Monti Manuela, Imberti Barbara, Bianchi Niccolò, Pezzotta Anna, Morigi Marina, Del Fante Claudia, Redi Carlo Alberto, Perotti Cesare
1 Research Center for Regenerative Medicine, Biotechnologies Research Laboratories, Fondazione IRCCS Policlinico San Matteo , Pavia, Italy .
2 Cell Biology and Regenerative Medicine Laboratory, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri," Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso , Bergamo, Italy .
Stem Cells Dev. 2017 Sep 1;26(17):1258-1269. doi: 10.1089/scd.2017.0012. Epub 2017 Jun 4.
Very small embryonic-like cells (VSELs) are a population of very rare pluripotent stem cells isolated in adult murine bone marrow and many other tissues and organs, including umbilical cord blood (UCB). VSEL existence is still not universally accepted by the scientific community, so for this purpose, we sought to investigate whether presumptive VSELs (pVSELs) could be isolated from human UCB with an improved protocol based on the isolation of enriched progenitor cells by depletion of nonprogenitor cells with magnetic separation. Progenitor cells, likely including VSELs, cultured with retinoic acid were able to form dense colonies and cystic embryoid bodies and to differentiate toward the ecto-meso-endoderm lineages as shown by the positivity to specific markers. VSEL differentiative potential toward mesodermal lineage was further demonstrated in vitro upon exposure to an established inductive protocol, which induced the acquisition of renal progenitor cell phenotype. VSEL-derived renal progenitors showed regenerative potential in a cisplatin model of acute kidney injury by restoring renal function and tubular structure through induction of proliferation of endogenous renal cells. The data presented here foster the great debate that surrounds VSELs and, more in general, the existence of cells endowed with pluripotent features in adult tissues. In fact, the possibility to find and isolate subpopulations of cells that fully fit all the criteria utilized to define pluripotency remains, nowadays, almost unproven. Thus, efforts to better characterize the phenotype of these intriguing cells are crucial to understand their possible applications for regenerative and precision medicine purposes.
极小型胚胎样细胞（VSELs）是在成年小鼠骨髓以及包括脐带血（UCB）在内的许多其他组织和器官中分离出的一群极为罕见的多能干细胞。科学界对VSELs的存在尚未普遍接受，因此，为了探究这一问题，我们试图采用一种改进方案，通过磁珠分选去除非祖细胞来分离富集祖细胞，从而从人脐带血中分离出假定的VSELs（pVSELs）。用视黄酸培养的祖细胞（可能包括VSELs）能够形成致密集落和囊性胚状体，并向外-中-内胚层谱系分化，这通过对特定标志物呈阳性得以证明。在体外，当暴露于既定的诱导方案时，VSELs向中胚层谱系的分化潜能进一步得到证实，该方案诱导了肾祖细胞表型的获得。在顺铂诱导的急性肾损伤模型中，VSEL来源的肾祖细胞通过诱导内源性肾细胞增殖恢复肾功能和肾小管结构，显示出再生潜能。本文提供的数据引发了围绕VSELs以及更广泛而言成年组织中具有多能特性细胞存在与否的激烈争论。事实上，如今几乎没有证据能够证明找到并分离出完全符合用于定义多能性所有标准的细胞亚群的可能性。因此，努力更好地表征这些有趣细胞的表型对于理解它们在再生医学和精准医学中的潜在应用至关重要。
