Institut National de la Recherche et Santé Médicale U, Université Paris XI, Kremlin Bicêtre, France.
Hum Gene Ther. 2010 Sep;21(9):1045-56. doi: 10.1089/hum.2010.115.
This review describes the historical emergence of the concept of bone marrow mesenchymal stem cells (MSCs), summarizing data on Wolf and Trentin's hematopoietic inductive microenvironment; Dexter's hematopoiesis-supportive stromal cells; Friedenstein's osteogenic cells; and Pittenger's trilineal osteoblastic, chondrocytic, and adipocytic precursors; to finally introduce the specific bone marrow mesenchymal stem cells with differentiation potential to four lineages (mesenchymal and vascular smooth muscle lineages), and stromal and immunomodulatory capacities. Two points are the object of detailed discussion. The first point envisions the stem cell attributes (multipotentiality, self-renewal, tissue regeneration, population heterogeneity, plasticity, and lineage priming) compared with that of the paradigmatic hematopoietic stem cell. In the second point, we discuss the possible existence of bone marrow cells with greater differentiation potential, eventually pluripotential cells. The latter point raises the issues of cell fusion, reprogramming, or selection under nonstandardized conditions of rare populations of neuroectodermal origin, or of cells that had undergone mesenchymal-to-epithelial transition. In the last section, we review data on MSC senescence and possible malignant transformation secondary to extensive culture, gene transfer of telomerase, or mutations such as leading to Ewing's sarcoma. The set of data leads to the conclusion that bone marrow MSCs constitute a specific adult tissue stem cell population. The multiple characteristics of this stem cell type account for the versatility of the mechanisms of injured tissue repair. Although MSC administration may be extremely useful in a number of clinical applications, their transplantation is not without risks that must not be overlooked when developing cell therapy protocols.
这篇综述描述了骨髓间充质干细胞（MSCs）概念的历史起源，总结了 Wolf 和 Trentin 的造血诱导微环境；Dexter 的造血支持基质细胞；Friedenstein 的成骨细胞；以及 Pittenger 的三系成骨细胞、软骨细胞和脂肪细胞前体细胞；最后介绍了具有向四个谱系（间充质和血管平滑肌谱系）以及基质和免疫调节能力分化潜能的特定骨髓间充质干细胞。有两点是详细讨论的对象。第一点设想了干细胞属性（多能性、自我更新、组织再生、群体异质性、可塑性和谱系启动）与典型造血干细胞的比较。第二点，我们讨论了骨髓中可能存在具有更大分化潜能的细胞，最终是多能细胞。后一点提出了细胞融合、重编程或在非标准条件下选择神经外胚层起源的稀有群体细胞，或经历间充质-上皮转化的细胞的问题。在最后一节中，我们回顾了关于 MSC 衰老和可能恶性转化的的数据，这些数据是由于广泛培养、端粒酶的基因转移或导致尤文肉瘤的突变等原因引起的。这组数据得出的结论是，骨髓间充质干细胞构成了一种特定的成人组织干细胞群体。这种干细胞类型的多种特征解释了损伤组织修复机制的多功能性。尽管 MSC 给药在许多临床应用中可能非常有用，但在开发细胞治疗方案时，不能忽视其移植存在的风险。
