Spleno-Medullary Progenitor Cell Transplantation (SMPT): A Mechanistically Grounded Theoretical Framework for Autologous Restoration of Erythropoiesis in Severe Aplastic Anemia and Diamond-Blackfan Anemia

We present a novel in silico conceptual framework for spleno-medullary progenitor cell transplantation (SMPT) as a targeted autologous intervention to restore red blood cell (RBC) production in severe aplastic anemia (SAA) and Diamond-Blackfan anemia (DBA). The approach hypothesizes exploitation of the spleen's latent reservoir of stress-adapted erythroid progenitors—harvested, ex-vivo expanded, and re-infused into a cytokine-primed marrow niche. This may circumvent autoimmune HSPC destruction in SAA and potentially mitigate ribosomal biogenesis defects in DBA through niche-mediated compensatory mechanisms, while eliminating allogeneic risks.A four-compartment deterministic/stochastic ODE/SDE model, parameterized from peer-reviewed kinetic data and subjected to global sensitivity analysis (Sobol indices), Bayesian posterior inference, and Monte-Carlo uncertainty quantification, predicts restoration of normalized RBC counts to R(200)≈247.72 (arbitrary units) from near-zero baseline under stated assumptions. All derivations, parameters, Python code, and simulation outputs are computationally reproducible. This manuscript provides a mechanistically grounded theoretical foundation for future experimental validation of niche-engineered autologous therapies in bone marrow failure syndromes.