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Abstract：
Cell transplantation is being actively explored as a regenerative therapy for discogenic back pain. This study explored the regenerative potential of Tie2+ nucleus pulposus progenitor cells (NPPCs) from intervertebral disc (IVD) tissues derived from young (<25 years of age) and old (>60 years of age) patient donors. We employed an optimized culture method to maintain Tie2 expression in NP cells from both donor categories. Our study revealed similar Tie2 positivity rates regardless of donor types following cell culture. Nevertheless, clear differences were also found, such as the emergence of significantly higher (3.6-fold) GD2 positivity and reduced (2.7-fold) proliferation potential for older donors compared to young sources. Our results suggest that, despite obtaining a high fraction of Tie2+ NP cells, cells from older donors were already committed to a more mature phenotype. These disparities translated into functional differences, influencing colony formation, extracellular matrix production, and in vivo regenerative potential. This study underscores the importance of considering age-related factors in NPPC-based therapies for disc degeneration. Further investigation into the genetic and epigenetic alterations of Tie2+ NP cells from older donors is crucial for refining regenerative strategies. These findings shed light on Tie2+ NPPCs as a promising cell source for IVD regeneration while emphasizing the need for comprehensive understanding and scalability considerations in culture methods for broader clinical applicability.
摘要：
正在积极探索细胞移植作为椎间盘源性背痛的再生疗法。这项研究探索了来自年轻（<25岁）和老年（>60岁）患者供体的椎间盘（IVD）组织的Tie2+髓核祖细胞（NPPC）的再生潜力。我们采用优化的培养方法来维持来自两个供体类别的NP细胞中的Tie2表达。我们的研究表明，无论细胞培养后的供体类型如何，Tie2阳性率相似。然而，还发现了明显的差异，例如，与年轻来源相比，老年供体的GD2阳性率显着提高（3.6倍），增殖潜力降低（2.7倍）。我们的研究结果表明,尽管获得了大量的Tie2+NP细胞，来自较老供体的细胞已经致力于更成熟的表型。这些差异转化为功能差异，影响菌落形成，细胞外基质的产生，和体内再生潜力。这项研究强调了在基于NPPC的椎间盘退变治疗中考虑年龄相关因素的重要性。进一步研究来自老年供体的Tie2+NP细胞的遗传和表观遗传改变对于完善再生策略至关重要。这些发现揭示了Tie2+NPPC作为IVD再生的有前途的细胞来源，同时强调了培养方法中全面理解和可扩展性的需要，以实现更广泛的临床适用性。
