Stem Cell Therapies for Intervertebral Disc Degeneration: Immune Privilege Reinforcement by Fas/FasL Regulating Machinery

被引:46
作者
Ma, Chi-Jiao [1 ]
Liu, Xu [1 ,2 ]
Che, Lu [1 ,2 ]
Liu, Zhi-Heng [3 ]
Samartzis, Dino [4 ]
Wang, Hai-Qiang [1 ]
机构
[1] Fourth Mil Med Univ, Dept Orthopaed, Xijing Hosp, Xian 710032, Peoples R China
[2] Fourth Mil Med Univ, Sch Aerosp Med, Xian 710032, Peoples R China
[3] Xian Air Force Hosp, Dept Orthopaed, Xian, Peoples R China
[4] Univ Hong Kong, Dept Orthopaed & Traumatol, Pokfulam, Hong Kong, Peoples R China
基金
中国国家自然科学基金;
关键词
Annulus fibrosus; Fas; FasL; immune privilege; immune response; intervertebral disc degeneration; nucleus pulposus; stem cells; NUCLEUS PULPOSUS CELLS; FAS-MEDIATED APOPTOSIS; LOW-BACK-PAIN; VERTEBRAL END-PLATE; HUMAN LUMBAR DISC; IN-VITRO; NOTOCHORDAL CELLS; EXTRACELLULAR-MATRIX; ORGAN-CULTURE; LIGAND EXPRESSION;
D O I
10.2174/1574888X10666150416114027
中图分类号
Q813 [细胞工程];
学科分类号
摘要
As a main contributing factor to low back pain, intervertebral disc degeneration (IDD) is the fundamental basis for various debilitating spinal diseases. The pros and cons of current treatment modalities necessitate biological treatment strategies targeting for reversing or altering the degeneration process in terms of molecules or genes. The advances in stem cell research facilitate the studies aiming for possible clinical application of stem cell therapies for IDD. Human NP cells are versatile with cell morphology full of variety, capable of synthesizing extracellular matrix components, engulfing substances by autophagy and phagocytosis, mitochondrial vacuolization indicating dysfunction, expressing Fas and FasL as significant omens of immune privileged sites. Human discs belong to immune privilege organs with functional FasL expression, which can interact with invasive immune cells by Fas-FasL regulatory machinery. IDD is characterized by decreased expression level of FasL with dysfunctional FasL, which in turn unbalances the interaction between NP cells and immune cells. Certain modulation factors might play a role in the process, such as miR-155. Accumulating evidence indicates that Fas-FasL network expresses in a variety of stem cells. Given the expression of functional FasL and insensitive Fas in stem cells (we term as FasL privilege), transplantation of stem cells into the disc may regenerate the degenerative disc by not only differentiating into NP-like cells, increasing extracellular matrix, but also reinforce immune privilege via interaction with immune cells by Fas-FasL network.
引用
收藏
页码:285 / 295
页数:11
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