The Application of Cell and Gene-Modified Cell Therapy in the Treatment of Osteopetrosis

Abstract

Bone tissue represents a dynamic tissue that undergoes continuous renewal and remodeling through the coupled actions of osteoblast-driven bone formation and osteoclast-mediated bone resorption. Proper coupling between these two processes is essential for maintaining bone homeostasis, whereas its disruption leads to skeletal pathology. Excessive osteoclast activity underlies disorders such as osteoporosis and Paget’s disease, while osteoclast deficiency, either quantitative or functional, results in osteopetrosis. Osteopetrosis comprises a group of genetically heterogeneous and clinically variable rare metabolic bone diseases characterized by increased bone mass. Clinically, osteopetrosis is commonly classified into severe autosomal recessive osteopetrosis (ARO), also known as infantile malignant osteopetrosis, intermediate ARO, milder autosomal dominant osteopetrosis, and X-linked recessive osteopetrosis. Effective treatment options for both severe and milder forms of osteopetrosis remain an unresolved clinical challenge. This review sheds light on the potential of cell-based and gene-modified cell therapies as emerging strategies for the treatment of osteopetrosis. Current cell-based therapy approaches increasingly focus on induced pluripotent stem cells, while recent advances in gene therapy enable the correction of causative genetic defects through viral vector-mediated gene transfer, CRISPR/Cas9-based genome editing, or RNA interference-mediated gene silencing. In addition, the therapeutic potentials of immunological approaches based on recombinant human interferon gamma-1b is discussed. Despite significant progress, sustained research efforts are still required to translate cell and gene-modified cell therapy into effective and personalized clinical treatments for osteopetrosis.