Hayrapetyan Astghik, Surjandi Soraya, Lemsom Evita E P J, Wolters Marleen M M W, Jansen John A, van den Beucken Jeroen J J P
1Department of Biomaterials, Radboudumc, Nijmegen, the Netherlands.
2Department of Biomaterials (309), Radboudumc, Ph van Leijdenlaan 25, Nijmegen, 6525 the Netherlands.
Tissue Eng Regen Med. 2016 Dec 17;13(6):713-723. doi: 10.1007/s13770-016-0008-z. eCollection 2016 Dec.
Cell-based bone regeneration is generally pursued based on single cell type approaches, for which human adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used, owing to their easy accessibility and relatively large yield. In view of multiple cell types involved in physiological bone regeneration, this study aimed to evaluate the osteogenic differentiation of AT-MSCs upon co-culture with endothelial cells or macrophages in a direct or indirect co-culture set-up. Our hypotheses were that 1) endothelial cells and macrophages stimulate AT-MSCs proliferation and osteogenic differentiation and that 2) these two cell types will more profoundly affect osteogenic differentiation of AT-MSCs in a direct compared to an indirect co-culture set-up, because of the possibility for both cell-cell interactions and effects of secreted soluble factors in the former. Osteogenic differentiation of AT-MSCs was stimulated by endothelial cells, particularly in direct co-cultures. Although initial numbers of AT-MSCs in co-culture with endothelial cells were 50% compared to monoculture controls, equal levels of mineralization were achieved. Macrophages showed a variable effect on AT-MSCs behavior for indirect co-cultures and a negative effect on osteogenic differentiation of AT-MSCs in direct co-cultures, the latter likely due to species differences of the cell types used. The results of this study demonstrate potential for cell combination strategies in bone regenerative therapies.
基于细胞的骨再生通常采用单一细胞类型的方法来实现，由于其易于获取且产量相对较高，人脂肪组织来源的间充质基质细胞（AT-MSCs）常用于此。鉴于生理骨再生涉及多种细胞类型，本研究旨在评估在直接或间接共培养体系中，AT-MSCs与内皮细胞或巨噬细胞共培养时的成骨分化情况。我们的假设是：1）内皮细胞和巨噬细胞可刺激AT-MSCs的增殖和成骨分化；2）与间接共培养体系相比，这两种细胞类型在直接共培养体系中对AT-MSCs成骨分化的影响更为显著，因为前者存在细胞间相互作用以及分泌的可溶性因子发挥作用的可能性。内皮细胞可刺激AT-MSCs的成骨分化，尤其是在直接共培养中。尽管与内皮细胞共培养的AT-MSCs初始数量仅为单培养对照的50%，但矿化水平相当。对于间接共培养，巨噬细胞对AT-MSCs的行为表现出不同的影响，而在直接共培养中，巨噬细胞对AT-MSCs的成骨分化产生负面影响，后者可能是由于所用细胞类型的种属差异所致。本研究结果证明了细胞联合策略在骨再生治疗中的潜力。
