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Stem Cell-derived Exosomes – A New Therapeutic Option for a Common Cause of Back Pain?

Review of Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagyfrom STEM CELLS by Stuart P. Atkinson

A reduction in the number of functional nucleus pulposus cells of the intervertebral disc thanks to a lack of adequate nutrient supply from the surrounding cartilage endplates [1] represents one of the major characteristics of intervertebral disc degeneration, a common cause of lower back pain that limits activity [2]. While cartilage endplate stem cells (CESCs) inhibit intervertebral disc degeneration by promoting nucleus pulposus cell regeneration and regulating intervertebral disc homeostasis [3-5], the controlling mechanism remains unclear.

A recent study from researchers led by MingHan Liu, Yue Zhou, and Zhiqiang Tian (Army Medical University, Chongqing, China) sought to gain mechanistic insight into the development of intervertebral disc degeneration by exploring a potential role for CESC‐derived exosomes and their ability to modulate autophagic flux [6]. In their new STEM CELLS article [7], Luo et al. now describe how exosomes derived from healthy CESCs may represent an exciting therapeutic approach to the prevention of intervertebral disc degeneration and the onset of lower back pain.

The authors first evaluated the responses of rat nucleus pulposus cells following treatment with exosomes derived from healthy and degenerated rat CESCs (induced by tert‐butyl hydroperoxide-mediated inflammation), finding that healthy CESC exosomes had a significantly greater ability to inhibit nucleus pulposus cell apoptosis. Interestingly, the improved therapeutic capacity of healthy CESC exosomes derived from their ability to activate autophagic flux via the PI3K/AKT pathway, as evidenced by experiments using the AKT inhibitor LY294002. In contrast, exosomes derived from degenerated CESCs failed to induce PI3K/AKT pathway or autophagic flux to a similar level, which correlated with an increase in nucleus pulposus cell apoptosis.

Subsequent in vivo analyses in a rat tail model of intervertebral disc degeneration (again induced by inflammation) also demonstrated the significantly greater ability of healthy CESC exosomes to inhibit nucleus pulposus cell apoptosis and attenuate intervertebral disc degeneration by activating the PI3K/AKT/autophagy signaling pathway. Therefore, exosomes, or components contained within exosomes, may represent an efficient, cell-free means to treat or prevent the common causes of lower back pain.

For more on how stem cell-derived exosomes may represent an effective treatment for the causes of lower back pain, stay tuned to the Stem Cells Portal!

References

  1. Wong J, Sampson SL, Bell-Briones H, et al., Nutrient supply and nucleus pulposus cell function: effects of the transport properties of the cartilage endplate and potential implications for intradiscal biologic therapy. Osteoarthritis and Cartilage 2019;27:956-964.
  2. Andersson GBJ, Epidemiological features of chronic low-back pain. The Lancet 1999;354:581-585.
  3. Wang H, Zhou Y, Huang B, et al., Utilization of Stem Cells in Alginate for Nucleus Pulposus Tissue Engineering. Tissue Engineering Part A 2013;20:908-920.
  4. Chen S, Zhao L, Deng X, et al., Mesenchymal Stem Cells Protect Nucleus Pulposus Cells from Compression-Induced Apoptosis by Inhibiting the Mitochondrial Pathway. Stem Cells International 2017;2017:9843120.
  5. Wang W, Wang Y, Deng G, et al., Transplantation of Hypoxic-Preconditioned Bone Mesenchymal Stem Cells Retards Intervertebral Disc Degeneration via Enhancing Implanted Cell Survival and Migration in Rats. Stem Cells International 2018;2018:7564159.
  6. Liu H, Sun X, Gong X, et al., Human umbilical cord mesenchymal stem cells derived exosomes exert antiapoptosis effect via activating PI3K/Akt/mTOR pathway on H9C2 cells. Journal of Cellular Biochemistry 2019;120:14455-14464.
  7. Luo L, Jian X, Sun H, et al., Cartilage endplate stem cells inhibit intervertebral disc degeneration by releasing exosomes to nucleus pulposus cells to activate Akt/autophagy. STEM CELLS 2021;39:467-481.