Injection of Ultra-Purified Stem Cells with Sodium Alginate Reduces Discogenic Pain in a Rat Model

Cells. 2023 Feb 3;12(3):505. doi: 10.3390/cells12030505.

Abstract

Intervertebral disc (IVD) degeneration is a major cause of low back pain. However, treatments directly approaching the etiology of IVD degeneration and discogenic pain are not yet established. We previously demonstrated that intradiscal implantation of cell-free bioresorbable ultra-purified alginate (UPAL) gel promotes tissue repair and reduces discogenic pain, and a combination of ultra-purified, Good Manufacturing Practice (GMP)-compliant, human bone marrow mesenchymal stem cells (rapidly expanding clones; RECs), and the UPAL gel increasingly enhanced IVD regeneration in animal models. This study investigated the therapeutic efficacy of injecting a mixture of REC and UPAL non-gelling solution for discogenic pain and IVD regeneration in a rat caudal nucleus pulposus punch model. REC and UPAL mixture and UPAL alone suppressed not only the expression of TNF-α, IL-6, and TrkA (p < 0.01, respectively), but also IVD degeneration and nociceptive behavior compared to punching alone (p < 0.01, respectively). Furthermore, REC and UPAL mixture suppressed these expression levels and nociceptive behavior compared to UPAL alone (p < 0.01, respectively). These results suggest that this minimally invasive treatment strategy with a single injection may be applied to treat discogenic pain and as a regenerative therapy.

Keywords: intervertebral disc regeneration; low back pain; ultra-purified alginate; ultra-purified clonogenic bone marrow-derived mesenchymal stem cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / pharmacology
  • Animals
  • Humans
  • Intervertebral Disc Degeneration* / drug therapy
  • Intervertebral Disc Degeneration* / metabolism
  • Mesenchymal Stem Cells* / metabolism
  • Nucleus Pulposus*
  • Pain / drug therapy
  • Pain / metabolism
  • Rats

Substances

  • Alginates

Grants and funding

This research was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (20K17983 and 21H03313) and Project for Regenerative/Cellular Medicine and Gene Therapies at the Japan Agency for Medical Research and Development, AMED (JP22bk0104143h0001).