Institut National de la Santé et Recherche Médicale U972, Hôpital de Bicêtre, Le Kremlin Bicêtre, France.
Stem Cell Rev Rep. 2011 Mar;7(1):32-42. doi: 10.1007/s12015-010-9125-6.
Genostem (acronym for "Adult mesenchymal stem cells engineering for connective tissue disorders. From the bench to the bed side") has been an European consortium of 30 teams working together on human bone marrow Mesenchymal Stem Cell (MSC) biological properties and repair capacity. Part of Genostem activity has been dedicated to the study of basic issues on undifferentiated MSCs properties and on signalling pathways leading to the differentiation into 3 of the connective tissue lineages, osteoblastic, chondrocytic and tenocytic. We have evidenced that native bone marrow MSCs and stromal cells, forming the niche of hematopoietic stem cells, were the same cellular entity located abluminally from marrow sinus endothelial cells. We have also shown that culture-amplified, clonogenic and highly-proliferative MSCs were bona fide stem cells, sharing with other stem cell types the major attributes of self-renewal and of multipotential priming to the lineages to which they can differentiate (osteoblasts, chondrocytes, adipocytes and vascular smooth muscle cells/pericytes). Extensive transcription profiling and in vitro and in vivo assays were applied to identify genes involved in differentiation. Thus we have described novel factors implicated in osteogenesis (FHL2, ITGA5, Fgf18), chondrogenesis (FOXO1A) and tenogenesis (Smad8). Another part of Genostem activity has been devoted to studies of the repair capacity of MSCs in animal models, a prerequisite for future clinical trials. We have developed novel scaffolds (chitosan, pharmacologically active microcarriers) useful for the repair of both bone and cartilage. Finally and most importantly, we have shown that locally implanted MSCs effectively repair bone, cartilage and tendon.
Genostem（成人间充质干细胞治疗结缔组织疾病的缩写，从实验室到病床）是一个由 30 个团队组成的欧洲联盟，致力于研究人类骨髓间充质干细胞（MSC）的生物学特性和修复能力。Genostem 的部分活动致力于研究未分化 MSC 特性和分化为 3 种结缔组织谱系（成骨细胞、软骨细胞和成纤维细胞）的信号通路的基本问题。我们已经证明，位于骨髓窦内皮细胞腔侧的骨髓固有MSC 和基质细胞是造血干细胞龛的相同细胞实体。我们还表明，经培养扩增、克隆形成和高度增殖的 MSC 是真正的干细胞，它们与其他干细胞类型一样，具有自我更新和多能性启动的主要特征，可分化为它们可以分化的谱系（成骨细胞、软骨细胞、脂肪细胞和血管平滑肌细胞/周细胞）。我们应用广泛的转录谱分析以及体外和体内实验来鉴定参与分化的基因。因此，我们描述了一些新的参与成骨作用的因子（FHL2、ITGA5、Fgf18）、软骨生成（FOXO1A）和成纤维细胞生成（Smad8）。Genostem 活动的另一部分致力于研究 MSC 在动物模型中的修复能力，这是未来临床试验的前提。我们开发了用于修复骨和软骨的新型支架（壳聚糖、药理活性微载体）。最后，也是最重要的，我们证明了局部植入的 MSC 可以有效修复骨、软骨和肌腱。
