Salner A L, Obbagy J E, Hellman S
J Natl Cancer Inst. 1982 Apr;68(4):639-41.
The success of bone marrow transplantation depends not only on the engraftment of adequate numbers of hematopoietic stem cells but also on their self-renewal capacity, which must be sufficient to provide lifetime hematopoiesis. The lectin peanut agglutinin (PNA), when exposed to bone marrow, causes separation into two distinct fractions. The agglutinated fraction not only is enriched with colony-forming units--spleen but also is devoid of graft-versus-host (GVH) activity when injected into allogeneic lethally irradiated recipients, and therefore, it is considered to be an ideal source for bone marrow transplantation. The absence of GVH activity is presumably due to the separation of mature thymocytes into the nonagglutinated fraction and functionally immature thymocytes into the agglutinated fraction. Although there has been speculation that immature hematopoietic stem cells also selectively bind to PNA, other evidence suggests that the relationship of lectin binding specificity to level of maturity varies in different tissues. This study was performed to assess the self-renewal capacity of lectin-separated bone marrow stem cells. Results indicate that the self-renewal of the agglutinated fraction is significantly lower than that of the unfractionated bone marrow; such self-renewal of the nonagglutinated fraction is higher. This is further evidence for the heterogeneity of the stem cell pool. Stem cell enrichment should not be the goal in bone marrow transplantation; rather, the goal should be utilization of stem cells with the greatest self-renewal potential.
骨髓移植的成功不仅取决于足够数量造血干细胞的植入,还取决于它们的自我更新能力,这种能力必须足以维持终身造血。凝集素花生凝集素(PNA)与骨髓接触时,会使其分离成两个不同的部分。凝集部分不仅富含脾集落形成单位,而且注入同种异体致死性照射受体后缺乏移植物抗宿主(GVH)活性,因此,它被认为是骨髓移植的理想来源。缺乏GVH活性可能是由于成熟胸腺细胞分离到未凝集部分,而功能不成熟的胸腺细胞分离到凝集部分。尽管有人推测未成熟造血干细胞也选择性地与PNA结合,但其他证据表明凝集素结合特异性与成熟水平的关系在不同组织中有所不同。本研究旨在评估凝集素分离的骨髓干细胞的自我更新能力。结果表明,凝集部分的自我更新明显低于未分离的骨髓;未凝集部分的自我更新则较高。这进一步证明了干细胞池的异质性。骨髓移植的目标不应是富集干细胞;相反,目标应该是利用具有最大自我更新潜力的干细胞。