Nara N, McCulloch E A
J Exp Med. 1985 Nov 1;162(5):1435-43. doi: 10.1084/jem.162.5.1435.
The blast cells of acute myeloblastic leukemia (AML) may be considered as a renewal population, maintained by blast stem cells capable of both self-renewal and the generation of progeny with reduced or absent proliferative potential. Blast progenitor renewal is manifested in suspension culture by an exponential increase in clonogenic cells. This growth requires that two conditions be met: first, the cultures must contain growth factors in media conditioned either by phytohemagglutinin (PHA)-stimulated mononuclear leukocytes (PHA-LCM), or by cells of the continuous bladder carcinoma line HTB9 (HTB9-CM). Second, the cell density must be maintained at 10(6) blasts/ml; this may be achieved by adding irradiated cells to smaller numbers of intact blasts. We are concerned with the mechanism of the feeding function. We present evidence that (a) cell-cell contact is required. (b) Blasts are heterogeneous in respect to their capacity to support growth. (c) Fractions containing membranes from blast cells will substitute for intact cells in promoting the generation of new blast progenitors in culture. (d) This membrane function may be specific for AML blasts, since membranes from blasts of lymphoblastic leukemia or normal marrow cells were inactive.
急性髓细胞白血病(AML)的原始细胞可被视为一个更新群体,由能够自我更新并产生增殖潜能降低或缺失的子代细胞的原始干细胞维持。原始祖细胞的更新在悬浮培养中表现为克隆形成细胞呈指数增长。这种生长需要满足两个条件:首先,培养物必须在由植物血凝素(PHA)刺激的单核白细胞(PHA-LCM)或连续膀胱癌细胞系HTB9(HTB9-CM)条件化的培养基中含有生长因子。其次,细胞密度必须维持在10⁶个原始细胞/毫升;这可以通过向较少数量的完整原始细胞中添加经辐照的细胞来实现。我们关注的是滋养功能的机制。我们提供的证据表明:(a)需要细胞间接触。(b)原始细胞在支持生长的能力方面是异质的。(c)含有原始细胞膜的组分在促进培养中新的原始祖细胞生成方面可替代完整细胞。(d)这种膜功能可能对AML原始细胞具有特异性,因为来自淋巴细胞白血病原始细胞或正常骨髓细胞的膜没有活性。