Division of Neurosurgery, City of Hope Cancer Center, Los Angeles, California, USA.
Adv Exp Med Biol. 2012;760:188-210. doi: 10.1007/978-1-4614-4090-1_12.
Advancement of in vitro osteogenesis, or the production of bone, is a complex process that has significant clinical implications. Surgical intervention of several spinal disorders entails decompression of the spinal cord and nerves which can lead to subsequent biomechanical instability of the spine. Spinal arthrodesis (fusion) is often required to correct this instability and necessary to eliminate the resulting pathological motion of vertebral segments. Therefore, the achievement of proper spinal fusion, is a critical determinant of treatment efficacy. This chapter focuses on the molecular and cellular components that are involved in bone growth and healing. Mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) are the precursor cells essential for the formation of the five different types of bone cells: osteoprogenitor cells, osteoblasts, osteoclasts, osteocytes and lining cells. Similarly, endothelial progenitor cells (EPCs) differentiate into endothelial cells, which are essential in angiogenesis and neovascularization. MSCs tri-lineage potential (osteogenic, chondrogenic and adipogenic lineages) have made them the focus of most experimental approaches. Here, we describe their individual roles, as well as pose novel concepts on how their collective role may be the optimal strategy to improve upon in vitro osteogenesis and whether this could also be translated to improved bone formation in vivo. Further, we discuss the various molecular markers that are available for cell identification and the tissue engineering strategies that could replicate the osteoinductive, osteoconductive and osteoproductive milieuthat is available in autograft. Finally, we present a broad primer on the possible integration of cellular, molecular and tissue engineering strategies to improve osteogenesis and the future trends that may bring the promise seen in the laboratory to fruition in preclinical animal models.
体外成骨,即骨的生成,是一个复杂的过程,具有重要的临床意义。几种脊柱疾病的手术干预需要对脊髓和神经进行减压,这可能导致脊柱随后出现生物力学不稳定。为了纠正这种不稳定性,通常需要进行脊柱关节融合术(融合),以消除椎体节段的病理性运动。因此,实现适当的脊柱融合是治疗效果的关键决定因素。本章重点介绍与骨骼生长和愈合相关的分子和细胞成分。间充质干细胞(MSCs)和造血干细胞(HSCs)是形成五种不同类型骨细胞所必需的前体细胞:成骨前体细胞、成骨细胞、破骨细胞、骨细胞和衬里细胞。同样,内皮祖细胞(EPCs)分化为内皮细胞,对于血管生成和新血管生成至关重要。MSCs 的三系潜能(成骨、成软骨和成脂谱系)使它们成为大多数实验方法的焦点。在这里,我们描述了它们各自的作用,并提出了新概念,即它们的集体作用如何可能是改善体外成骨的最佳策略,以及这是否也可以转化为改善体内骨形成。此外,我们还讨论了可用于细胞鉴定的各种分子标记以及可复制自体移植物中存在的诱导成骨、成骨和促进骨生成环境的组织工程策略。最后,我们广泛介绍了细胞、分子和组织工程策略的可能整合,以改善成骨,并探讨可能将实验室中看到的前景转化为临床前动物模型中的成果的未来趋势。