Abstract
More than 500 rare genetic bone disorders have been described, but for many of them only limited treatment options are available. Challenges for studying these bone diseases come from a lack of suitable animal models and unavailability of skeletal tissues for studies. Effectors for skeletal abnormalities of bone disorders may be abnormal bone formation directed by osteoblasts or anomalous bone resorption by osteoclasts, or both. Patient-specific induced pluripotent stem cells (iPSCs) can be generated from somatic cells of various tissue sources and in theory can be differentiated into any desired cell type. However, successful differentiation of hiPSCs into functional bone cells is still a challenge. Our group focuses on the use of human iPSCs (hiPSCs) to identify osteoclast defects in craniometaphyseal dysplasia. In this review, we describe the impact of stem cell technology on research for better treatment of such disorders, the generation of hiPSCs from patients with rare genetic bone disorders and current protocols for differentiating hiPSCs into osteoclasts.
Highlights
Studying rare genetic bone disorders is clinically highly relevant
We review some of the rare genetic bone disorders with osteoclast defects, the generation of human iPSCs (hiPSCs) from patients with rare genetic bone disorders and the protocols for differentiating hiPSC into osteoclasts
Inducing hematopoiesis from human embryonic stem cells or hiPSCs has been reported by several extensive studies using three systems: (1) differentiation by coculturing hESC/hiPSCs with stromal cells; (2) differentiation through formation of embryoid bodies (EB), which can be differentiated into the three germ layers including mesoderm; (3) differentiation by monolayer culture of hESCs/hiPSCs on extracellular matrix protein coated-plates, such as collagen IV
Summary
Individual diseases only affect a small percentage of the population (less than 200,000 people or about 1 in 1500 people in the United States), overall, a large number of people suffer from these skeletal disorders due to their frequency (almost 500 rare genetic bone disorders listed by NIH Office of Rare Disease Research). The diverse expressivities of clinical manifestations, from lethality of newborns to mild skeletal abnormalities, make the diagnosis of some of these disorders challenging Most of these rare bone diseases are understudied due to the rarity of human specimens and unavailable animal models, and treatment options are often limited or lacking. We review some of the rare genetic bone disorders with osteoclast defects, the generation of hiPSCs from patients with rare genetic bone disorders and the protocols for differentiating hiPSC into osteoclasts
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