Nesti Leon J, Li Wan-Ju, Shanti Rabie M, Jiang Yi Jen, Jackson Wesley, Freedman Brett A, Kuklo Timothy R, Giuliani Jeffrey R, Tuan Rocky S
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA.
Tissue Eng Part A. 2008 Sep;14(9):1527-37. doi: 10.1089/ten.tea.2008.0215.
Degeneration of the intervertebral disc (IVD) represents a significant musculoskeletal disease burden. Although spinal fusion has some efficacy in pain management, spine biomechanics is ultimately compromised. In addition, there is inherent limitation of hardware-based IVD replacement prostheses, which underscores the importance of biological approaches to disc repair. In this study, we have seeded multipotent, adult human mesenchymal stem cells (MSCs) into a novel biomaterial amalgam to develop a biphasic construct that consisted of electrospun, biodegradable nanofibrous scaffold (NFS) enveloping a hyaluronic acid (HA) hydrogel center. The seeded MSCs were induced to undergo chondrogenesis in vitro in the presence of transforming growth factor-beta for up to 28 days. The cartilaginous hyaluronic acid-nanofibrous scaffold (HANFS) construct architecturally resembled a native IVD, with an outer annulus fibrosus-like region and inner nucleus pulposus-like region. Histological and biochemical analyses, immunohistochemistry, and gene expression profiling revealed the time-dependent development of chondrocytic phenotype of the seeded cells. The cells also maintain the microarchitecture of a native IVD. Taken together, these findings suggest the prototypic potential of MSC-seeded HANFS constructs for the tissue engineering of biological replacements of degenerated IVD.
椎间盘退变是一种严重的肌肉骨骼疾病负担。尽管脊柱融合术在疼痛管理方面有一定疗效,但脊柱生物力学最终会受到损害。此外,基于硬件的椎间盘置换假体存在固有限制,这凸显了生物方法修复椎间盘的重要性。在本研究中,我们将多能成人骨髓间充质干细胞(MSCs)接种到一种新型生物材料混合物中,以开发一种双相构建体,该构建体由包裹透明质酸(HA)水凝胶中心的电纺可生物降解纳米纤维支架(NFS)组成。在转化生长因子-β存在的情况下,接种的MSCs在体外被诱导进行软骨生成,长达28天。软骨样透明质酸-纳米纤维支架(HANFS)构建体在结构上类似于天然椎间盘,具有外层纤维环样区域和内层髓核样区域。组织学和生化分析、免疫组织化学和基因表达谱分析揭示了接种细胞软骨细胞表型的时间依赖性发展。这些细胞还维持了天然椎间盘的微观结构。综上所述,这些发现表明接种MSCs的HANFS构建体在组织工程化退变椎间盘生物替代物方面具有原型潜力。