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

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

doi:10.1371/journal.pone.0200111

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

PLoS One. 2018 Jul 5;13(7):e0200111. doi: 10.1371/journal.pone.0200111. eCollection 2018.

Authors

Gyungah Kim^{1

2}, Yoon Shin Park³, Yunki Lee⁴, Yoon Mi Jin^{1

2}, Da Hyeon Choi³, Kyung-Ha Ryu^{2

5}, Yoon Jeong Park^{6

7}, Ki Dong Park⁴, Inho Jo^{1

2}

Affiliations

¹ Department of Molecular Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
² Ewha Tonsil-derived mesenchymal Stem cells Research Center (ETSRC), College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
³ Major in Microbiology, School of Biological Sciences, College of Natural Sciences, Chungbuk National University, Cheongju, Republic of Korea.
⁴ Department of Molecular Science and Technology, Ajou University, Suwon, Republic of Korea.
⁵ Department of Pediatrics, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
⁶ Department of Dental Regenerative Biotechnology, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, Republic of Korea.
⁷ Central Research Institute, Nano Intelligent Biomedical Engineering Corporation (NIBEC), Seoul, Republic of Korea.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult Stem Cells / physiology*
Alkaline Phosphatase / blood
Animals
Bone Regeneration / physiology
Child
Female
Gelatin / therapeutic use
Humans
Hydrogels / therapeutic use
Mesenchymal Stem Cells / physiology
Mice
Mice, Inbred ICR
Models, Animal
Osteocalcin / blood
Osteoporosis / therapy
Osteoporosis, Postmenopausal / therapy*
Ovariectomy
Palatine Tonsil / metabolism

Substances

Hydrogels
Osteocalcin
Gelatin
Alkaline Phosphatase

Grants and funding

This study was supported in part by: 1. The Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2017M3A9B303636 to IJ) (URL - http://www.nrf.re.kr); 2. The Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by 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.