Department of Pathology, Johns Hopkins University, Baltimore, Maryland, USA.
Orthopaedic and Trauma Surgery Unit, Department of Surgery, Dentistry, Paediatrics and Gynaecology of the University of Verona, Verona, Italy.
Stem Cells Transl Med. 2020 Dec;9(12):1617-1630. doi: 10.1002/sctm.20-0152. Epub 2020 Jul 22.
The vascular wall stores mesenchymal progenitor cells which are able to induce bone regeneration, via direct and paracrine mechanisms. Although much is known regarding perivascular cell regulation of osteoblasts, their regulation of osteoclasts, and by extension utility in states of high bone resorption, is not known. Here, human perivascular stem cells (PSCs) were used as a means to prevent autograft resorption in a gonadectomy-induced osteoporotic spine fusion model. Furthermore, the paracrine regulation by PSCs of osteoclast formation was evaluated, using coculture, conditioned medium, and purified extracellular vesicles. Results showed that PSCs when mixed with autograft bone induce an increase in osteoblast:osteoclast ratio, promote bone matrix formation, and prevent bone graft resorption. The confluence of these factors resulted in high rates of fusion in an ovariectomized rat lumbar spine fusion model. Application of PSCs was superior across metrics to either the use of unpurified, culture-defined adipose-derived stromal cells or autograft bone alone. Under coculture conditions, PSCs negatively regulated osteoclast formation and did so via secreted, nonvesicular paracrine factors. Total RNA sequencing identified secreted factors overexpressed by PSCs which may explain their negative regulation of graft resorption. In summary, PSCs reduce osteoclast formation and prevent bone graft resorption in high turnover states such as gonadectomy-induced osteoporosis.
血管壁储存着间充质祖细胞，这些细胞能够通过直接和旁分泌机制诱导骨再生。尽管人们已经了解了血管周细胞对成骨细胞的调节作用，但它们对破骨细胞的调节作用以及在高骨吸收状态下的应用还不清楚。在这里，使用人血管周干细胞（PSCs）作为一种手段，在去势诱导的骨质疏松性脊柱融合模型中防止自体移植物吸收。此外，还通过共培养、条件培养基和纯化的细胞外囊泡评估了 PSCs 对破骨细胞形成的旁分泌调节作用。结果表明，当 PSCs 与自体骨混合时，会增加成骨细胞与破骨细胞的比例，促进骨基质的形成，并防止骨移植物的吸收。这些因素的融合导致去势大鼠腰椎融合模型中融合率很高。与未纯化的、培养定义的脂肪来源基质细胞或单独使用自体骨相比，PSCs 的应用在所有指标上都具有优越性。在共培养条件下，PSCs 负向调节破骨细胞的形成，这是通过分泌的、非囊泡旁分泌因子实现的。总 RNA 测序鉴定了 PSCs 过表达的分泌因子，这些因子可能解释了它们对移植物吸收的负调节作用。总之，PSCs 减少了高转换状态（如去势诱导的骨质疏松症）中成骨细胞的形成，并防止了骨移植物的吸收。
