Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration

Takamasa Kawai; Wataru Katagiri; Masashi Osugi; Yukiko Sugimura; Hideharu Hibi; Minoru Ueda

doi:10.1016/j.jcyt.2014.11.009

Secretomes from bone marrow-derived mesenchymal stromal cells enhance periodontal tissue regeneration

Cytotherapy. 2015 Apr;17(4):369-81. doi: 10.1016/j.jcyt.2014.11.009. Epub 2015 Jan 14.

Authors

Takamasa Kawai¹, Wataru Katagiri², Masashi Osugi¹, Yukiko Sugimura¹, Hideharu Hibi¹, Minoru Ueda¹

Affiliations

¹ Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.
² Department of Oral and Maxillofacial Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan. Electronic address: w-kat@med.nagoya-u.ac.jp.

PMID: 25595330
DOI: 10.1016/j.jcyt.2014.11.009

Abstract

Background aims: Periodontal tissue regeneration with the use of mesenchymal stromal cells (MSCs) has been regarded as a future cell-based therapy. However, low survival rates and the potential tumorigenicity of implanted MSCs could undermine the efficacy of cell-based therapy. The use of conditioned media from MSCs (MSC-CM) may be a feasible approach to overcome these limitations. The aim of this study was to confirm the effect of MSC-CM on periodontal regeneration.

Methods: MSC-CM were collected during their cultivation. The concentrations of the growth factors in MSC-CM were measured with the use of enzyme-linked immunoassay. Rat MSCs (rMSCs) and human umbilical vein endothelial cells cultured in MSC-CM were assessed on wound-healing and angiogenesis. The expressions of osteogenetic- and angiogenic-related genes of rMSCs cultured in MSC-CM were quantified by means of real-time reverse transcriptase-polymerase chain reaction analysis. In vivo, periodontal defects were prepared in the rat models and the collagen sponges with MSC-CM were implanted.

Results: MSC-CM includes insulin-like growth factor-1, vascular endothelial growth factor, transforming growth factor-β1 and hepatocyte growth factor. In vitro, wound-healing and angiogenesis increased significantly in MSC-CM. The levels of expression of osteogenetic- and angiogenic-related genes were significantly upregulated in rMSCs cultured with MSC-CM. In vivo, in the MSC-CM group, 2 weeks after implantation, immunohistochemical analysis showed several CD31-, CD105-or FLK-1-positive cells occurring frequently. At 4 weeks after implantation, regenerated periodontal tissue was observed in MSC-CM groups.

Conclusions: The use of MSC-CM may be an alternative therapy for periodontal tissue regeneration because several cytokines included in MSC-CM will contribute to many processes of complicated periodontal tissue regeneration.

Keywords: angiogenesis; conditioned medium; mesenchymal stromal cell; migration; paracrine effects; periodontal regeneration.

MeSH terms

Animals
Cell- and Tissue-Based Therapy / methods*
Culture Media, Conditioned / pharmacology
Cytokines / metabolism
Guided Tissue Regeneration, Periodontal / methods*
Hepatocyte Growth Factor / metabolism
Human Umbilical Vein Endothelial Cells
Humans
Insulin-Like Growth Factor I / metabolism
Intercellular Signaling Peptides and Proteins / metabolism
Male
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / drug effects
Mesenchymal Stem Cells / metabolism*
Neovascularization, Physiologic / drug effects
Neovascularization, Physiologic / physiology
Osteogenesis / drug effects
Periodontium / blood supply
Periodontium / physiology*
Rats
Rats, Wistar
Regeneration*
Transforming Growth Factor beta1 / metabolism
Vascular Endothelial Growth Factor A / metabolism

Substances

Culture Media, Conditioned
Cytokines
Intercellular Signaling Peptides and Proteins
Transforming Growth Factor beta1
Vascular Endothelial Growth Factor A
Hepatocyte Growth Factor
Insulin-Like Growth Factor I