Reprogramming to restore youthful epigenetics of senescent nucleus pulposus cells for mitigating intervertebral disc degeneration and alleviating low back pain.

Wenzheng Ma, Wantao Wang, Lei Zhao, Jinghao Fan, Lei Liu, Lin Huang, Baogan Peng, Jianru Wang, Baoshan Xu, Hongmei Liu, Decheng Wu, Zhaomin Zheng

Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.Department of Spine Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. · pubmed

Paper

Abstract

Aging is a pivotal risk factor for intervertebral disc degeneration (IVDD) and chronic low back pain (LBP). The restoration of aging nucleus pulposus cells (NPCs) to a youthful epigenetic state is crucial for IVDD treatment, but remains a formidable challenge. Here, we proposed a strategy to partially reprogram and reinstate youthful epigenetics of senescent NPCs by delivering a plasmid carrier that expressed pluripotency-associated genes (Oct4, Klf4 and Sox2) in Cavin2-modified exosomes (OKS@M-Exo) for treatment of IVDD and alleviating LBP. The functional OKS@M-Exo efficaciously alleviated senescence markers (p16

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Research summary

The paper claims that delivering a plasmid carrier expressing pluripotency-associated genes can restore youthful epigenetics in senescent nucleus pulposus cells to mitigate intervertebral disc degeneration. This research addresses the underlying mechanisms of aging by attempting to reverse cellular senescence, which is a key factor in age-related degeneration and pain, thus contributing to the field of longevity.

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