During hematopoietic stem cell transplantation, a substantial number of donor cells are lost because of apoptotic cell death. Transplantation-associated apoptosis is mediated mainly by the proapoptotic BCL-2 family proteins BIM and BMF, and their proapoptotic function is conserved between mouse and human stem and progenitor cells. Permanent inhibition of apoptosis in donor cells caused by the loss of these BH3-only proteins improves transplantation outcome, but recipients might be exposed to increased risk of lymphomagenesis or autoimmunity. Here, we address whether transient inhibition of apoptosis can serve as a safe but efficient alternative to improve the outcome of stem cell transplantation. We show that transient apoptosis inhibition by short-term overexpression of prosurvival BCL-XL, known to block BIM and BMF, is not only sufficient to increase the viability of hematopoietic stem and progenitor cells during engraftment but also improves transplantation outcome without signs of adverse pathologies. Hence, this strategy represents a promising and novel therapeutic approach, particularly under conditions of limited donor stem cell availability.

在造血干细胞移植过程中，大量的供体细胞由于凋亡性细胞死亡而丢失。移植相关的凋亡主要由促凋亡的BCL-2家族蛋白BIM和BMF介导，它们的促凋亡功能在小鼠与人干细胞和祖细胞之间是保守的。由于这些仅BH3蛋白的丢失而导致的永久性抑制供体细胞凋亡改善了移植结果，但受体可能会面临淋巴瘤发生或自身免疫的风险增加。在这里，我们探讨了凋亡的瞬时抑制是否可以作为一种安全而有效的替代方法来改善干细胞移植的结果。我们显示，短期生存抑制性BCL-XL的短暂过度表达会短暂抑制细胞凋亡，已知它会阻止BIM和BMF，不仅增加了移植过程中造血干细胞和祖细胞的活力，而且还改善了移植结果，而没有不良病理迹象。因此，该策略代表了一种有前途且新颖的治疗方法，尤其是在供体干细胞可用性有限的条件下。