Wang Yiyun, Xu Jiajia, Chang Leslie, Meyers Carolyn A, Zhang Lei, Broderick Kristen, Lee Min, Peault Bruno, James Aaron W
1Department of Pathology, Johns Hopkins University, 21205 Baltimore, MD USA.
2Department of Plastic Surgery, Johns Hopkins University, 21205 Baltimore, MD USA.
NPJ Regen Med. 2019 Jan 7;4:1. doi: 10.1038/s41536-018-0063-2. eCollection 2019.
Pericytes and other perivascular stem/stromal cells are of growing interest in the field of tissue engineering. A portion of perivascular cells are well recognized to have MSC (mesenchymal stem cell) characteristics, including multipotentiality, self-renewal, immunoregulatory functions, and diverse roles in tissue repair. Here, we investigate the differential but overlapping roles of two perivascular cell subsets in paracrine induction of bone repair. CD146CD34CD31CD45pericytes and CD34CD146CD31CD45adventitial cells were derived from human adipose tissue and applied alone or in combination to calvarial bone defects in mice. In vitro, osteogenic differentiation and tubulogenesis assays were performed using either fluorescence activated cell sorting-derived CD146 pericytes or CD34 adventitial cells. Results showed that CD146 pericytes induced increased cord formation in vitro and angiogenesis in vivo in comparison with patient-matched CD34 adventitial cells. In contrast, CD34 adventitial cells demonstrated heightened paracrine-induced osteogenesis in vitro. When applied in a critical-size calvarial defect model in NOD/SCID mice, the combination treatment of CD146 pericytes with CD34 adventitial cells led to greater re-ossification than either cell type alone. In summary, adipose-derived CD146 pericytes and CD34 adventitial cells display functionally distinct yet overlapping and complementary roles in bone defect repair. Consequently, CD146 pericytes and CD34 adventitial cells may demonstrate synergistic bone healing when applied as a combination cellular therapy.
周细胞和其他血管周围干细胞/基质细胞在组织工程领域越来越受到关注。人们普遍认识到，一部分血管周围细胞具有间充质干细胞（MSC）的特性，包括多能性、自我更新、免疫调节功能以及在组织修复中的多种作用。在这里，我们研究了两种血管周围细胞亚群在旁分泌诱导骨修复中的不同但重叠的作用。CD146⁺CD34⁻CD31⁻CD45⁻周细胞和CD34⁺CD146⁻CD31⁻CD45⁻外膜细胞来源于人脂肪组织，并单独或联合应用于小鼠颅骨缺损。在体外，使用荧光激活细胞分选获得的CD146周细胞或CD34外膜细胞进行成骨分化和血管生成试验。结果表明，与患者匹配的CD34外膜细胞相比，CD146周细胞在体外诱导更多的条索形成，在体内诱导更多的血管生成。相反，CD34外膜细胞在体外表现出更强的旁分泌诱导成骨作用。当应用于NOD/SCID小鼠的临界大小颅骨缺损模型时，CD146周细胞与CD34外膜细胞联合治疗比单独使用任何一种细胞类型都能导致更大程度的再骨化。总之，脂肪来源的CD146周细胞和CD34外膜细胞在骨缺损修复中发挥功能上不同但重叠和互补的作用。因此，CD146周细胞和CD34外膜细胞作为联合细胞疗法应用时可能显示出协同的骨愈合效果。
