Institute for Regenerative Medicine, Medical research and education center, Lomonosov Moscow State University, Moscow 119192, Russia.
Faculty of Medicine, Lomonosov Moscow State University, Moscow 119192, Russia.
Int J Mol Sci. 2019 Feb 14;20(4):823. doi: 10.3390/ijms20040823.
Regeneration is a fundamental process attributed to the functions of adult stem cells. In the last decades, delivery of suspended adult stem cells is widely adopted in regenerative medicine as a leading means of cell therapy. However, adult stem cells cannot complete the task of human body regeneration effectively by themselves as far as they need a receptive microenvironment (the niche) to engraft and perform properly. Understanding the mechanisms underlying mammalian regeneration leads us to an assumption that improved outcomes of cell therapy require a specific microenvironment that is generated in damaged areas prior to stem cell delivery. To a certain extent, it may be achieved by the delivery of mesenchymal stromal cells (MSCs), not in dispersed form, but rather in self-organized cell sheets (CS) ⁻ tissue-like structures comprised of viable cells and microenvironment components: extracellular matrix and soluble factors deposited in the matrix. In this review, we highlight the potential role of MSCs as regeneration organizers and speculate that this function emerges in CS. This concept shifts our understanding of the therapeutic mechanism underlying a widely known CS-based delivery method for regenerative medicine.
再生是一种归因于成体干细胞功能的基本过程。在过去的几十年中，悬浮的成体干细胞的递送已被广泛应用于再生医学中，作为细胞治疗的主要手段。然而，成体干细胞本身并不能有效地完成人体再生的任务，因为它们需要一个接受的微环境（生态位）才能适当植入和发挥作用。对哺乳动物再生机制的理解使我们假设，细胞治疗的改善结果需要在干细胞递送之前在受损区域产生特定的微环境。在某种程度上，这可以通过间充质基质细胞（MSC）的递送来实现，不是以分散的形式，而是以自组织的细胞片（CS） ⁻ 由有活力的细胞和微环境成分组成的组织样结构：细胞外基质和沉积在基质中的可溶性因子。在这篇综述中，我们强调了 MSC 作为再生组织者的潜在作用，并推测这种功能出现在 CS 中。这一概念改变了我们对再生医学中基于 CS 的广泛应用的治疗机制的理解。
