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Summary: Bone marrow endothelial cells (BM-ECs) are the essential components of the BM niche and support the function of hematopoietic stem cells (HSCs). However, conditioning for HSC transplantation causes damage to the recipients’ BM-ECs and may lead to transplantation-related morbidity. Here, we investigated the cellular and clonal mechanisms of BM-EC regeneration after irradiative conditioning. Using single-cell RNA sequencing, imaging, and flow cytometry, we revealed how the heterogeneous pool of BM-ECs changes during regeneration from irradiation stress. Next, we developed a single-cell in vitro clonogenic assay and demonstrated that all EC fractions hold a high potential to reenter the cell cycle and form vessel-like structures. Finally, we used Rainbow mice and a machine-learning-based model to show that the regeneration of BM-ECs after irradiation is mostly polyclonal and driven by the broad fraction of BM-ECs; however, the cell output among clones varies at later stages of regeneration.

SIRPa is most commonly known as a phagocytosis inhibitory receptor expressed by myeloid cells. Here the authors show SIRPa is expressed on a subset of CD8+ T cells with higher proliferative and effector activity during the chronic phase of the immune response to viral infection.

Aim: To investigate the impact of timing of same-admission orthotopic heart transplant (OHT) after left ventricular assist device (LVAD) implantation on in-hospital mortality and post-transplant length of stay., Methods: Using data from the Nationwide Inpatient Sample from 1998 to 2011, we identified patients 18 years of age or older who underwent implantation of a LVAD and for whom the procedure date was available. We calculated in-hospital mortality for those patients who underwent OHT during the same admission as a function of time from LVAD to OHT, adjusting for age, sex, race, household income, and number of comorbid diagnoses. Finally, we analyzed the effect of time to OHT after LVAD implantation on the length of hospital stay post-transplant., Results: Two thousand and two hundred patients underwent implantation of a LVAD in this cohort. One hundred and sixty-four (7.5%) patients also underwent OHT during the same admission, which occurred on average 32 d (IQR 7.75-66 d) after LVAD implantation. Of patients who underwent OHT, patients who underwent transplantation within 7 d of LVAD implantation ("early") experienced increased in-hospital mortality (26.8% vs 12.2%, P = 0.0483) compared to patients who underwent transplant after 8 d ("late"). There was no statistically significant difference in age, sex, race, household income, or number of comorbid diagnoses between the early and late groups. Post-transplant length of stay after LVAD implantation was also not significantly different between patients who underwent early vs late OHT., Conclusion: In this cohort of patients who received LVADs, the rate of in-hospital mortality after OHT was lower for patients who underwent late OHT (at least 8 d after LVAD implantation) compared to patients who underwent early OHT. Delayed timing of OHT after LVAD implantation did not correlate with longer hospital stays post-transplant., Competing Interests: Conflict-of-interest statement: Dr. Dipanjan Banerjee reports research support from HeartWare/Medtronic and Thoratec/St. Jude. None of the other listed authors have any disclosures or potential conflicts of interest.