tissue MPO activity. The expression of inflammatory factors (IFN-γ, IL-4, IL-17, TGF-β) in colonic tissues was measured by real-time PCR. The amount of CD4 + CD25 + Treg was detected by flow cytometry. Real-time PCR was used to detect Foxp3+mRNA in CD4 + CD25 + Treg, western to detect Foxp3+protein expression in CD4 + CD25 + Treg, and ELISA was used to detect IL-35 and IL-10 cytokines in CD4 + CD25 + Treg culture supernatant. Results show that intravenous injection of BM-MSC significantly improved the clinical manifestations and histopathological changes in rats with experimental DSS colitis; significantly down-regulated the expression of inflammatory factors IFN-γ, IL-4, and IL-17 and up-regulated the expression of TGF-β in colon tissues; BM-MSC also increased the number of CD4+CD25+Foxp3+Treg and enhanced the function of CD4+CD25+Foxp3+Treg in colon tissues, and up-regulated the expression of IL-35. In conclusion, BM-MSC has a certain therapeutic effect on DSS-induced colitis. It can improve the general signs of colitis rats and reduce intestinal injury and inflammatory response. The immunoregulatory effect of BM-MSC is achieved by enhancing the function of CD4+CD25+Foxp3+Treg and up-regulating the secretion of immunosuppressive inflammatory factors.

2023-12-01·Burns : journal of the International Society for Burn Injuries

Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa

Article

作者: Darban-Sarokhalil, Davood ; Mirshekar, Maryam ; Razavi, Shabnam ; Ohadi, Elnaz ; Nezhad, Majid Mottaghi ; Karimi, Roya ; Masjedian Jazi, Faramarz ; Afkhami, Hamed

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 10⁸ (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

2023-11-01·Equine veterinary journal

Treatment of racehorse superficial digital flexor tendonitis: A comparison of stem cell treatments to controlled exercise rehabilitation in 213 cases

Article

作者: Bennet, Euan D. ; Salz, Rachel O. ; Ahern, Benjamin J. ; Zuffa, Tomas ; Elliott, Christopher R. B.

Abstract:

Background:

Overstrain of the superficial digital flexor tendon (SDFT) is a common Thoroughbred racehorse limb injury requiring treatment.

Objectives:

To determine whether treatment of SDFT lesions in flat Thoroughbred racehorses with autologous bone marrow‐derived mesenchymal stem cells (BM‐MSCs) or allogenic adipose‐derived mesenchymal stem cells (A‐MSCs) is associated with improved likelihood of returning to racing, when compared to racehorses managed with a controlled exercise rehabilitation program (CERP) alone.

Study design:

Retrospective cohort study combining clinical treatment records with race records.

Methods:

A total of 213 Thoroughbred racehorses were identified. All were prescribed the same 12‐month CERP and 66 also received intralesional BM‐MSC and 17 A‐MSC treatment. Follow‐up was a minimum of 2 years after return to full race training. Multivariable logistic regression models were used to investigate associations between the treatments and the likelihood of returning to racing and completing five or more (C5+) races post‐injury.

Results:

Compared to CERP alone, BM‐MSC treatment was associated with increased odds of returning to racing (OR 3.19; 95% CI 1.55–6.81) and C5+ races post‐injury (OR 2.64; 95% CI 1.32–5.33). Older age and increasing lesion length were associated with a reduced likelihood of returning to racing. Male sex and increased number of pre‐injury starts were associated with increased odds of returning to racing. There was no observed increased likelihood of return to racing or C5+ races associated with treatment with A‐MSCs compared to CERP alone.

Main limitations:

Due to the retrospective nature of the study it was not possible to ascertain how strictly the CERP was followed. Due to the novelty of the method, the A‐MSC treatment group included a limited number of horses.

Conclusions:

In the study population, intralesional BM‐MSC treatment was significantly associated with an increased likelihood of returning to racing and C5+ races post‐injury compared to CERP alone. Intralesional A‐MSC showed no significant association between treatment and the two investigated outcomes.

项与 Bone Marrow-Derived Mesenchymal Stem Cells(Mayo Clinic) 相关的新闻（医药）

2023-08-01

·佰傲谷BioValley

间充质干细胞外泌体相关临床试验

间充质基质/干细胞（Mesenchymal stromal/stem cells，MSCs）的旁分泌活性是发挥免疫调节和再生功能的最重要机制之一。在实验模型中细胞外囊泡，特别是外泌体，具有丰富的蛋白质、mRNA和微小RNA。与直径为30-60μm的MSC相比，纳米级外泌体在给药后可以有效转移到特定组织，而不会在肺微血管中聚集，避免了肺栓塞的可能性，正成为一种很有前景的无细胞治疗产品。除了治疗作用外，MSC-Exos还是向靶细胞递送不同分子（包括治疗基因、药物、酶和RNA）的载体。MSC-Exos可以保护这些分子，并通过内吞作用促进其被细胞吸收。此外改变外泌体表面蛋白可获得特异性靶向功能。在动物模型中MSC-Exos可以预防或治疗不同的疾病，包括神经相关疾病、自身免疫性疾病、心脏、肝脏和肾脏疾病。临床研究的MSC-Exos的来源、剂量和给药途径脂肪组织是最常用的来源，已在7项研究中使用，其次是骨髓（5项研究）和脐带（4项研究）。由于MSC-Exos的无免疫原性，研究一般使用同种异体来源的MSC-Exos。临床研究中MSC-Exos的给药途径为静脉输注、吸入或局部给药。临床研究中的给药剂量因给药途径和疾病而异。此外计算MSC-Exos的单位存在差异，一些研究以重量（mg）计算MSC-Exos剂量，一些研究以颗粒数计算MSC-Exos剂量，而另一些研究则注明用于产生MSC-Exos的MSCs的数量。目前对所使用的MSC-Exos的剂量还没有达成共识。分离方法已发表的关于MSC Exos的临床试验主要使用了超速离心法，其次是TFF法。超速离心法是分离MSC-Exos最常用的方法，利用高达1 000 000g的离心力将MSC-Exos从样品中分离出来。切向流超滤装置（TFF）是另一种基于囊泡大小浓缩条件培养基和纯化MSC-Exos的方法。MSC-Exos的表征临床试验的MSC-Exos应符合MISEV2018指南中规定的细胞外囊泡的最低表征标准：（i）至少三种EV蛋白质标记物呈阳性，其中至少一种是跨膜蛋白、脂质结合蛋白或胞质蛋白；（ii）至少一种蛋白标记物呈阴性。物理表征应通过两种不同但互补的技术进行评估，如电子显微镜和单颗粒分析仪。治疗慢性肾脏疾病首次报道使用MSC-Exos治疗慢性肾脏疾病(Chronic kidney disease, CKD)的临床试验是Nassar等人在埃及进行的单中心、随机、安慰剂对照的临床研究，该研究使用脐带血MSC-Exos（UCB-MSC-Exos）。40名年龄在26至44岁之间的CKD III期或IV期患者按1:1的比例随机分为对照组（生理盐水）或UCB MSC Exos组(100 μg/kg)。第一剂是静脉注射，第二剂是动脉注射。在12个月的研究期间，UCB-MSC-Exos组在肾小球滤过率、血清肌酐水平、血尿素和尿白蛋白/尿肌酐比方面取得了显著改善。治疗皮肤色素沉着过度首尔大学一项前瞻性、随机安慰剂对照研究评估了脂肪MSCs的外泌体 (ASC-Exos)对皮肤色素沉着过度的治疗作用。治疗组在化妆品中添加ASC-Exos，每天两次，持续8周。与对照组相比，ASCA-Exos显著降低了黑色素含量。然而改善只持续了2个月，并且随着时间的推移病情复发。ASC-Exos可能诱导神经酰胺或鞘氨醇-1-磷酸的合成，从而影响黑色素细胞中的黑色素生成。ASC-Exos由韩国ExoCoBio Inc公司提供。治疗痤疮疤痕在韩国Oaro皮肤病研究院进行的一项研究中，25名年龄在19至54岁之间的志愿者进行ASC-Exos联合二氧化碳点阵激光(FCL)对面部痤疮瘢痕愈合的效果。患者在激光治疗后两侧脸随机接受1毫升的ASC-Exos或对照凝胶涂抹。结果表明用ASC-Exos治疗侧皮肤毛孔的大小和皮肤表面的粗糙程度较基线有所下降，而对照组没有明显变化。ASC-Exos也是由韩国ExoCoBio Inc公司提供。治疗移植物抗宿主病(GvHD)与造血干细胞移植相关的最严重的并发症之一是急性或慢性移植物抗宿主病(GvHD)。目前GvHD的治疗药物是广泛的全身免疫抑制剂，其应答率低，且机会感染的风险增加。德国杜伊斯堡-埃森大学附属医院的一个病例报告中，给予GvHD患者BM-MSC外泌体，每天1单位(1单位指从4 × 107 BM-MSCs的条件培养基中提取外泌体)，持续2天。然后逐渐增加剂量，每2-3天给药一次，直到达到每天4个单位。患者腹泻量显著减少，皮肤和粘膜GvHD在14 d内得到显著抑制。治疗COVID-19SARS-CoV-2感染引起的急性呼吸窘迫综合征(ARDS)可导致死亡。一项前瞻性开放标签队列临床研究评估了MSC-Exos用于治疗重症COVID-19的安全性和有效性。24名受试者静脉注射来源于BM-MSCs的外泌体(产品名称ExoFlo，美国Direct Biologics公司生产)。给药剂量1-10 × 106 MSCs产生的外泌体/kg。受试者生存率为83%；约71%的患者治愈，13%的患者病情危重但稳定，16%的患者死于与治疗无关的原因。单次给药后受试者的临床状况和氧合情况都有所改善，C反应蛋白降低了77%，铁蛋白降低了43%，D-二聚体降低了42%。上海公共卫生临床中心和中国武汉金银潭医院开展了一项ASC-Exos治疗COVID-19的试验(NCT04276987)。在这项试验中，24名被诊断患有COVID-19的受试者在前5天接受5次2.0×108ASC-Exos/3ml剂量的气雾剂治疗，然后评估28天安全性和有效性。治疗骨关节炎骨关节炎（OA）无法治愈，只能通过药物来减轻疼痛。一项研究中评估了BM-MSC-Exos对各种关节炎的治疗效果。受试者包括33名退伍军人，注射2毫升的单剂量ExoFlo。在输注后6个月，简明疼痛评估量表和Oswestry功能障碍指数评分分别显著提高77%和80%。上肢功能评分和下肢功能评分分别提高了51%和76%。MSC-Exos的临床安全性瑞金医院报道的一项1期临床试验中，Shi等人在24名健康志愿者中检测了雾化异体ASC-Exos的安全性，这些志愿者吸入2× 108至16 × 108的MSC-Exos。所有志愿者一周内未出现不良反应。正在进行的MSC-Exos临床研究脑卒中在一项伊斯法罕医学科学大学举行的1/2期试验中，5名年龄在40至80岁之间的受试者在中风后一个月利用立体定向引导在缺血区域接受一次200mg剂量的用miR-124转染的BM-MSC-Exos。治疗后进行为期12个月的随访，指标包括复发性中风、脑水肿、癫痫发作和缺血性到出血性转化。此外治疗后前12个月使用Rankin量表来衡量改善程度，并通过使用0到6分测量患者的功能障碍程度( NCT03384433)。阿尔茨海默病阿尔茨海默病（AD）是最常见的神经退行性疾病之一。在瑞金医院正在进行的1/2期临床试验(NCT04388982)中，给予9名年龄在50岁及以上的阿尔茨海默病受试者同种异体ASC-Exos。试验的主要目的是测试MSC-Exos治疗AD引起的轻中度痴呆的疗效。三组病人分别通过鼻滴给予5μg、10μg和20μg的ASC Exos，每周两次，持续12周。主要终点包括3个月内的肝肾功能、老年性痴呆评定量表-认知分量表 (ADAS-cog)和ADCS-ADL评分。1型糖尿病(T1DM)在开罗大学Nassar等人为首进行的一项研究中(NCT02138331)，UCB-MSC-Exos在18至60岁，C肽减少50%以上，C肽≥0.8ng/mL，胰岛素≥0.4IU/kg/d的T1DM患者中进行试验。20名患者将接受连续两次的静脉注射。第一剂是从1.22-1.51×106MSCs/kg产生的上清液中提取外泌体。第二剂含有100-1000nm粒径大小的MV，将在第一剂治疗7天后给药。外泌体将通过检测标记物CD63、CD9、Alix、TSG101和HSP70进行表征，而MVs通过膜联蛋白V、Flotillin-2、选择素、整合素和CD40金属蛋白酶来表征。3个月研究期间将测量肝肾功能、HbA1c、葡萄糖耐量、空腹和餐后2小时血糖水平、C肽水平和胰岛素剂量。主要终点是胰岛素剂量的变化和HbA1c水平，并与基线值（入组时候）进行比较。胰腺癌在75%到90%的胰腺癌病例中发现了Kras基因的突变。安德森癌症中心的一项1期研究(NCT03608631)评估携带KrasG12DsiRNA的MSC-Exos（iExosomes)对KrasG12D突变转移性胰腺癌患者的适宜剂量和不良事件。28名18岁或以上的成年患者将接受静脉注射MSC-Exos。受试者将在第1、4和10天接受超过15-20分钟的MSC-Exos静脉给药，每14天重复一次，最多3个疗程。本研究的主要目标是确定患者对MSC-Exos的最大耐受剂量和剂量限制性毒性。黄斑变性由天津眼科医院进行的一项临床试验(NCT03437759)将评估MSC和MSC-Exos治愈难治性黄斑裂孔的安全性和有效性。在这项试验中，44名受1期黄斑裂孔患者接受局部注射50或20μg的MSC-Exos。受试者将接受为期6个月的随访，包括最佳矫正视力检测、眼底镜检查、光学相干层析成像和体检。通过检测术后24周的光学相干层析成像(OCT)测量的裂孔的最小线性直径来评估疗效。治疗COVID-19在萨马拉地区临床医院领导的一项研究中(NCT04491240)将纳入30名年龄在18至65岁之间COVID-19患者。治疗组的患者每天两次吸入3ml含有两种不同类型的0.5–2×1010 MSC-Exos，持续10天。主要终点是出院后30天不良事件。治疗肺部感染在瑞金医院的一项临床研究(NCT04544215)中，同种异体ASC-Exos的气雾剂吸入将用于治疗对碳青霉烯类抗生素耐药的革兰氏阴性杆菌引起的肺部感染。60名年龄在18至75岁之间的受试者将被随机分为低剂量组、高剂量组或安慰剂组。低、高剂量组将分别接受7剂8.0×108ASC-Exos/3ml和 16.0×108ASC-Exos/3ml体积的气雾剂治疗。急性呼吸窘迫综合征(ARDS)ICU收治的患者中大约10%患有ARDS。在针对ARDS的临床试验(NCT04602104)中，瑞金医院研究人员评估吸入同种异体MSC-Exos气雾剂对ARDS的疗效。在这项研究中受试者将被随机分为3组。低、中和稿剂量组分别每天吸入一次2.0×108 、8.0×108和16.0×108 的MSC-Exos的气雾剂，持续一周。多器官功能障碍综合征(MODS)MODS是急性A型主动脉夹层修复术后常见的系统衰竭疾病，是术后死亡的主要原因之一。福建医科大学的一项研究(NCT04356300)将评估MSC-Exos预防和治疗MODS的作用。这项随机研究分为两部分。在第一部分（预防方案）中：15名患者将在升主动脉置换术后立即静脉注射150mg MSC-Exos，每天一次，持续14天，另外15名患者（对照）将接受标准基础护理（SOC）。在第二部分（治疗方案）中15名MODS患者将接受相同剂量的MSC-Exos治疗。6个月内进行器官功能衰竭评估。营养不良大疱性表皮松解症营养不良大疱性表皮松解症(EB)是一种罕见的遗传性水疱病，由VII型胶原蛋白α1(COL7A1)基因突变引起。由Aegle Therapeutics进行的1/2期单药开放标签临床试验中，10例EB患者的病灶上观察BM-MSC-Exos(产品名称:AGLE-102)的安全性和有效性(NCT04173650)。患者将在3个月内接受6剂BM-MSC-Exos治疗。主要终点将是剂量限制毒性。次要终点是伤口大小。慢性GVHD相关干眼症在慢性GvHD(cGVHD)患者中，60-90%的患者发生干眼症。由中山大学中山眼科中心进行该临床研究(NCT04213248)，旨在确定UC-MSC-Exos是否可以缓解cGVHD患者的干眼症状。在这项单药开放标签研究中，在27名年龄在18至70岁之间的受试者身上测试UC-MSC-Exos的疗效。受试者使用人工泪液治疗2周，然后每天4次滴10mg UC-MSC-Exos，持续2周。12周的随访主要终点将是眼表疾病指数评分的变化。次要终点包括泪液分泌、泪膜破裂时间、荧光染色区域、眼睛发红、泪液弯月面和最佳矫正视力。牙周炎在一项正在进行的1期开放标签临床试验(NCT04270006)中，来自埃及贝尼苏夫大学和开罗大学的研究团队计划评估自体ASC-Exos治疗牙周炎的疗效。10名受试者的牙周袋内局部给MSC-Exos，并随访6个月。主要指标将包括牙龈炎症、牙周袋深度、附着水平和骨密度的变化。未来展望全世界越来越多企业对MSC-Exos疗法感兴趣。多项临床前研究报告MSC-Exos疗法在安全性、有效性和功能性等方面优于细胞疗法。需要更多的临床前研究来优化合适的剂量、给药途径和MSC的来源。在临床中使用MSC-Exos也存在一些挑战。例如，MSC-Exos从体内的快速清除会限制长期治疗效果。此外，由于不同的培养条件和细胞传代导致MSC-Exos的异质性是另一个挑战。此外永生化MSC株可能是生成同源MSC-Exos的一种解决方案。另一个挑战是长期保存MSC-Exos的方法。冻干MSC-Exos或通过添加稳定剂（如糖或聚乙二醇）有助于保存外泌体。随着生物工程和细胞操作技术的进步，外泌体未来趋势将是外泌体的工程化。总之MSC-Exos正在成为一种新颖且具有前景的无细胞疗法。参考文献1.Nassar W, El-Ansary M, Sabry D, Mostafa MA, Fayad T, Kotb E, et al. Umbilical cord mesenchymal stem cells derived extracellular vesicles can safely ameliorate the progression of chronic kidney diseases. Biomater Res. 2016;20:21.2.Kwon HH, Yang SH, Lee J, Park BC, Park KY, Jung JY, et al. Combination Treatment with Human Adipose Tissue Stem Cell-derived Exosomes and Fractional CO2 Laser for Acne Scars: A 12-week Prospective, Double-blind, Randomized, Split-face Study. Acta dermato-venereologica. 2020;100(18):adv00310-adv.3.Kordelas L, Rebmann V, Ludwig AK, Radtke S, Ruesing J, Doeppner TR, et al. MSC-derived exosomes: a novel tool to treat therapy-refractory graft-versus-host disease. Leukemia. 2014;28(4):970–3.4.Sengupta V, Sengupta S, Lazo A, Woods P, Nolan A, Bremer N. Exosomes Derived from Bone Marrow Mesenchymal Stem Cells as Treatment for Severe COVID-19. Stem Cells Dev. 2020;29(12):747–54.5.Dordevic M. IRB approved pilot safety study of an extracellular vesicle isolate product evaluating the treatment of osteoarthritis in combat-related injuries. 2020;1:11.本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀‍‍ ·········点亮在看，传递信息♥

临床3期信使RNA临床1期临床2期

100 项与 Bone Marrow-Derived Mesenchymal Stem Cells(Mayo Clinic) 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
腰椎关节突关节病	临床2期	美国	Mayo Clinic	2023-11-03
腰痛	临床2期	美国	Mayo Clinic	2023-11-03

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


P120 (EBMT2020)	N/A	类固醇难治性移植物抗宿主病	18	WJ-MSC	艱醖製窪築壓廠繭築顧(廠淵艱網醖衊衊築鬱選) = 淵衊餘廠憲遞範構鬱獵鑰選構獵壓鬱蓋襯構憲 (願積憲構齋蓋壓獵網顧 )	积极	2020-08-29
				BM-MSC	艱醖製窪築壓廠繭築顧(廠淵艱網醖衊衊築鬱選) = 艱艱鏇簾築鹹築醖窪壓鑰選構獵壓鬱蓋襯構憲 (願積憲構齋蓋壓獵網顧 )