Allogeneic bone marrow derived clonal mesenchymal stromal cells in refractory rheumatoid arthritis: a pilot study.

IF 2.4 4区医学 Q4 CELL & TISSUE ENGINEERING

Regenerative medicine Pub Date : 2024-12-01 Epub Date: 2024-12-23 DOI:10.1080/17460751.2024.2443352

Ahmadreza Jamshidi, Alireza Beheshti Maal, Majid Alikhani, Hoda Madani, Bahareh Sadri, Maryam Moghaddassi, Ahmad Salimzadeh, Mahtab Ahmadipour, Mohammad Amin Shahrbaf, Ensiyeh Hajizadeh-Saffar, Mohamadreza Baghaban Eslaminejad, Seyedeh-Nafiseh Hassani, Leila Taghiyar, Fatemeh Abbasi, Hossein Baharvand, Massoud Vosough

{"title":"Allogeneic bone marrow derived clonal mesenchymal stromal cells in refractory rheumatoid arthritis: a pilot study.","authors":"Ahmadreza Jamshidi, Alireza Beheshti Maal, Majid Alikhani, Hoda Madani, Bahareh Sadri, Maryam Moghaddassi, Ahmad Salimzadeh, Mahtab Ahmadipour, Mohammad Amin Shahrbaf, Ensiyeh Hajizadeh-Saffar, Mohamadreza Baghaban Eslaminejad, Seyedeh-Nafiseh Hassani, Leila Taghiyar, Fatemeh Abbasi, Hossein Baharvand, Massoud Vosough","doi":"10.1080/17460751.2024.2443352","DOIUrl":null,"url":null,"abstract":"Aims: This phase I trial assessed the safety and potential efficacy of monthly 3 dose intravenous infusion of allogeneic bone marrow-derived clonal mesenchymal stromal cells (BM-cMSCs) in refractory rheumatoid arthritis (RA) patients over 24 weeks.Patients & methods: Six patients with refractory RA received BM-cMSC infusions at one-month intervals over a 24-week period. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Clinical efficacy was assessed using the Visual Analog Scale (VAS), Simple and Clinical Disease Activity Indices (SDAI/CDAI), Health Assessment Questionnaire (HAQ), and American College of Rheumatology (ACR) response criteria. Serological makers including: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IL-10, IL-17, TNF-α, and Treg/Th17 ratios were measured.Results: BM-cMSC infusions were well-tolerated, with no SAEs reported. VAS scores improved in three patients, with two achieving sustained pain relief and quality-of-life enhancement. Four patients met ACR20 at week 16, while SDAI and CDAI scores indicated disease activity reduction in three patients. Anti-CCP and RF levels showed variable responses, with some increases not consistently correlating with clinical outcomes. Serological biomarkers showed mixed results; IL-10 increased in five patients, while pro-inflammatory markers TNF-α and IL-17 decreased in the same individuals.Conclusions: BM-cMSC therapy demonstrated a favorable safety profile and potential efficacy in managing refractory RA. While preliminary results are promising, further studies with larger cohorts and long-term follow-up are needed to validate these findings and optimize therapeutic strategies.Clinical trial registration: IRCT20080728001031N29.","PeriodicalId":21043,"journal":{"name":"Regenerative medicine","volume":" ","pages":"599-609"},"PeriodicalIF":2.4000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Regenerative medicine","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1080/17460751.2024.2443352","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/23 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"CELL & TISSUE ENGINEERING","Score":null,"Total":0}

引用次数: 0

Abstract

Aims: This phase I trial assessed the safety and potential efficacy of monthly 3 dose intravenous infusion of allogeneic bone marrow-derived clonal mesenchymal stromal cells (BM-cMSCs) in refractory rheumatoid arthritis (RA) patients over 24 weeks.

Patients & methods: Six patients with refractory RA received BM-cMSC infusions at one-month intervals over a 24-week period. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Clinical efficacy was assessed using the Visual Analog Scale (VAS), Simple and Clinical Disease Activity Indices (SDAI/CDAI), Health Assessment Questionnaire (HAQ), and American College of Rheumatology (ACR) response criteria. Serological makers including: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), IL-10, IL-17, TNF-α, and Treg/Th17 ratios were measured.

Results: BM-cMSC infusions were well-tolerated, with no SAEs reported. VAS scores improved in three patients, with two achieving sustained pain relief and quality-of-life enhancement. Four patients met ACR20 at week 16, while SDAI and CDAI scores indicated disease activity reduction in three patients. Anti-CCP and RF levels showed variable responses, with some increases not consistently correlating with clinical outcomes. Serological biomarkers showed mixed results; IL-10 increased in five patients, while pro-inflammatory markers TNF-α and IL-17 decreased in the same individuals.

Conclusions: BM-cMSC therapy demonstrated a favorable safety profile and potential efficacy in managing refractory RA. While preliminary results are promising, further studies with larger cohorts and long-term follow-up are needed to validate these findings and optimize therapeutic strategies.

Clinical trial registration: IRCT20080728001031N29.

查看原文本刊更多论文

难治性类风湿关节炎中的同种异体骨髓衍生克隆间充质基质细胞：一项初步研究。

目的：这项I期试验评估了每月3次静脉输注同种异体骨髓源性克隆间充质间质细胞（bmp - cmscs）治疗难治性类风湿关节炎（RA）患者超过24周的安全性和潜在疗效。患者和方法：6例难治性RA患者在24周内每隔1个月接受BM-cMSC输注。安全性结局包括不良事件（ae）和严重不良事件（sae）。采用视觉模拟量表（VAS）、简单和临床疾病活动指数（SDAI/CDAI）、健康评估问卷（HAQ）和美国风湿病学会（ACR）反应标准评估临床疗效。血清学指标包括：红细胞沉降率（ESR）、c反应蛋白（CRP）、IL-10、IL-17、TNF-α和Treg/Th17比值。结果：BM-cMSC输注耐受性良好，未见不良反应报告。3名患者的VAS评分得到改善，2名患者实现了持续的疼痛缓解和生活质量的提高。4名患者在第16周达到ACR20，而SDAI和CDAI评分表明3名患者的疾病活动性降低。抗ccp和RF水平表现出不同的反应，一些升高与临床结果并不一致。血清学生物标志物显示混合结果；5例患者IL-10升高，而促炎标志物TNF-α和IL-17降低。结论：BM-cMSC治疗在治疗难治性RA方面具有良好的安全性和潜在疗效。虽然初步结果很有希望，但需要更大的队列和长期随访的进一步研究来验证这些发现并优化治疗策略。临床试验注册：IRCT20080728001031N29。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Regenerative medicine 医学-工程：生物医学

CiteScore

4.20

自引率

3.70%

发文量

审稿时长

6-12 weeks

期刊介绍： Regenerative medicine replaces or regenerates human cells, tissue or organs, to restore or establish normal function*. Since 2006, Regenerative Medicine has been at the forefront of publishing the very best papers and reviews covering the entire regenerative medicine sector. The journal focusses on the entire spectrum of approaches to regenerative medicine, including small molecule drugs, biologics, biomaterials and tissue engineering, and cell and gene therapies – it’s all about regeneration and not a specific platform technology. The journal’s scope encompasses all aspects of the sector ranging from discovery research, through to clinical development, through to commercialization. Regenerative Medicine uniquely supports this important area of biomedical science and healthcare by providing a peer-reviewed journal totally committed to publishing the very best regenerative medicine research, clinical translation and commercialization. Regenerative Medicine provides a specialist forum to address the important challenges and advances in regenerative medicine, delivering this essential information in concise, clear and attractive article formats – vital to a rapidly growing, multidisciplinary and increasingly time-constrained community. Despite substantial developments in our knowledge and understanding of regeneration, the field is still in its infancy. However, progress is accelerating. The next few decades will see the discovery and development of transformative therapies for patients, and in some cases, even cures. Regenerative Medicine will continue to provide a critical overview of these advances as they progress, undergo clinical trials, and eventually become mainstream medicine.