Abstract: The present invention provides non-thymic endothelial cells (ntECs) engineered to express adenovirus E4ORF1 and/or BMP4, and compositions comprising such engineered ntECs. The present invention also provides methods of using such ntECs in therapy, for example to enhance thymic regeneration (including T cell reconstitution) in subjects in need thereof. Such subjects include those that have a damaged thymus, defective thymic function, insufficient T-cell output, and/or that are immunocompromised—for example as a result of ageing, infection (e.g. with HIV), treatment with radiation therapy, treatment with chemotherapy, or myeloablative conditioning in preparation for an organ/tissue transplant.