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In recent research studies from Japan and Israel, scientists used stem cells from deciduous teeth, dental pulp, bone marrow and oral mucosa to regenerate mandibular bone in dogs and to colonize infarcted myocardial tissue in rats.1,2 The Japanese researchers reported mature bone formation in adult canine mandibles eight weeks after implanting stem cells that were extracted from the deciduous teeth and dental pulp of canine offspring (puppies). The Israeli scientists transferred stem cells from adult human oral mucosa into myocardial scar tissue samples from rats to examine the stem cells’ capacity to colonize infarcted myocardial tissue. While both studies are preliminary investigations in laboratory animals, they highlight the therapeutic potential and regenerative capacity of multipotent stem cells from the oral cavity.

In the Japanese study, stem cells from deciduous teeth and dental pulp of puppies, plus mesenchymal stem cells from adult canine bone marrow, were implanted in bone defects on a parent canine mandible. Eight weeks after stem cell implantation, mature bone formation and vascularization were observed in the mandibular bone defects of the stem cell-treated adult canine mandibles, when compared with control samples. Mineralized tissues in the stem cell-treated specimens tested positive after eight weeks for osteocalcin, a marker of osteogenesis. The researchers also found that the bone regeneration in canine mandible specimens treated with stem cells from puppies was comparable to that observed in mandibular bone defect sites treated with mesenchymal stem cells from adult canines. In addition, no clinical symptoms of allograft rejection were identified with the child-to-parent transfer of stem cells (i.e., from puppy to adult canine).

The Israeli researchers investigated the capacity of human oral mucosa-derived stem cells to migrate and colonize infarcted myocardial tissue in rats. As explained by the study authors, “stem cells have first to colonize the infarcted tissue in order to exert their biological effects. Cell migration is a paramount biological process required for homogenous colonization of any tissue undergoing repair and/or regeneration.”

In a previous study, members of the same Israeli research team identified a novel source of neural crest stem cells in the lamina propria of adult human oral mucosa.3 Using stem cells from this area, the researchers found in their new study that damaged myocardial tissue in rats could be colonized by stem cells from human oral mucosa, which migrated to the periphery of the damaged cardiac tissue region. Overall, the researchers developed a method for monitoring human-derived oral mucosal stem cell attachment and migration, and quantifying the levels of stem cell colonization in infarcted myocardium specimens from laboratory rats. Based on their observations, the authors suggest that the timing of stem cell administration (e.g., shortly after induction of myocardial infarction in the experimental rats; e.g., within 3 days) could facilitate the tissue colonization process.

Over the past decade, numerous studies have demonstrated that the oral cavity is an accessible and robust location for extracting multipotent stem cells, including stem cells from human exfoliated deciduous teeth, gingival fibroblasts4 and the periodontal ligament. At present, studies point to the tremendous potential of tissue engineering applications for restorative dental care, but extensive scientific and clinical research is still required to confirm the molecular mechanisms of oral stem cell colonization, viability and function in humans. Further research is encouraged in bioengineered tissue applications, including stem cell applications in animal and human models, to assist their development as a future regenerative therapy.

Footnotes

1. Yamada Y, Ito K, Nakamura S, Ueda M, Nagasaka T. Promising cell-based therapy for bone regeneration using stem cells from deciduous teeth, dental pulp, and bone marrow. Cell Transplantation 2011; 20, 1003-1013. Available at: http://www.ingentaconnect.com/content/cog/ct/2011/00000020/00000007/art00002. Accessed September 28, 2011.

2. Gafni Y, Rachima H, Marynka-Kalmani K, Blatt A, Vered Z, Pitaru S. A new in vivo/in vitro model for assessing the capacity of human derived oral mucosa stem cells to colonize the infarcted myocardium. Stem Cell Studies 2011; Volume 1:e6. Available at: http://www.pagepress.org/journals/index.php/scs/article/view/scs.2011.e6. Accessed September 28, 2011.

3. Marynka-Kalmani K, Treves S, Yafee M, Rachima H, Gafni Y, Cohen MA, Pitaru S. The lamina propria of adult human oral mucosa harbors a novel stem cell population. Stem Cells. 2010 May;28(5):984-95. Available at: http://onlinelibrary.wiley.com/doi/10.1002/stem.425/
abstract;jsessionid=FAAD561DA57154C956F571D6DD54BB53.d02t03
. Accessed September 28, 2011. 

4. Egusa H, Okita K, Kayashima H, Yu G, Fukuyasu S, Saeki M, Matsumoto T, Yamanaka S, Yatani H.  Gingival fibroblasts as a promising source of induced pluripotent stem cells. PLoS One 2010 Sep 14;5(9):e12743. Available at: http://www.ncbi.nlm.nih.gov/pubmed/20856871/. Accessed September 28, 2011. 

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Science in the News is a service by the American Dental Association (ADA) to its members to present current information about science topics in the news. The ADA is a professional association of dentists committed to the public’s oral health, ethics, science and professional advancement; leading a unified profession through initiatives in advocacy, education, research and the development of standards. As a science-based organization, the ADA’s evaluation of the scientific evidence may change as more information becomes available. Your thoughts would be greatly appreciated.

Document posted October 2011