denovoMATRIX GmbH, Dresden, Germany.
Universitätskrankenhaus Carl Gustav Carus der Technischen Universität Dresden, Dresden, Germany.
Cytotherapy. 2022 Oct;24(10):1049-1059. doi: 10.1016/j.jcyt.2022.06.003. Epub 2022 Aug 2.
Mesenchymal stromal cells (MSCs) are one of the most frequently used cell types in regenerative medicine and cell therapy. Generating sufficient cell numbers for MSC-based therapies is constrained by (i) their low abundance in tissues of origin, which imposes the need for significant ex vivo cell expansion; (ii) donor-specific characteristics, including MSC frequency/quality, that decline with disease state and increasing age; and (iii) cellular senescence, which is promoted by extensive cell expansion and results in decreased therapeutic functionality. The final yield of a manufacturing process is therefore primarily determined by the applied isolation procedure and its efficiency in isolating therapeutically active cells from donor tissue. To date, MSCs are predominantly isolated using media supplemented with either serum or its derivatives, which poses safety and consistency issues.
To overcome these limitations while enabling robust MSC production with constant high yield and quality, the authors developed a chemically defined biomimetic surface coating called isoMATRIX (denovoMATRIX GmbH, Dresden, Germany) and tested its performance during isolation of MSCs.
The isoMATRIX facilitates the isolation of significantly higher numbers of MSCs in xenogeneic (xeno)/serum-free and chemically defined conditions. The isolated cells display a smaller cell size and higher proliferation rate than those derived from a serum-containing isolation procedure and a strong immunomodulatory capacity. The high proliferation rates can be maintained up to 5 passages after isolation and cells even benefit from a switch towards a proliferation-specific MSC matrix (myMATRIX MSC) (denovoMATRIX GmbH, Dresden, Germany).
In sum, isoMATRIX promotes enhanced xeno/serum-free and chemically defined isolation of human MSCs and supports consistent and reliable cell performance for improved stem cell-based therapies.
间充质基质细胞(MSCs)是再生医学和细胞治疗中最常使用的细胞类型之一。基于 MSC 的治疗需要足够数量的细胞,这受到以下因素的限制:(i)它们在原始组织中的丰度低,这需要大量的体外细胞扩增;(ii)供体特异性特征,包括 MSC 的频率/质量,随着疾病状态和年龄的增加而下降;(iii)细胞衰老,这是由广泛的细胞扩增促进的,导致治疗功能降低。因此,制造过程的最终产量主要取决于应用的分离程序及其从供体组织中分离治疗活性细胞的效率。迄今为止,MSC 主要使用补充有血清或其衍生物的培养基进行分离,这存在安全性和一致性问题。
为了克服这些限制,同时实现稳健的 MSC 生产,具有恒定的高产率和高质量,作者开发了一种称为 isoMATRIX 的化学定义仿生表面涂层(denovoMATRIX GmbH,德累斯顿,德国),并在 MSC 分离过程中测试了其性能。
isoMATRIX 促进了在异种(xeno)/无血清和化学定义条件下分离出显著更多数量的 MSC。与来源于含血清分离程序的细胞相比,分离出的细胞具有更小的细胞大小和更高的增殖率,以及更强的免疫调节能力。高增殖率可在分离后维持 5 代以上,细胞甚至受益于向增殖特异性 MSC 基质(myMATRIX MSC)(denovoMATRIX GmbH,德累斯顿,德国)的转变。
总之,isoMATRIX 促进了增强的异种/无血清和化学定义的人 MSC 分离,并支持一致和可靠的细胞性能,以改善基于干细胞的治疗。