Objectives: Limited biological evidence exists regarding donor host interaction in the periodontal tissue during allogenic tooth germ transplantation. This study aimed to clarify donor host tissue interactions during periodontal tissue healing following tooth germ transplantation.Methods: This study compared the localization of putative stem cells in the periodontal ligament (PDL) by 5-bromo-2'-deoxyuridine (BrdU), Gli1, and periostin immunoreactions using pulse-chase paradigm (BrdU prenatal labeling: peritoneal pulse injections at embryonic days [E] 15-17) in TetOP-H2B-GFP mice (doxycycline administration at E14.5). The current study characterized periodontal tissue healing following allogenic tooth grafts in GFP-labeled donor or host and wild-type mice by pulse-chase paradigm and GFP, BrdU, Gli1, and periostin immunohistochemistry.Results: BrdU prenatal labeling demonstrated that dense label-retaining cells (BrdU-LRCs) disappeared from the PDL by postnatal week 2 (P2W). However, H2B-GFP-LRCs were localized in the PDL of TetOP- H2B GFP mice during P3-8W, and Glil-positive cells in the PDL increased at P2-3W, showing that H2B GFP-LRCs in the PDL are derived from non-proliferating cells during E15-17. Transplanted molars formed cusps and roots and erupted into occlusion by two weeks postoperatively. The junctional epithelium and tooth-related zone of PDL were exclusively composed of donor cells, whereas the PDL alveolar-related zone was a hybrid structure of donor and host cells.Conclusions: The current tooth germ transplantation suggests that the PDL contains putative stem cells, which never proliferate during E15-17, and is composed of resident dental follicle-derived cells and other cell population. (C) 2018 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.