Jiang Yuehua, Vaessen Ben, Lenvik Todd, Blackstad Mark, Reyes Morayma, Verfaillie Catherine M
Stem Cell Institute, Department of Medicine, University of Minnesota Medical School, Minneapolis 55455, USA.
Exp Hematol. 2002 Aug;30(8):896-904. doi: 10.1016/s0301-472x(02)00869-x.
Recent studies have shown that cells from bone marrow (BM), muscle, and brain may have greater plasticity than previously known. We have identified multipotent adult progenitor cells (MAPC) in postnatal human and rodent BM that copurify with mesenchymal stem cells (MSC). BM MAPC proliferate without senescence and differentiate into mesodermal, neuroectodermal, and endodermal cell types. We hypothesized that cells with characteristics similar to BM MAPC can be selected and cultured from tissues other than BM.
BM, whole brain, and whole muscle tissue was obtained from mice. Cells were plated on Dulbecco modified Eagle medium supplemented with 2% fetal calf serum and 10 ng/mL epidermal growth factor (EGF), 10 ng/mL platelet-derived growth factor (PDGF-BB), and 1000 units/mL leukemia inhibitory factor (LIF) for more than 6 months. Cells were maintained between 0.5 and 1.5 x 10(3) cells/cm(2). At variable time points, we tested cell phenotype by FACS and evaluated their differentiation into endothelial cells, neuroectodermal cells, and endodermal cells in vitro. We also compared the expressed gene profile in BM, muscle, and brain MAPC by Affimetrix gene array analysis.
Cells could be cultured from BM, muscle, and brain that proliferated for more than 70 population doublings (PDs) and were negative for CD44, CD45, major histocompatibility complex class I and II, and c-kit. Cells from the three tissues differentiated to cells with morphologic and phenotypic characteristics of endothelium, neurons, glia, and hepatocytes. The expressed gene profile of cells derived from the three tissues was identical (r(2) > 0.975).
This study shows that cells with MAPC characteristics can be isolated not only from BM, but also from brain and muscle tissue. Whether MAPC originally derived from BM are circulating or all organs contain stem cells with MAPC characteristics currently is being studied. Presence of MAPC in multiple tissues may help explain the "plasticity" found in multiple adult tissues.
最近的研究表明，来自骨髓（BM）、肌肉和大脑的细胞可能具有比以前所知更大的可塑性。我们已经在出生后的人类和啮齿动物骨髓中鉴定出多能成人祖细胞（MAPC），它们与间充质干细胞（MSC）共同纯化。骨髓MAPC可无衰老地增殖，并分化为中胚层、神经外胚层和内胚层细胞类型。我们假设可以从骨髓以外的组织中选择并培养出具有与骨髓MAPC相似特征的细胞。
从小鼠获取骨髓、全脑和全肌肉组织。将细胞接种在补充有2%胎牛血清、10 ng/mL表皮生长因子（EGF）、10 ng/mL血小板衍生生长因子（PDGF-BB）和1000单位/mL白血病抑制因子（LIF）的杜氏改良 Eagle 培养基上培养超过6个月。细胞维持在0.5至1.5×10³个细胞/cm²之间。在不同时间点，我们通过流式细胞术（FACS）检测细胞表型，并评估它们在体外向内皮细胞、神经外胚层细胞和内胚层细胞的分化情况。我们还通过Affimetrix基因芯片分析比较了骨髓、肌肉和大脑MAPC中的基因表达谱。
可以从骨髓、肌肉和大脑中培养出细胞，这些细胞增殖超过70个群体倍增（PDs），并且CD44、CD45、主要组织相容性复合体I类和II类以及c-kit均为阴性。来自这三种组织的细胞分化为具有内皮、神经元、神经胶质和肝细胞形态及表型特征的细胞。来自这三种组织的细胞的基因表达谱相同（r²>0.975）。
本研究表明，具有MAPC特征的细胞不仅可以从骨髓中分离，还可以从大脑和肌肉组织中分离。目前正在研究最初源自骨髓的MAPC是循环的，还是所有器官都含有具有MAPC特征的干细胞。多种组织中存在MAPC可能有助于解释在多个成体组织中发现的“可塑性”。
