Three-dimensional bioprinted bone marrow constructs: a new frontier in modeling Aplastic anemia microenvironments

To the Editor, Aplastic anemia (AA) affects ~2 individuals/million people in Europe and North America, with 2–3 fold higher incidence reported in East Asia. Characterized by bone marrow hypocellularity and pancytopenia, AA causes morbidity and mortality because of immune-mediated destruction of hematopoietic stem and progenitor cells (HSPCs). Presently used two-dimensional (2D) cultures and murine systems are fail to replicate the human bone marrow (BM) structural complexity and dynamic microenvironment [1]. Developing technology in 3D bioprinting has the ability to mimic the BM microarchitecture and enables specific spatial arrangement of stromal cells, extracellular matrix components, and vasculature within hydrogels such as alginate-collagen blends (Table 1). The BM constructs can be developed to replicate individual disease conditions using patient-derived or genetically engineered cell lines (Table 1). The layer-by-layer arrangement allows reconstruction of specific zones of BM, including sinusoidal, arteriolar, and endosteal regions, each contributing uniquely to HSPC maintenance and immune cell interaction [2] (Table 1).Table 1: Comparative overview of Aplastic anemia modeling platforms [2,3]Integration of immune effectors into 3D constructs, BM can be useful for modeling of T-cell mediated stem cell depletion that shows acquired AA (Table 1). Incorporation of combine cytokine such as interferon-gamma, tumor necrosis factor-alpha, and interleukin-17 has the ability to recreate the pro-inflammatory environment seen in patient BM. Addition of mesenchymal stromal cells (MSCs) within 3 d bioprinted BM constructs further enables evaluation of immunomodulatory and regenerative therapies such as eltrombopag or anti-thymocyte globulin [3]. Noninvasive imaging methods such as fluorescent live-cell imaging and diffusion tensor imaging can be used and beneficial for real-time evaluation of HSPCs viability, proliferation, and spatial migration to enhance monitoring. These perception helps in important advantages in tracking treatment response and study the disease progression. Challenges to widespread adoption include standardization of bioinks compatible with hematopoietic cells, ensuring long-term viability of printed constructs, and validation of in vitro findings in clinical settings. Development of open-source bioprinting protocols and cost-effective hardware may facilitate broader implementation across research laboratories [4]. In conclusion, the application of 3D bioprinted BM constructed models for AA provides a transformative innovation with significant clinical implications. By accurately recapitulating patient-specific disease environments, this platform has a potential to revolutionize disease modeling, therapy testing, and personalized treatment strategies in hematology. Financial support and sponosorship Nil. Conflicts of interest There are no conflicts of interest.