间充质干细胞/基质细胞(MSC)分布在各种组织中,并且由于其易于收获而在临床应用中用作移植细胞的来源。虽然MSCs表达多种细胞表面抗原,单细胞分析显示,取决于原始组织和供体条件,高度异质的细胞群。包括年龄和个体差异。这种异质性导致它们的功能差异,如多能性和免疫调节作用,使得有效治疗目标疾病具有挑战性。MSC的治疗功效是有争议的,并且取决于植入部位。因此,没有确定的MSCs移植配方(包括疾病的类型,原产地类型,细胞培养方法,移植细胞的形式,和交货地点)。我们最近的临床前研究在炎症性肠病(IBD)小鼠模型中确定了合适的MSCs及其合适的移植途径。已经证明MSC的三维(3D)培养物增强其性质并维持在损伤部位的植入。在本说明中,我们探索MSC移植治疗IBDs的方法,尤其是克罗恩病,来自过去十年发表的临床试验。鉴于MSCs在3D培养中的功能变化,我们还研究了使用MSCs3D构建体的临床试验,并探索了可能受益于该方法的合适疾病.此外,我们讨论了前瞻性分离MSCs在个体差异方面的优势.本说明强调了定义MSC移植方法的必要性,包括个体差异,文化时期,和移植途径。
Mesenchymal stem/stromal cells (MSCs) are distributed in various tissues and are used in clinical applications as a source of transplanted cells because of their easy harvestability. Although MSCs express numerous cell-surface antigens, single-cell analyses have revealed a highly heterogeneous cell population depending on the original tissue and donor conditions, including age and interindividual differences. This heterogeneity leads to differences in their functions, such as multipotency and immunomodulatory effects, making it challenging to effectively treat targeted diseases. The therapeutic efficacy of MSCs is controversial and depends on the implantation site. Thus, there is no established recipe for the transplantation of MSCs (including the type of disease, type of origin, method of cell culture, form of transplanted cells, and site of delivery). Our recent preclinical study identified appropriate MSCs and their suitable transplantation routes in a mouse model of inflammatory bowel disease (IBD). Three-dimensional (3D) cultures of MSCs have been demonstrated to enhance their properties and sustain engraftment at the lesion site. In this note, we explore the methods of MSC transplantation for treating IBDs, especially Crohn\'s disease, from clinical trials published over the past decade. Given the functional changes in MSCs in 3D culture, we also investigate the clinical trials using 3D constructs of MSCs and explore suitable diseases that might benefit from this approach. Furthermore, we discuss the advantages of the prospective isolation of MSCs in terms of interindividual variability. This note highlights the need to define the method of MSC transplantation, including interindividual variability, the culture period, and the transplantation route.