journal article

Journal Article

Text

Tissue Engineering - Part A. 2021, 27(21-22), p. 1355-1367

Implantation of Human-Induced Pluripotent Stem Cell-Derived Cartilage in Bone Defects of Mice

Mary Ann Liebert Inc.

English

Text

2021-11-01

https://doi.org/10.1089/ten.tea.2020.0346

This is the accepted version of the following article: Iimori Y., Morioka M., Koyamatsu S., et al. Implantation of Human-Induced Pluripotent Stem Cell-Derived Cartilage in Bone Defects of Mice. Tissue Engineering - Part A 27, 1355 (2021), which has now been formally published in final form at Tissue Engineering - Part A at https://doi.org/10.1089/ten.tea.2020.0346. This original submission version of the article may be used for non-commercial purposes in accordance with the Mary Ann Liebert, Inc., publishers’ self-archiving terms and conditions.

Although bone has an innate capacity for repair, clinical situations such as comminuted fracture, open fracture, or the surgical resection of bone tumors produce critical-sized bone defects that exceed the capacity and require external intervention. Initiating endochondral ossification (EO) by the implantation of a cartilaginous template into the bone defect is a relatively new approach to cure critical-sized bone defects. The combination of chondrogenically primed mesenchymal stromal/stem cells and artificial scaffolds has been the most extensively studied approach for inducing endochondral bone formation in bone defects. In this study, we prepared cartilage (human-induced pluripotent stem [hiPS]-Cart) from hiPS cells (hiPSCs) in a scaffoldless manner and implanted hiPS-Cart into 3.5 mm large defects created in the femurs of immunodeficient mice to examine the repair capacity. For the control, nothing was implanted into the defects. The implantation of hiPS-Cart significantly induced more new bone in the defect compared with the control. Culture periods for the chondrogenic differentiation of hiPSCs significantly affected the speed of bone induction, with less time resulting in faster bone formation. Histological analysis revealed that hiPS-Cart induced new bone formation in a manner resembling EO of the secondary ossification center, with the cartilage canal, which extended from the periphery to the center of hiPS-Cart, initially forming in unmineralized cartilage, followed by chondrocyte hypertrophy at the center. In the newly formed bone, the majority of osteocytes, osteoblasts, and adipocytes expressed human nuclear antigen (HNA), suggesting that these types of cells mainly derived from the perichondrium of hiPS-Cart. Osteoclasts and blood vessel cells did not express HNA and thus were mouse. Finally, integration between the newly formed bone and mouse femur was attained substantially. Although hiPS-Cart induced new bone that filled bone defects, the newly formed bone, which is a hybrid of human and mouse, had not remodeled to mature bone within the observation period of this study (28 weeks).

© Copyright 2021, Mary Ann Liebert, Inc., publishers 2021.

93307

Implantation of Human-Induced Pluripotent Stem Cell-Derived Cartilage in Bone Defects of Mice

Mary Ann Liebert Inc.

English

2021-11-01

Tissue Engineering - Part A

27

21-22

1355

1367

https://doi.org/10.1089/ten.tea.2020.0346

https://hdl.handle.net/11094/93307