Cellular specificity of the cure for osteopetrosis: isolation of and treatment with pluripotent hemopoietic stem cells.
Cellular specificity of the cure for osteopetrosis: isolation of and treatment with pluripotent hemopoietic stem cells.
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治疗石骨症的细胞特异性：多能造血干细胞的分离和治疗。
DOI：
10.1016/8756-3282(85)90007-9
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发表时间：
1985
期刊：
影响因子：
4.1
通讯作者：
Schneider,GB
中科院分区：
文献类型：
--
作者：
Schneider,GB
骨质疏松症是由于异常破骨细胞导致骨吸收减少的结果。对iamutant的研究表明，来自正常同窝小鼠的单核细胞可以治愈骨骼硬化症，并在移植到小鼠体内时导致正常破骨细胞的形成。最近的研究表明，脾脏、骨髓和新生肝脏的聚蔗糖-泛影葡胺分离物可有效治疗骨骼疾病。这些结果表明治愈的细胞来源是多能造血干细胞（PHSC）。戈德施奈德等人。 (1980) 证明来自大鼠骨髓的干细胞是相对较大的单核细胞，对 Thy 1.1 抗原呈强阳性。使用针对大鼠 Thy 1.1 抗原和豚鼠补体开发的单克隆抗体处理来自正常大鼠的脾脏和骨髓样本。该过程对 47% 的单核脾细胞和 74% 的单核骨髓细胞具有细胞毒性。当将Thy 1.1耗尽的样本移植到同窝小鼠中时，它们在逆转破骨细胞和骨吸收缺陷方面无效。使用 Goldschneider 描述的参数和荧光激活细胞分选 (FACS)，从正常大鼠骨髓中分离出 PHSC。对分离的细胞进行集落形成单位——脾 (CFU-S) 分析，发现含有大约 65-70% 的 PHSC。对2、3和5周龄的大鼠进行腹腔注射正常骨髓干细胞（1.4×104至7.0×104细胞）。通过放射线照相、测量胫骨骨髓腔的大小以及移植后 3 周鉴定活性（表型正常）破骨细胞来评估治疗效果。在所有移植年龄和所有测试的细胞数量下，干细胞悬浮液都能有效治疗骨质疏松症。这些积极的发现以及 Thy 1.1 耗尽细胞无效的事实表明 PHSC 是治愈突变的细胞来源。
Osteopetrosis in theiarat is the result of reduced bone resorption due to abnormal osteoclasts. Studies in theiamutant have shown that mononuclear cells from normal littermates could cure the skeletal sclerosis and result in the formation of normal osteoclasts when transplanted intoiarats. Recent studies demonstrated that the Ficoll-Hypaque isolates of spleen, bone marrow, and newborn liver were effective in curing the skeletal disease. These results suggest that the cellular source of the cure is a pluripotent hemopoietic stem cell (PHSC). Goldschneider et al. (1980) demonstrated that stem cells from rat bone marrow relatively large mononuclear cells that are strongly positive for Thy 1.1 antigen. Splenic and bone marrow samples from normal rats were treated with a monoclonal antibody developed against the rat Thy 1.1 antigen and guinea pig complement. This procedure was cytotoxic for 47% of the mononuclear spleen cells and 74% of the mononuclear bone marrow cells. When the Thy 1.1 depleted samples were transplanted intoialittermates, they were ineffective in reversing the osteoclast and bone resorption defects. Using the parameters described by Goldschneider, and fluorescence-activated cell sorting (FACS), the PHSC were isolated from normal rat bone marrow. The isolated cells were assayed for colony forming units — spleen (CFU-S) and were found to contain approximately 65–70% PHSC. Two, 3, and 5-week-oldiarats were given an intraperitoneal injection of normal bone marrow stem cells (1.4 × 104to 7.0 × 104cells). The effects of treatment were evaluated by radiography, by measuring the size of the tibial marrow cavity, and by identifying active (phenotypically normal) osteoclasts at 3 weeks after transplantation. At all of the ages transplanted and at all of the cell numbers tested, the stem cell suspensions were effective in curing the osteopetrotic condition. These positive findings and the fact that the Thy 1.1 depleted cells were ineffective suggests that the PHSC is a cellular source of the cure in theiamutation.