Andreani Marco, Testi Manuela, Battarra Mariarosa, Lucarelli Guido
Laboratory of Immunogenetics; IME Foundation at Polyclinic of Tor Vergata Foundation; Rome, Italy.
Chimerism. 2011 Jan;2(1):21-2. doi: 10.4161/chim.2.1.15057.
Previous studies have shown that a stable presence of both donor and recipient haematopoietic derived cells after allogeneic haematopoietic stem cell transplantation (HSCT) occurs in approximately ten percent of the patients affected by β-Thalassemia. Once achieved this condition, defined as persistent mixed chimerism (PMC), the patients do not require additional red blood cells (RBCs) support and, regardless of the presence in some cases of an extremely low percentage of donor-derived nucleated cells, they are clinically cured by an incomplete, but functional graft. Most of the published papers have, however, investigated the impact of donor engraftment in the nucleated cells rather than in the mature erythrocytes. We have recently published a paper showing that in four long-term transplanted patients affected by hemoglobinopathies, characterized by the presence of few donor engrafted nucleated cells-both in the peripheral blood and in the bone marrow-the majority of the erythrocytes were of donor origin. Moreover we showed that the proportion of donor-derived erythroid precursors, determined by analyzing singularly picked-up burst-forming unit erythroid colonies, was equivalent to that observed in the mature nucleated cells rather than in the red blood cells. These results suggest that in patients characterized by the presence of PMC after HSCT a selective advantage of the donor erythroid precursors maturation might successfully contrast the problems bound to the recipient ineffective erythropoiesis. When genetically modified HSCT will be a possible option for treating Thalassemia Major, the co-existence of the repaired cells with those still expressing the genetic defect will be an expected scenario, not in an allogeneic, but in an autologous environment.
先前的研究表明，在接受异基因造血干细胞移植（HSCT）的β地中海贫血患者中，约10%的患者体内会稳定存在供体和受体来源的造血细胞。一旦达到这种状态，即持续混合嵌合体（PMC），患者就不需要额外的红细胞（RBC）支持，并且，尽管在某些情况下供体来源的有核细胞比例极低，但他们通过不完全但有功能的移植物实现了临床治愈。然而，大多数已发表的论文研究的是供体植入对有核细胞的影响，而非对成熟红细胞的影响。我们最近发表了一篇论文，表明在4例长期接受移植的血红蛋白病患者中，其外周血和骨髓中供体植入的有核细胞数量很少，而大多数红细胞却是供体来源的。此外，我们还表明，通过单独分析挑选出的红细胞爆式集落形成单位来确定的供体来源红系祖细胞比例，与在成熟有核细胞中观察到的比例相当，而非与红细胞中的比例相当。这些结果表明，在HSCT后出现PMC的患者中，供体红系祖细胞成熟的选择性优势可能成功对抗与受体无效红细胞生成相关的问题。当基因修饰的HSCT成为治疗重型地中海贫血的一种可能选择时，修复细胞与仍表达基因缺陷的细胞共存将是一种预期情况，这不是在异基因环境中，而是在自体环境中。
