Dental and Craniofacial Research Institute, University of California, Los Angeles, USA. 900950-1579, USA.
Stem Cells Transl Med. 2012 Jun;1(6):510-9. doi: 10.5966/sctm.2012-0002. Epub 2012 Jun 11.
Adipose tissue is an ideal source of mesenchymal stem cells for bone tissue engineering: it is largely dispensable and readily accessible with minimal morbidity. However, the stromal vascular fraction (SVF) of adipose tissue is a heterogeneous cell population, which leads to unreliable bone formation. In the present study, we prospectively purified human perivascular stem cells (PSCs) from adipose tissue and compared their bone-forming capacity with that of traditionally derived SVF. PSCs are a population (sorted by fluorescence-activated cell sorting) of pericytes (CD146+CD34-CD45-) and adventitial cells (CD146-CD34+CD45-), each of which we have previously reported to have properties of mesenchymal stem cells. Here, we found that PSCs underwent osteogenic differentiation in vitro and formed bone after intramuscular implantation without the need for predifferentiation. We next sought to optimize PSCs for in vivo bone formation, adopting a demineralized bone matrix for osteoinduction and tricalcium phosphate particle formulation for protein release. Patient-matched, purified PSCs formed significantly more bone in comparison with traditionally derived SVF by all parameters. Recombinant bone morphogenetic protein 2 increased in vivo bone formation but with a massive adipogenic response. In contrast, recombinant Nel-like molecule 1 (NELL-1; a novel osteoinductive growth factor) selectively enhanced bone formation. These studies suggest that adipose-derived human PSCs are a new cell source for future efforts in skeletal regenerative medicine. Moreover, PSCs are a stem cell-based therapeutic that is readily approvable by the U.S. Food and Drug Administration, with potentially increased safety, purity, identity, potency, and efficacy. Finally, NELL-1 is a candidate growth factor able to induce human PSC osteogenesis.
它具有很大的可替代性，并且可以通过最小的发病率轻松获得。然而，脂肪组织的基质血管部分（SVF）是一种异质细胞群体，这导致骨形成不可靠。在本研究中，我们前瞻性地从脂肪组织中纯化了人血管周干细胞（PSCs），并比较了它们的成骨能力与传统 SVF 的成骨能力。PSCs 是一个群体（通过荧光激活细胞分选进行分选），包括周细胞（CD146+CD34-CD45-）和外膜细胞（CD146-CD34+CD45-），我们之前曾报道过这两种细胞都具有间充质干细胞的特性。在这里，我们发现 PSCs 可以在体外进行成骨分化，并在肌肉内植入后形成骨，而无需预先分化。接下来，我们试图通过采用脱钙骨基质进行骨诱导和三钙磷酸盐颗粒制剂进行蛋白释放来优化 PSCs 的体内成骨作用。与传统的 SVF 相比，患者匹配的、纯化的 PSCs 通过所有参数形成的骨量明显更多。重组骨形态发生蛋白 2（BMP-2）增加了体内骨形成，但伴随着大量的成脂反应。相比之下，重组类似神经细胞外调节蛋白 1（NELL-1；一种新的成骨诱导生长因子）选择性地增强了骨形成。这些研究表明，脂肪来源的人 PSCs 是未来骨骼再生医学努力的新细胞来源。此外，PSCs 是一种基于干细胞的治疗方法，很容易获得美国食品和药物管理局的批准，具有潜在的更高安全性、纯度、身份、效力和疗效。最后，NELL-1 是一种能够诱导人 PSC 成骨的候选生长因子。
