Human Fat-Derived Mesenchymal Stem Cells Xenogenically Implanted in a Rat Model Show Enhanced New Bone Formation in Maxillary Alveolar Tooth Defects

Abstract

Background. Due to restorative concerns, bone regenerative therapies have garnered much attention in the field of human oral/maxillofacial surgery. Current treatments using autologous and allogenic bone grafts suffer from inherent challenges, hence the ideal bone replacement therapy is yet to be found. Establishing a model by which MSCs can be placed in a clinically acceptable bone defect to promote bone healing will prove valuable to oral/maxillofacial surgeons. Methods. Human adipose tissue-derived MSCs were seeded onto Gelfoam® and their viability, proliferation, and osteogenic differentiation was evaluated in vitro. Subsequently, the construct was implanted in a rat maxillary alveolar bone defect to assess in vivo bone healing and regeneration. Results. Human MSCs were adhered, proliferated, and uniformly distributed, and underwent osteogenic differentiation on Gelfoam®, comparable with the tissue culture surface. Data confirmed that Gelfoam® could be used as a scaffold for cell attachment and a delivery vehicle to implant MSCs in vivo. Histomorphometric analyses of bones harvested from rats treated with hMSCs showed statistically significant increase in collagen/early bone formation, with cells positive for osteogenic and angiogenic markers in the defect site. This pattern was visible as early as 4 weeks post treatment. Conclusions. Xenogenically implanted human MSCs have the potential to heal an alveolar tooth defect in rats. Gelfoam®, a commonly used clinical biomaterial, can serve as a scaffold to deliver and maintain MSCs to the defect site. Translating this strategy to preclinical animal models provides hope for bone tissue engineering.

Application of Adipose Tissue Stem Cells in Regenerative Dentistry

“…[ 4 ] Likewise, Gelfoam seeded with ADSCs created a three-dimensional environment that favored bone formation. [ 28 ] The scaffold of human amniotic membrane had inherent growth factors that enhanced bone regeneration. [ 7 17 ] The bovine bone and biphasic HA/β-TCP ADSCs were osteoconductive.…”

“…Finally, 33 original studies were reviewed. [ 4 5 6 7 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 ]…”

“…a. Types of studies : Of the 33 included studies, 23 involved the animal models[ 4 5 6 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 ] whereas three trials were done on humans[ 7 29 , 30 ] and seven studies were conducted in vitro [ 31 32 33 34 35 36 37 ] [ Table 1 ].…”

“…d. Cell surface markers expressed by ADSCs : The cell surface markers like CD73, CD90, CD105, CD29 and CD44, CD166, CD54 and CD13 were expressed by ADSCs. [ 6 7 , 9 11 , 13 14 , 16 17 , 20 23 , 24 27 28 29 30 31 32 33 34 35 36 ] However, they did not express hematopoietic antigens like CD34, CD45, CD146, CD31, CD271, CD117, CD106, CD133, CD144, CD309, and HLA-DR.[ 6 7 , 9 11 , 14 16 , 17 20 , 23 24 , 27 28 29 30 31 32 33 34 35 36 ] The expression of stemness genes like SOX2, OCT4, NANOG, and KLF4 was also reported. [ 17 ]…”

“…[ 37 ] Additionally, different types of scaffolds like poly lactic-co-glycolic acid (PLGA), Gelfoam, amniotic membrane, HA/β-TCA, and the bovine bone teeth enhanced the osteogenic potential of ADSCs. [ 4 5 , 7 9 , 14 17 , 28 29 , 36 ]…”