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载有 Noggin 的 PLA/PCL 贴片抑制 BMP 引发的反应性星形胶质细胞增生。

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

机构信息

Center for Fetal and Placental Research, Cincinnati Children's Hospital Medical Center (CCHMC), Cincinnati, OH 45229, USA.

Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH 45219, USA.

出版信息

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

DOI:10.3390/ijms252111626
PMID:39519177
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11545872/
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.

摘要

脊髓脊膜膨出（MMC）是一种先天性脊柱和脊髓畸形，临床上通常通过产前或产后手术来修复未闭合的椎管进行治疗。我们先前已经为这种疾病开发了 PLA/PCL 聚合物智能贴片，旨在通过提供额外的细胞和生化支持来进一步扩展其潜在的治疗选择，除了其机械性能之外。骨形态发生蛋白（BMPs）是一大类分泌因子，作为包括中枢神经系统在内的多个器官系统发育的调节剂。我们假设我们的智能贴片至少部分缓解了由 MMC 期间 BMP 活性增加引起的星形胶质细胞发生。为了验证这一假设，我们从大鼠胎盘中分离出神经干细胞或前体细胞，并在 Noggin（BMP 作用的内源性拮抗剂）存在的情况下进行培养，Noggin 与重组 BMPs 一起使用。我们发现，开发的 PLA/PCL 贴片不仅是一种用于培养神经干细胞的生物相容性材料，而且还能够作为 BMP-Notch 通路抑制剂 Noggin 的载体，有效地将 BMP2 或 BMP4 对用 Noggin 加载贴片培养的 NPC 的影响降到最低。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/a9c636addd80/ijms-25-11626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/cc777784969c/ijms-25-11626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/f6592c95413d/ijms-25-11626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/1ab2bebabd9e/ijms-25-11626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/d8347efaf285/ijms-25-11626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/a9c636addd80/ijms-25-11626-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/cc777784969c/ijms-25-11626-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/f6592c95413d/ijms-25-11626-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/1ab2bebabd9e/ijms-25-11626-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/d8347efaf285/ijms-25-11626-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a690/11545872/a9c636addd80/ijms-25-11626-g005.jpg

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