Co-cultured spheroids of human periodontal ligament mesenchymal stem cells and vascular endothelial cells enhance periodontal tissue regeneration

Kotaro Sano; Michihiko Usui; Yuki Moritani; Kohji Nakazawa; Tomoya Hanatani; Hisataka Kondo; Mitsushiro Nakatomi; Satoru Onizuka; Takanori Iwata; Tsuyoshi Sato; Akifumi Togari; Wataru Ariyoshi; Tatsuji Nishihara; Keisuke Nakashima

Regenerative Therapy (Jun 2020)

Co-cultured spheroids of human periodontal ligament mesenchymal stem cells and vascular endothelial cells enhance periodontal tissue regeneration

Kotaro Sano,
Michihiko Usui,
Yuki Moritani,
Kohji Nakazawa,
Tomoya Hanatani,
Hisataka Kondo,
Mitsushiro Nakatomi,
Satoru Onizuka,
Takanori Iwata,
Tsuyoshi Sato,
Akifumi Togari,
Wataru Ariyoshi,
Tatsuji Nishihara,
Keisuke Nakashima

Affiliations

Kotaro Sano: Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Michihiko Usui: Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan; Corresponding author. Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, 803-8580, Japan.
Yuki Moritani: Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Kohji Nakazawa: Department of Life and Environment Engineering, The University of Kitakyushu, 1-1 Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan
Tomoya Hanatani: Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Hisataka Kondo: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan
Mitsushiro Nakatomi: Division of Anatomy, Department of Health Improvement, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Satoru Onizuka: Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Takanori Iwata: Department of Periodontology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan
Tsuyoshi Sato: Department of Oral and Maxillofacial Surgery, Saitama Medical University, 38 Morohongo, Moroyama-machi, Iruma-gun, Saitama 350-0495, Japan
Akifumi Togari: Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan
Wataru Ariyoshi: Division of Infection and Molecular Biology, Department of Health Improvement, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Tatsuji Nishihara: Division of Infection and Molecular Biology, Department of Health Improvement, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan
Keisuke Nakashima: Division of Periodontology, Department of Oral Function, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka 803-8580, Japan

Journal volume & issue: Vol. 14
pp. 59 – 71

Abstract

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Introduction: Human periodontal ligament mesenchymal stem cells (hPDLMSCs) have been known that they play important roles in homeostasis and regeneration of periodontal tissues. Additionally, spheroids are superior to monolayer-cultured cells. We investigated the characteristics and potential of periodontal tissue regeneration in co-cultured spheroids of hPDLMSCs and human umbilical vein endothelial cells (HUVECs) in vitro and in vivo. Methods: Co-cultured spheroids were prepared with cell ratios of hPDLMSCs: HUVECs = 1:1, 1:2, and 2:1, using microwell chips. Real-time polymerase chain reaction (PCR) analysis, Enzyme-Linked Immuno Sorbent Assay (ELISA), and nodule formation assay were performed to examine the properties of co-cultured spheroids. Periodontal tissue defects were prepared in the maxillary first molars of rats and subjected to transplantation assay. Results: The expression levels of stemness markers, vascular endothelial growth factor (VEGF), osteogenesis-related genes were up-regulated in co-cultured spheroids, compared with monolayer and spheroid-cultured hPDLMSCs. The nodule formation was also increased in co-cultured spheroids, compared with monolayer and spheroid cultures of hPDLMSCs. Treatment with co-cultured spheroids enhanced new cementum formation after 4 or 8 weeks of transplantation, although there was no significant difference in the new bone formation between co-cultured spheroids and hPDLMSC spheroids. Conclusions: We found that co-cultured spheroids enhance the periodontal tissue regeneration. Co-cultured spheroids of hPDLMSCs and HUVECs may be a useful therapy that can induce periodontal tissue regeneration.

Published in Regenerative Therapy

ISSN: 2352-3204 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Biology (General): Cytology
Website: http://www.journals.elsevier.com/regenerative-therapy/

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