Connecticut Convergence Institute for Translation in Regenerative Engineering, University of Connecticut Health, Farmington, Connecticut, USA.
Raymond and Beverly Sackler Center for Biomedical, Biological, Physical and Engineering Sciences, University of Connecticut Health, Farmington, Connecticut, USA.
Stem Cells Dev. 2022 Dec;31(23-24):787-798. doi: 10.1089/scd.2022.0053. Epub 2022 Sep 3.
Adipose-derived stem cells (ADSCs) hold tremendous potential for treating diseases and repairing damaged tissues. Heparan sulfate (HS) plays various roles in cellular signaling mechanisms. The importance of HS in stem cell function has been reported and well documented. However, there has been little progress in using HS for therapeutic purposes. We focused on one of the sulfotransferases, NDST1, which influences overall HS chain extent and sulfation pattern, with the expectation to enhance stem cell function by increasing the N-sulfation level. We herein performed transfections of a green fluorescent protein-vector control and NDST1-vector into mouse ADSCs to evaluate stem cell functions. Overexpression of NDST1 suppressed the osteogenic differentiation of ADSCs. There was no pronounced effect observed on the stemness, inflammatory gene expression, nor any noticeable effect in adipogenic and chondrogenic differentiation. Under the tumor necrosis factor-alpha stimulation, NDST1 overexpression induced several chemokine productions that attract neutrophils and macrophages. Finally, we identified an antifibrotic response in ADSCs overexpressing NDST1. This study provides a foundation for the evaluation of HS-related effects in ADSCs undergoing ex vivo gene manipulation.
脂肪干细胞 (ADSCs) 在治疗疾病和修复受损组织方面具有巨大潜力。硫酸乙酰肝素 (HS) 在细胞信号转导机制中发挥着多种作用。已有报道并充分证明了 HS 在干细胞功能中的重要性。然而，在治疗用途中使用 HS 的进展甚微。我们专注于其中一种硫酸转移酶 NDST1，它影响 HS 链的整体程度和硫酸化模式，期望通过增加 N-硫酸化水平来增强干细胞功能。我们在此通过转染绿色荧光蛋白载体对照和 NDST1 载体来评估小鼠 ADSCs 的干细胞功能。NDST1 的过表达抑制了 ADSCs 的成骨分化。然而，对干细胞特性、炎症基因表达，以及成脂和成软骨分化均没有明显影响。在肿瘤坏死因子-α刺激下，NDST1 的过表达诱导了几种趋化因子的产生，这些趋化因子吸引中性粒细胞和巨噬细胞。最后，我们在过表达 NDST1 的 ADSCs 中鉴定出一种抗纤维化反应。这项研究为评估 HS 相关效应在进行体外基因操作的 ADSCs 中的作用提供了基础。
