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Remarkable migration propensity of dental pulp stem cells towards neurodegenerative milieu: An in vitro analysis.
NeuroToxicology ( IF 3.4 ) Pub Date : 2020-09-06 , DOI: 10.1016/j.neuro.2020.08.006
Sivapriya Senthilkumar 1 , Chaitra Venugopal 1 , Shagufta Parveen 1 , Shobha K 1 , Kiranmai S Rai 2 , Bindu M Kutty 3 , Anandh Dhanushkodi 1
Affiliation  

Stem cell therapy provides a ray of hope for treating neurodegenerative diseases (ND). Bone marrow mesenchymal stem cells (BM-MSC) were extensively investigated for their role in neuroregeneration. However, drawbacks like painful bone marrow extraction, less proliferation and poor CNS engraftment following systemic injections of BM-MSC prompt us to search for alternate/appropriate source of MSC for treating ND. In this context, dental pulp stem cells (DPSC) could be an alternative to BM-MSC as it possess both mesenchymal and neural characteristic features due to its origin from ectoderm, ease of isolation, higher proliferation index and better neuroprotection. A study on the migration potential of DPSC compared to BM-MSC in a neurodegenerative condition is warranted. Given the neural crest origin, we hypothesize that DPSC possess better migration towards neurodegenerative milieu as compared to BM-MSC. In this prospect, we investigated the migration potential of DPSC in an in vitro neurodegenerative condition. Towards this, transwell, Matrigel and chorioallantoic membrane (CAM) migration assays were carried-out by seeding hippocampal neurons in the lower chamber and treated with 300 μM kainic acid (KA) for 6 h to induce neurodegeneration. Subsequently, the upper chamber of transwell was loaded with DPSC/BM-MSC and their migration potential was assessed following 24 h of incubation. Our results revealed that the migration potential of DPSC/BM-MSC was comparable in non-degenerative condition. However, following injury the migration potential of DPSC towards the degenerating site was significantly higher as compared to BM-MSC. Furthermore, upon exposure of naïve DPSC/BM-MSCs to culture medium derived from neurodegenerative milieu resulted in significant upregulation of homing factors like SDF-1alpha, CXCR-4, VCAM-1, VLA-4, CD44, MMP-2 suggesting that the superior migration potential of DPSC might be due to prompt expression of homing factors in DPSC compared to BM-MSCs.



中文翻译:

牙髓干细胞向神经退行性环境的显着迁移倾向:体外分析。

干细胞疗法为治疗神经退行性疾病 (ND) 提供了一线希望。骨髓间充质干细胞 (BM-MSC) 在神经再生中的作用被广泛研究。然而,在全身注射 BM-MSC 后,骨髓提取疼痛、增殖较少和中枢神经系统植入不良等缺点促使我们寻找替代/合适的 MSC 来源来治疗 ND。在这种情况下,牙髓干细胞 (DPSC) 可以替代 BM-MSC,因为它来自外胚层,因此具有间充质和神经特征,易于分离,增殖指数更高,神经保护作用更好。有必要对 DPSC 与 BM-MSC 在神经退行性疾病中的迁移潜力进行研究。鉴于神经嵴起源,我们假设与 BM-MSC 相比,DPSC 具有更好的向神经退行性环境迁移的能力。在这个前景中,我们研究了 DPSC 在一个体外神经退行性疾病。为此,通过在下室接种海马神经元并用 300 μM 红藻氨酸 (KA) 处理 6 小时以诱导神经变性,进行 transwell、Matrigel 和绒毛膜尿囊膜 (CAM) 迁移测定。随后,transwell 的上室装有 DPSC/BM-MSC,并在孵育 24 小时后评估它们的迁移潜力。我们的结果表明 DPSC/BM-MSC 的迁移潜力在非退化条件下是可比的。然而,与 BM-MSC 相比,损伤后 DPSC 向退化部位的迁移潜力显着更高。此外,将初始 DPSC/BM-MSC 暴露于源自神经退行性环境的培养基后,导致归巢因子(如 SDF-1alpha、CXCR-4、VCAM-1、VLA-4、

更新日期:2020-09-20
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