Institute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, 27/10, Lomonosovskiy av., 119192 Moscow, Russia.
Faculty of Medicine, Lomonosov Moscow State University, 27/1, Lomonosovskiy av., 119192 Moscow, Russia.
Int J Mol Sci. 2023 May 27;24(11):9379. doi: 10.3390/ijms24119379.
Adult stem cells maintaining tissue homeostasis and regeneration are tightly regulated by their specific microenvironments or stem cell niches. The dysfunction of niche components may alter the activity of stem cells and ultimately lead to intractable chronic or acute disorders. To overcome this dysfunction, niche-targeting regenerative medicine treatments such as gene, cell, and tissue therapy are actively investigated. Here, multipotent mesenchymal stromal cells (MSCs), and particularly their secretomes, are of high interest due to their potency to recover and reactivate damaged or lost stem cell niches. However, a workflow for the development of MSC secretome-based products is not fully covered by regulatory authorities, and and this issue significantly complicates their clinical translation and has possibly been expressed in a huge number of failed clinical trials. One of the most critical issues in this regard relates to the development of potency assays. In this review, guidelines for biologicals and cell therapies are considered to be applied for the development of potency assays for the MSC secretome-based products that aim for tissue regeneration. Specific attention is paid to their possible effects on stem cell niches and to a spermatogonial stem cell niche in particular.
成体干细胞通过其特定的微环境或干细胞龛来维持组织内稳态和再生，其受到严格的调控。龛位成分的功能障碍可能会改变干细胞的活性，最终导致难治性慢性或急性疾病。为了克服这种功能障碍，人们积极研究龛位靶向的再生医学治疗方法，如基因、细胞和组织治疗。在这里，多能间充质基质细胞（MSCs），特别是它们的分泌组，由于其恢复和重新激活受损或丢失的干细胞龛位的能力而受到高度关注。然而，监管机构并没有完全涵盖基于 MSC 分泌组的产品的开发工作流程，这个问题极大地复杂化了它们的临床转化，并且可能在大量失败的临床试验中表现出来。在这方面，最关键的问题之一与效力检测的开发有关。在这篇综述中，考虑了生物制品和细胞治疗的指南，以应用于旨在进行组织再生的基于 MSC 分泌组的产品的效力检测的开发。特别关注它们对干细胞龛位的可能影响，特别是对精原干细胞龛位的影响。
