SummaryHematopoietic stem cell (HSC) transplantation is a curative treatment for a variety of blood and immune disorders. Currently available methods to obtain donor HSCs are suboptimal, and the limited supply of donor HSCs hampers the success and availability of HSC transplantation therapies. We recently showed that manipulation of vascular integrity can be employed to induce HSC mobilization from the bone marrow to the blood stream, facilitating non-invasive collection of HSCs. Here, we tested whether FDA-approved vasodilators are capable of mobilizing HSCs. We found that a rapid, 2-h regimen of a single oral dose of Viagra (sildenafil citrate) combined with a single injection of the CXCR4 antagonist AMD3100 leads to efficient HSC mobilization at levels rivaling the standard-of-care 5-day regimen of granulocyte-colony stimulating factor (G-CSF/Filgrastim/Neupogen). Our findings solidify vascular integrity as an essential regulator of HSC trafficking and provide an attractive, single-day regimen for HSC mobilization using already FDA-approved drugs.

Hematopoietic stem cell (HSC) trafficking is regulated by a number of complex mechanisms. Among them are the transmembrane protein Robo4 and the vascular cell adhesion molecule, VCAM1. Endothelial VCAM1 is a well-known regulator of hematopoietic cell trafficking, and our previous studies revealed that germline deletion of Robo4 led to impaired HSC trafficking, with an increase in vascular endothelial cell (VEC) numbers and downregulation of VCAM1 protein on sinusoidal VECs. Here, we utilized two Robo4 conditional deletion models in parallel with Robo4 germline knockout mice (R4KO) to evaluate the effects of acute and endothelial cell-specific Robo4 deletion on HSC trafficking. Strikingly similar to the R4KO, the acute deletion of Robo4 resulted in altered HSC distribution between the bone marrow and blood compartments, despite normal numbers of VECs and wild-type levels of VCAM1 cell surface protein on sinusoidal VECs. Additionally, consistent with the R4KO mice, acute loss of Robo4 in the host perturbed long-term engraftment of donor wild-type HSCs and improved HSC mobilization to the peripheral blood. These data demonstrate the significant role that endothelial Robo4 plays in directional HSC trafficking, independent of alterations in VEC numbers and VCAM1 expression.

Background Effective leadership is crucial for improving the quality of health professionals trained in Sub-Saharan Africa (SSA). However, many health professions training institutions lack formal faculty mentorship programs for leaders, leaving faculty to learn on the job without formal support. To address this gap, the African Forum for Research and Education in Health (AFREhealth) developed an innovative leadership capacity-strengthening program, named after the late educator and research, James Hakim. Objective This article describes the design and implementation of the AFREhealth leadership training program and how it could bridge the leadership skills gap in health professions education in SSA. The objective of the article is to describe the program’s implementation process, share the experiences of participants, and discuss lessons learned. Methods The AFREhealth leadership training program was developed through consultative meetings, after a landscape review of existing leadership training programs. The program was designed to be delivered virtually over a 12-week period, and the curriculum included modules on leadership styles and personality, mentorship, change management, conflict management, budgeting, resource mobilization, building partnerships, inter-professional education & collaborative practice, and working on inter-professional teams. Training activities included weekly workshops, small group discussions, readings, reflective sessions with senior health leaders/experts, focused mentorship sessions, and a guided project design capstone. Surveys were conducted to obtain feedback from participants and assess the program’s impact on their ongoing leadership roles in their institutions. Results The leadership training program was implemented twice in a 20-month period, with 68 trainees completing the program. Participants reported increased knowledge, skills, and confidence in attaining key leadership competencies. The virtual delivery of the training allowed for a wide pool of applicants to participate, and the curriculum was designed to be adaptable for other institutions. Conclusion The AFREhealth leadership development program demonstrated the need for mentoring health professions education leaders in Africa and the effectiveness of virtual training methods. The innovative curriculum and delivery model provide a valuable resource for other institutions seeking to build leadership capacity in health professions education.