摘要
间充质干/基质细胞(mesenchymal stem/stromal cells,MSCs)因具有多种生物学特性,成为基础和临床研究的热点,其免疫调节和再生特性被广泛应用于临床细胞治疗与研究。经过十多年的进展,应用MSCs的临床试验数量迅猛增长,目前已经有1000多项临床试验已经完成或正在开展,但要将MSCs开发成安全、有效、质量可控以及工艺稳定的活细胞药物同样面临挑战,需要进行临床前成药性研究评价;同时,需要完成临床前的药理药效研究、药代动力学研究及非临床安全性研究等。目前国际上已有十多个MSCs药物获批上市,2025年1月,中国国家药品监督管理局通过优先审评审批程序附条件批准了脐带来源的MSCs药物上市,标志着中国已经进入了MSCs药物商业化发展阶段。尽管取得了一定的成果,但获批的药品数量和大量临床研究数量不成比例,重要的原因是目前对MSCs的作用机制不完全明确,导致临床试验的患者分层不精准,多个临床试验结果不及预期。在未来,需要进行更多的机制探讨、PK-PD研究、规模化制备技术开发等研究工作。随着新知识和方法的出现,MSCs细胞外囊泡、基因修饰的MSCs、细胞+生物材料的复合产品的开发也引人注目。另外,与临床疗效相关的生物标志物、联合用药等方面的探索研究也将为间充质干/基质细胞药物更早造福广大患者提供助力。
MSCs,with their diverse biological properties,have become a focal point in both basic andclinical research.Their immune-regulating and regenerative capabilities are widely utilized in clinical cell therapiesand studies.Over the past decade,clinical trials involving MSCs have surged dramatically,with over 1000 trialseither completed or ongoing.However,developing MSCs into safe,effective,quality-controlled,and process-stableliving cell therapies remains challenging,necessitating preclinical drugability evaluations.Concurrently,preclinical pharmacological studies,pharmacokinetic research,and non-clinical safety assessments must be conducted.Todate,more than a dozen MSC-based drugs have been approved globally.In January 2025,NMPA(National MedicalProducts Administration)conditionally approved umbilical cord-derived MSCs through expedited review and approval procedures,marking the country’s entry into the commercialization phase of MSC therapies.Despite theseachievements,the number of approved drugs remains disproportionately low compared with the volume of clinicaltrials.This imbalance primarily stems from incomplete understanding of MSC mechanisms,leading to imprecisepatient stratification in trials and suboptimal outcomes across multiple studies.In the future,more research effortsare required in areas such as mechanism exploration,PK-PD studies,and large-scale preparation technology development.With emerging knowledge and methodologies,the development of MSC extracellular vesicles,geneticallymodified MSCs,and composite products combining cells with biomaterials has gained significant attention.Furthermore,exploratory studies on clinical efficacy-related biomarkers and combination therapies are advancing thedevelopment of mesenchymal stem/stromal cell-based drugs,paving the way for their broader application in treating patients.
作者
龚伟
韩之波
GONG Wei;HAN Zhibo(National Engineering Research Center of Cell Products,AmCellGene Co.,Ltd.,Tianjin 300457,China;Institute of Hematology&BloodDiseases Hospital,Chinese Academy of Medical Sciences&Peking Union Medical College,Tianjin 300020,China)
出处
《中国细胞生物学学报》
2026年第1期66-77,共12页
Chinese Journal of Cell Biology
关键词
间充质干/基质细胞
细胞药物
临床试验
mesenchymal stem/stromal cell
cell-based therapeutics
clinical trials
