Human dermal mesenchymal stromal cells (MSCs) expressing the ATP-binding cassette (ABC) efflux transporter ABCB5 represent an easily accessible MSC population that, based on preclinical and first-in-human data, holds significant promise to treat a broad spectrum of conditions associated not only with skin-related but also systemic inflammatory and/or degenerative processes. We have developed a validated Good Manufacturing Practice-compliant expansion and manufacturing process by which ABCB5+ MSCs derived from surgical discard skin tissues are processed to an advanced-therapy medicinal product (ATMP) for clinical use. Enrichment for ABCB5+ MSCs is achieved in a three-step process involving plastic adherence selection, expansion in a highly efficient MSC-selecting medium, and immunomagnetic isolation of the ABCB5+ cells from the mixed culture. Product Quality Review data covering 324 cell expansions, 728 ABCB5+ MSC isolations, 66 ABCB5+ MSC batches, and 85 final drug products reveal high process robustness and reproducible, reliable quality of the manufactured cell therapy product. We have successfully established an expansion and manufacturing process that enables the generation of homogenous ABCB5+ MSC populations of proven biological activity manufactured as a standardized, donor-independent, highly pure, and highly functional off-the-shelf available ATMP, which is currently tested in multiple clinical trials.

中文翻译：

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供人使用的同种异体离体扩增 ABCB5+ 间充质基质细胞的工艺数据：现成的 GMP 制造的不依赖供体的 ATMP

表达 ATP 结合盒 (ABC) 外排转运蛋白 ABCB5 的人真皮间充质基质细胞 (MSC) 代表了一种易于获取的 MSC 群体，根据临床前和首次人体数据，该细胞有望治疗广泛的相关疾病不仅与皮肤有关，而且与全身炎症和/或退化过程有关。我们开发了一种经过验证的符合良好生产规范的扩展和制造工艺，通过该工艺将来自手术废弃皮肤组织的 ABCB5+ MSC 加工成用于临床的先进治疗药物产品 (ATMP)。ABCB5+ MSCs 的富集是通过一个三步过程实现的，包括塑料粘附选择、在高效 MSC 选择培养基中扩增以及从混合培养物中免疫磁性分离 ABCB5+ 细胞。涵盖 324 次细胞扩增、728 次 ABCB5+ MSC 分离、66 次 ABCB5+ MSC 批次和 85 种最终药物产品的产品质量审查数据表明，制造的细胞治疗产品具有高度的工艺稳健性和可重现性、可靠的质量。我们已经成功地建立了一个扩展和制造过程，能够生成同质的 ABCB5+ MSC 群体，这些群体具有经过验证的生物活性，被制造为标准化、独立于供体、高纯度和高功能的现成可用 ATMP，目前正在测试多项临床试验。