Department of Orthopaedics & Traumatology, The University of Hong Kong, Hong Kong SAR, People's Republic of China; Department of Biochemistry, The University of Hong Kong, Hong Kong SAR, People's Republic of China; Centre for Reproduction, Development, and Growth, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Stem Cells. 2014 Aug;32(8):2164-77. doi: 10.1002/stem.1717.
Intervertebral disc degeneration is associated with back pain and radiculopathy which, being a leading cause of disability, seriously affects the quality of life and presents a hefty burden to society. There is no effective intervention for the disease and the etiology remains unclear. Here, we show that disc degeneration exhibits features of fibrosis in humans and confirmed this in a puncture-induced disc degeneration (PDD) model in rabbit. Implantation of bone marrow-derived mesenchymal stem cells (MSCs) to PDD discs can inhibit fibrosis in the nucleus pulposus with effective preservation of mechanical properties and overall spinal function. We showed that the presence of MSCs can suppress abnormal deposition of collagen I in the nucleus pulposus, modulating profibrotic mediators MMP12 and HSP47, thus reducing collagen aggregation and maintaining proper fibrillar properties and function. As collagen fibrils can regulate progenitor cell activities, our finding provides new insight to the limited self-repair capability of the intervertebral disc and importantly the mechanism by which MSCs may potentiate tissue regeneration through regulating collagen fibrillogenesis in the context of fibrotic diseases.
椎间盘退变与腰痛和神经根病有关，后者是导致残疾的主要原因，严重影响生活质量，并给社会带来沉重负担。目前尚无针对该疾病的有效干预措施，其病因仍不清楚。在这里，我们发现人类椎间盘退变具有纤维化特征，并在兔椎间盘穿刺诱导退变（PDD）模型中得到证实。将骨髓间充质干细胞（MSCs）植入 PDD 椎间盘可抑制髓核纤维化，有效保持力学性能和整体脊柱功能。我们发现 MSC 的存在可以抑制椎间盘髓核中胶原 I 的异常沉积，调节致纤维化介质 MMP12 和 HSP47，从而减少胶原聚集，保持适当的纤维状特性和功能。由于胶原纤维可以调节祖细胞的活性，我们的发现为椎间盘的自我修复能力有限提供了新的见解，并且重要的是，MSC 可能通过调节纤维化疾病中胶原原纤维形成来增强组织再生的机制。
