Immunomodulatory properties and in vivo osteogenesis of human dental stem cells from fresh and cryopreserved dental follicles.
In our previous study, dental follicle tissues from extracted wisdom teeth were successfully cryopreserved for use as a source of stem cells. The goals of the present study were to investigate the immunomodulatory properties of stem cells from fresh and cryopreserved dental follicles (fDFCs and cDFCs, respectively) and to analyze in vivo osteogenesis after transplantation of these DFCs into experimental animals. Third passage fDFCs and cDFCs showed similar expression levels of interferon-γ receptor (CD119) and major histocompatibility complex class I and II (MHC I and MHC II, respectively), with high levels of CD119 and MHC I and nearly no expression of MHC II. Both fresh and cryopreserved human DFCs (hDFCs) were in vivo transplanted along with a demineralized bone matrix scaffold into mandibular defects in miniature pigs and subcutaneous tissues of mice. Radiological and histological evaluations of in vivo osteogenesis in hDFC-transplanted sites revealed significantly enhanced new bone formation activities compared with those in scaffold-only implanted control sites. Interestingly, at 8 weeks post-hDFC transplantation, the newly generated bones were overgrown compared to the original size of the mandibular defects, and strong expression of osteocalcin and vascular endothelial growth factor were detected in the hDFCs-transplanted tissues of both animals. Immunohistochemical analysis of CD3, CD4, and CD8 in the ectopic bone formation sites of mice showed significantly decreased CD4 expression in DFCs-implanted tissues compared with those in control sites. These findings indicate that hDFCs possess immunomodulatory properties that involved inhibition of the adaptive immune response mediated by CD4 and MHC II, which highlights the usefulness of hDFCs in tissue engineering. In particular, long-term preserved dental follicles could serve as an excellent autologous or allogenic stem cell source for bone tissue regeneration as well as a valuable therapeutic agent for immune diseases.
Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea.
Young-Hoon
YH
Kang
Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea.
Hye-Jin
HJ
Lee
OBS/Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
Si-Jung
SJ
Jang
Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea.
June-Ho
JH
Byun
Department of Pathology, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
Jong-Sil
JS
Lee
Department of Medical Imaging, College of Veterinary Medicine, Gyeongsang National University, Jinju, Republic of Korea.
Hee-Chun
HC
Lee
Department of Dental Technology, Jinju Health College, Jinju, Republic of Korea.
Won-Uk
WU
Park
Department of Advanced Materials, College of Life Science and Nano Technology, Hannam University, Daejeon, Republic of Korea.
Jin-Ho
JH
Lee
OBS/Theriogenology and Biotechnology, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, Republic of Korea.
Gyu-Jin
GJ
Rho
Department of Oral and Maxillofacial Surgery, School of Medicine and Institute of Health Science, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: parkbw@gnu.ac.kr.
Bong-Wook
BW
Park
D056704:Adaptive Immunity; D000818:Animals; D001861:Bone Regeneration; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D015925:Cryopreservation; D003795:Dental Sac / Q000166:cytology* / Q000276:immunology* / Q000637:transplantation; D005802:Genes, MHC Class II / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D008297:Male; D008334:Mandible / Q000601:surgery; D051379:Mice; D010012:Osteogenesis; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000276:immunology*; D013552:Swine; D013556:Swine, Miniature; D023822:Tissue Engineering; D054457:Tissue Scaffolds
D015704:CD4 Antigens
Dental follicle cells; Immunomodulation; In vivo osteogenesis; Mesenchymal stem cells; Tissue cryopreservation