Figure 7.

The GABBR1 agonist baclofen increases long-term engraftment of human UCB HSPCs. (A) Representative flow cytometry analysis of immunodeficient mouse BM 16 weeks after transplantation with human UCB HSPCs after treatment with vehicle (left) or GABBR1 agonist baclofen (right). Results show percentage engraftment of human CD45⁺ cells (hCD45). (B-C) Dose-dependent engraftment of human hematopoietic CD45⁺ cells (A), and CD34⁺ HSPCs (B). Compared with vehicle controls, the most effective dose is 10 μM baclofen. The GABBR1 antagonist 2-hydroxy-saclofen does not significantly increase engraftment. (D-E) Comparison of engraftment percentage of various hematopoietic populations in BM (D), and spleen (E), at the optimal dose of 10 μM baclofen (red) compared with vehicle control (blue) (n = 5 per group; Student t test; *P < .05; mean = standard error of the mean [SEM]) (see also supplemental Figure 8). Bac, baclofen; Sac, 2-hydroxy-saclofen; SSC-A, side scatter area.