Endogenus chondrocytes immobilized by G-CSF in nanoporous gels enable repair of critical-size osteochondral defects

Shangkun Tang; Ruinian Zhang; Hanying Bai; Rui Shu; Danying Chen; Ling He; Ling Zhou; Zheting Liao; Mo Chen; Fuxing Pei; Jeremy J Mao; Xiaojun Shi

doi:10.1016/j.mtbio.2023.100933

Endogenus chondrocytes immobilized by G-CSF in nanoporous gels enable repair of critical-size osteochondral defects

Mater Today Bio. 2023 Dec 27:24:100933. doi: 10.1016/j.mtbio.2023.100933. eCollection 2024 Feb.

Authors

Shangkun Tang¹, Ruinian Zhang¹, Hanying Bai², Rui Shu^{2

3}, Danying Chen², Ling He², Ling Zhou⁴, Zheting Liao², Mo Chen², Fuxing Pei¹, Jeremy J Mao^{2

5

6}, Xiaojun Shi¹

Affiliations

¹ Orthopedic Research Institute, Department of Orthopedics, West China Hospital, Sichuan University, Chengdu, 610041, China.
² Center for Craniofacial Regeneration, Columbia University, New York, NY, 10032, USA.
³ West China School/Hospital of Stomatology, Sichuan University, Chengdu,610041, China.
⁴ College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610041, China.
⁵ Department of Biomedical Engineering, Columbia University, New York, NY, USA.
⁶ Department of Pathology and Cell Biology, Columbia University, New York, NY, USA.

Abstract

Injured articular cartilage is a leading cause for osteoarthritis. We recently discovered that endogenous stem/progenitor cells not only reside in the superficial zone of mouse articular cartilage, but also regenerated heterotopic bone and cartilage in vivo. However, whether critical-size osteochondral defects can be repaired by pure induced chemotatic cell homing of these endogenous stem/progenitor cells remains elusive. Here, we first found that cells in the superficial zone of articular cartilage surrounding surgically created 3 × 1 mm defects in explant culture of adult goat and rabbit knee joints migrated into defect-filled fibrin/hylaro1nate gel, and this migration was significantly more robust upon delivery of exogenous granulocyte-colony stimulating factor (G-CSF). Remarkably, G-CSF-recruited chondrogenic progenitor cells (CPCs) showed significantly stronger migration ability than donor-matched chondrocytes and osteoblasts. G-CSF-recruited CPCs robustly differentiated into chondrocytes, modestly into osteoblasts, and barely into adipocytes. In vivo, critical-size osteochondral defects were repaired by G-CSF-recruited endogenous cells postoperatively at 6 and 12 weeks in comparison to poor healing by gel-only group or defect-only group. ICRS and O'Driscoll scores of articular cartilage were significantly higher for both 6- and 12-week G-CSF samples than corresponding gel-only and defect-only groups. Thus, endogenous stem/progenitor cells may be activated by G-CSF, a Food and Drug Administration (FDA)-cleared bone-marrow stimulating factor, to repair osteochondral defects.

Keywords: Chondrogenic progenitor cells; Granulocyte-colony stimulating factor; Osteochondral defects; chondrocyte.