Tonsil-derived mesenchymal stem cell-embedded in situ crosslinkable gelatin hydrogel therapy recovers postmenopausal osteoporosis through bone regeneration.

Gyungah Kim,Yoon Shin Park,Yoon Jeong Park,Kyung-Ha Ryu,Da Hyeon Choi,Yunki Lee,Yoon Mi Jin,Inho Jo,Ki Dong Park,Dengshun Miao

doi:10.1371/journal.pone.0200111

Abstract

We investigated therapeutic potential of human tonsil-derived mesenchymal stem cells (TMSC) subcutaneously delivered to ovariectomized (OVX) mice for developing more safe and effective therapy for osteoporosis. TMSC were isolated from tonsil tissues of children undergoing tonsillectomy, and TMSC-embedded in situ crosslinkable gelatin-hydroxyphenyl propionic acid hydrogel (TMSC-GHH) or TMSC alone were delivered subcutaneously to the dorsa of OVX mice. After 3 months, three-dimensionally reconstructed micro-computed tomographic images revealed better recovery of the femoral heads in OVX mice treated with TMSC-GHH. Serum osteocalcin and alkaline phosphatase were also recovered, indicating bone formation only in TMSC-GHH-treated mice, and absence in hypercalcemia or other severe macroscopic deformities showed biocompatibility of TMSC-GHH. Additionally, visceral fat reduction effects by TMSC-GHH further supported their therapeutic potential. TMSC provided therapeutic benefits toward osteoporosis only when embedded in GHH, and showed potential as a supplement or alternative to current therapies.

Highlights

Osteoporosis, a disease in which bones become fragile and very susceptible to breaking, is prevalent among older individuals, especially postmenopausal women [1]
Successful induction of osteoporosis was confirmed by Micro-computed tomographic (microCT) analysis of the hind limb at necropsy, which showed that the femoral head trabeculae of OVX mice were more porous and empty in architecture (Fig 1c) and had lower bone mineral density (BMD) and percent bone volume (Fig 1d)
Based on improvement observed from trabecular images of the femoral head (Fig 4a), these findings suggest that the BMD elevation observed in tonsil-derived mesenchymal stem cells (TMSC)-GHH-treated mice can be considered clinically significant

Summary

Introduction

Osteoporosis, a disease in which bones become fragile and very susceptible to breaking, is prevalent among older individuals, especially postmenopausal women [1]. Tonsil-derived mesenchymal stem cell-embedded hydrogel for bone regeneration the Ministry of Health & Welfare, Republic of Korea (HI16C-2207 to IJ) (URL - http://www.khidi.or.kr); and 3. The Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2017-R1A2B4002611 to YSP) (URL - http://www.nrf.re.kr). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Author Yoon Jeong Park is employed by Nano Intelligent Biomedical Engineering Corporation (NIBEC). Nano Intelligent Biomedical Engineering Corporation (NIBEC) provided support in the form of salary for author YJP, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific role of this author is articulated in the ‘author contributions’ section

Methods

Results

Discussion

Conclusion