Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan; Department of Oral Rehabilitation, Fukuoka Dental College, Fukuoka, Japan.
Oral Medicine Research Center, Fukuoka Dental College, Fukuoka, Japan; Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan.
Cytotherapy. 2021 Jul;23(7):608-616. doi: 10.1016/j.jcyt.2021.02.115.
Mesenchymal stem/stromal cells (MSCs) are multipotent and self-renewing cells that are extensively used in tissue engineering. Adipose tissues are known to be the source of two types of MSCs; namely, adipose tissue-derived MSCs (ASCs) and dedifferentiated fat (DFAT) cells. Although ASCs are sometimes transplanted for clinical cytotherapy, the effects of DFAT cell transplantation on mandibular bone healing remain unclear.
The authors assessed whether DFAT cells have osteogenerative potential compared with ASCs in rats in vitro. In addition, to elucidate the ability of DFAT cells to regenerate the jaw bone, the authors examined the effects of DFAT cells on new bone formation in a mandibular defect model in (i) 30-week-old rats and (ii) ovariectomy-induced osteoporotic rats in vivo.
Osteoblast differentiation with bone morphogenetic protein 2 (BMP-2) or osteogenesis-induced medium upregulated the osteogenesis-related molecules in DFAT cells compared with those in ASCs. BMP-2 activated the phosphorylation signaling pathways of ERK1/2 and Smad2 in DFAT cells, but minor Smad1/5/9 activation was noted in ASCs. The transplantation of DFAT cells into normal or ovariectomy-induced osteoporotic rats with mandibular defects promoted new bone formation compared with that seen with ASCs.
DFAT cells promoted osteoblast differentiation and new bone formation through ERK1/2 and Smad2 signaling pathways in vitro. The transplantation of DFAT cells promoted new mandibular bone formation in vivo compared with that seen with ASCs. These results suggest that transplantation of ERK1/2-activated DFAT cells shorten the mandibular bone healing process in cytotherapy.
间充质干细胞（MSCs）是多能且自我更新的细胞，广泛应用于组织工程。脂肪组织是两种类型的 MSCs 的来源，即脂肪组织来源的间充质干细胞（ASCs）和去分化脂肪（DFAT）细胞。虽然 ASCs 有时被用于临床细胞治疗，但 DFAT 细胞移植对下颌骨愈合的影响尚不清楚。
作者在体外评估了 DFAT 细胞与 ASC 相比是否具有成骨潜能。此外，为了阐明 DFAT 细胞再生颌骨的能力，作者在体内研究了 DFAT 细胞对（i）30 周龄大鼠下颌骨缺损模型和（ii）去卵巢诱导骨质疏松大鼠下颌骨缺损模型中新骨形成的影响。
骨形态发生蛋白 2（BMP-2）或成骨诱导培养基诱导成骨分化，使 DFAT 细胞中的成骨相关分子上调，高于 ASC 细胞。BMP-2 激活了 DFAT 细胞中 ERK1/2 和 Smad2 的磷酸化信号通路，但在 ASC 细胞中仅观察到微小的 Smad1/5/9 激活。DFAT 细胞移植到正常或去卵巢诱导骨质疏松大鼠的下颌骨缺损中，与 ASC 相比，促进了新骨形成。
DFAT 细胞通过 ERK1/2 和 Smad2 信号通路在体外促进成骨细胞分化和新骨形成。与 ASC 相比，DFAT 细胞的移植促进了体内新的下颌骨形成。这些结果表明，ERK1/2 激活的 DFAT 细胞移植可缩短细胞治疗中的下颌骨愈合过程。
