Noggin-Loaded PLA/PCL Patch Inhibits BMP-Initiated Reactive Astrogliosis

Int J Mol Sci. 2024 Oct 29;25(21):11626. doi: 10.3390/ijms252111626.

Abstract

Myelomeningocele (MMC) is a congenital birth defect of the spine and spinal cord, commonly treated clinically through prenatal or postnatal surgery by repairing the unclosed spinal canal. Having previously developed a PLA/PCL polymer smart patch for this condition, we aim to further expand the potential therapeutic options by providing additional cellular and biochemical support in addition to its mechanical properties. Bone morphogenetic proteins (BMPs) are a large class of secreted factors that serve as modulators of development in multiple organ systems, including the CNS. We hypothesize that our smart patch mitigates the astrogenesis induced, at least partly, by increased BMP activity during MMC. To test this hypothesis, neural stem or precursor cells were isolated from rat fetuses and cultured in the presence of Noggin, an endogenous antagonist of BMP action, with recombinant BMPs. We found that the developed PLA/PCL patch not only serves as a biocompatible material for developing neural stem cells but was also able to act as a carrier for BMP-Notch pathway inhibitor Noggin, effectively minimizing the effect of BMP2 or BMP4 on NPCs cultured with the Noggin-loaded patch.

Keywords: PLA/PCL polymer smart patch; astrogliosis; myelomeningocele; neural precursor cells; noggin.

MeSH terms

  • Animals
  • Bone Morphogenetic Protein 2* / metabolism
  • Bone Morphogenetic Protein 4* / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Carrier Proteins* / metabolism
  • Cells, Cultured
  • Gliosis* / drug therapy
  • Gliosis* / metabolism
  • Gliosis* / pathology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Polyesters* / chemistry
  • Rats
  • Rats, Sprague-Dawley

Substances

  • noggin protein
  • Carrier Proteins
  • Polyesters
  • Bone Morphogenetic Protein 4
  • Bone Morphogenetic Protein 2
  • poly(lactide)
  • polycaprolactone
  • Bmp4 protein, rat
  • Bmp2 protein, rat
  • Bone Morphogenetic Proteins

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