Comparing the cost of preparing matched unrelated donor and TCR α+ ß+ /CD19+ depleted donor material for pediatric hematopoietic stem cell transplants in Australia.

Use of TCR α+ ß+ /CD19+ depletion in a pediatric setting has improved the utility of haploidentical donor material, resulting in better rates of engraftment, lower rates of graft vs host disease (GVHD), and improved transplant-related mortality. There are currently no data available on the costs of TCR α+ ß+ /CD19+ depletion. This study assessed the costs of acquiring and preparing TCR α+ ß+ /CD19+ depleted haploidentical donor cells in comparison with matched unrelated donor (MUD) products for use in pediatric patients in Australia. Data from four pediatric transplant centers were used to estimate the resources required for donor work-up, graft acquisition, and laboratory procedures for graft preparation. Information on MUD work-up and graft acquisition was also acquired from these sites and from the national coordinating donor center in Australia. Australian-specific prices and fees were used to estimate total average costs for each transplant type, converted to USD. Preparation of graft material (including work-up, acquisition, and laboratory processes) costs USD 28 963 for TCR α+ ß+ /CD19+ depleted haploidentical grafts and USD 27 297 for MUD grafts. The estimated difference of USD 1666 is largely attributed to the process and consumables to perform TCR α+ ß+ /CD19+ depletion. Given the potential for recipients of TCR α+ ß+ /CD19+ depleted grafts to require minimal GVHD prophylaxis and experience less transplant-related morbidity and mortality, use of TCR α+ ß+ /CD19+ depletion appears favorable despite the higher initial cost. Research is currently ongoing to assess the clinical effectiveness and potential cost-effectiveness of TCR α+ ß+ /CD19+ depletion over a patients' lifetime.

Self-organizing models of human trunk organogenesis recapitulate spinal cord and spine co-morphogenesis.

Integrated in vitro models of human organogenesis are needed to elucidate the multi-systemic events underlying development and disease. Here we report the generation of human trunk-like structures that model the co-morphogenesis, patterning and differentiation of the human spine and spinal cord. We identified differentiation conditions for human pluripotent stem cells favoring the formation of an embryo-like extending antero-posterior (AP) axis. Single-cell and spatial transcriptomics show that somitic and spinal cord differentiation trajectories organize along this axis and can self-assemble into a neural tube surrounded by somites upon extracellular matrix addition. Morphogenesis is coupled with AP patterning mechanisms, which results, at later stages of organogenesis, in in vivo-like arrays of neural subtypes along a neural tube surrounded by spine and muscle progenitors contacted by neuronal projections. This integrated system of trunk development indicates that in vivo-like multi-tissue co-morphogenesis and topographic organization of terminal cell types can be achieved in human organoids, opening windows for the development of more complex models of organogenesis.