Development, Application and Quality Control of Hematopoietic Stem Cell Therapy
CHEN Yue1, HUA Junnan1,2, LIU Chao1,3*
HSCs (hematopoietic stem cells) possess self-renewal capacity and multi-lineage differentiation potential, making them an ideal vehicle in the field of cell and gene therapy. HSC-GT (hematopoietic stem cell gene therapy) involves ex vivo genetic modification of a patient’s autologous HSCs followed by reinfusion, which can correct diseases at the etiological level, achieving “one-time treatment, lifelong benefit” while avoiding the donormatching difficulties and the risk of graft-versus-host disease associated with allogeneic hematopoietic stem cell transplantation. This review systematically outlines the technological evolution of HSC-GT: from the early exploratory applications of γ-retroviral vectors, to the breakthroughs in safety and efficiency achieved by third-generation self-inactivating lentiviral vectors, and to the advent of precision editing technologies including CRISPR-Cas9, base editing, and prime editing. In terms of clinical translation, multiple innovative HSC-GT products have already been approved in the European Union and the United States (including the world’s first CRISPR-based medicine). The therapeutic scope has expanded from hematologic disorders such as hemoglobinopathies and immunodeficiencies to non-hematologic diseases, including lysosomal storage disorders and central nervous system diseases, demonstrating the field’s enormous potential. Quality research and control are critical to the HSC-GT development and manufacturing. These efforts, guided by the principle of “Quality by Design” and compliant with GMP (Good Manufacturing Practice), must focus on four key dimensions: characteristics of HSCs, gene-modification efficacy, cell purity and safety. Moreover, establishing rigorous process controls and final product release standards is essential to ensuring safety, efficacy, and consistency. Looking ahead, HSC-GT is expected to advance toward in vivo gene therapy, expanded indications, and more precise quality assessment systems. With these developments, HSCGT holds promise to evolve from a high-end, personalized therapy into a more accessible and affordable product, providing innovative solutions for numerous refractory diseases.
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