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. CD146⁺CD34⁻CD31⁻CD45⁻pericytes and CD34⁺CD146⁻CD31⁻CD45⁻adventitial 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的干/基质细胞在组织工程领域越来越受到关注。一部分血管周围细胞被公认为具有MSC（间充质干细胞）特征，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，我们研究了两个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 ^-外膜细胞来源于人类脂肪组织，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衍生的 CD146 ⁺周细胞或 CD34 ⁺外膜细胞进行成骨分化和肾小管发生测定。结果表明，与患者匹配的 CD34 ⁺外膜细胞相比，CD146 ⁺周细胞在体外诱导增加的脐带形成和体内血管生成。相反，CD34 ⁺外膜细胞在体外表现出增强的旁分泌诱导的成骨作用。当应用于 NOD/SCID 小鼠的临界尺寸颅骨缺损模型时，CD146 ^{+的联合治疗}具有 CD34 ⁺外膜细胞的周细胞比单独的任何一种细胞类型都导致更大的再骨化。总之，脂肪来源的 CD146 ⁺周细胞和 CD34 ⁺外膜细胞在骨缺损修复中表现出功能不同但重叠和互补的作用。因此，当作为联合细胞疗法应用时，CD146 ⁺周细胞和 CD34 ^{+外膜细胞可能表现出协同骨愈合。}