Human dental pulp stem cells exhibit enhanced properties in comparison to human bone marrow stem cells on neurites outgrowth
Human dental pulp stem cells exhibit enhanced properties in comparison to human bone marrow stem cells on neurites outgrowth
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DOI：
10.1096/fj.201902482r
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发表时间：
2020-02-25
期刊：
影响因子：
4.8
通讯作者：
Mitsiadis, Thimios A.
中科院分区：
文献类型：
--
作者：
Pagella, Pierfrancesco;Miran, Shayee;Mitsiadis, Thimios A.
间充质干细胞具有自我更新和分化为特定细胞类型的能力，因此是组织修复和再生的关键角色。骨髓间充质干细胞用于体内组织再生的研究越来越多，并且已经构成了现有临床治疗的一种有前途的替代方案。MSCs还发挥旁分泌和营养功能，包括促进神经支配，在再生和器官功能恢复中发挥基础作用。人骨髓干细胞(HBMSCs)和人牙髓干细胞(HDPSCs)已被用于修复和/或再生颅面复合体的骨或其他组织的研究。然而，hBMSCs和hDPSCs诱导特定轴突生长以重建愈合组织的功能性神经的能力尚不清楚。在这里，我们利用微流控芯片器官设备比较了hDPSCs和hBMSCs对三叉神经节和背根节神经元的神经营养作用。我们发现hDPSCs表达的神经营养因子水平明显高于hBMSCs，因此，与hDPSCs共培养的神经元在微流控共培养系统中比与hBMSCs共培养的神经元发育出更长的轴突。此外，hDPSCs诱导形成广泛的轴突网络，并与神经元建立密切联系，这是在hBMSCs存在下没有观察到的现象。综上所述，这些发现表明，hDPSC是恢复受损头面部组织功能的更好选择，因为它们能够支持和促进广泛的三叉神经支配。
Mesenchymal stem cells (MSCs) have the capacity to self-renew and differentiate into specific cell types and are, therefore, key players during tissue repair and regeneration. The use of MSCs for the regeneration of tissues in vivo is increasingly being explored and already constitutes a promising alternative to existing clinical treatments. MSCs also exert paracrine and trophic functions, including the promotion of innervation that plays fundamental roles in regeneration and in restoration of the function of organs. Human bone marrow stem cells (hBMSCs) and human dental pulp stem cells (hDPSCs) have been used in studies that aimed at the repair and/or regeneration of bone or other tissues of the craniofacial complex. However, the capabilities of hBMSCs and hDPSCs to elicit the growth of specific axons in order to reestablish functional innervation of the healing tissues are not known. Here, we compared the neurotrophic effects of hDPSCs and hBMSCs on trigeminal and dorsal root ganglia neurons using microfluidic organs-on-chips devices. We found that hDPSCs express significantly higher levels of neurotrophins than hBMSCs and consequently neurons cocultured with hDPSCs develop longer axons in the microfluidic co-culture system when compared to neurons cocultured with hBMSCs. Moreover, hDPSCs elicited the formation of extensive axonal networks and established close contacts with neurons, a phenomenon not observed in presence of hBMSCs. Taken together, these findings indicate that hDPSCs constitute a superior option for restoring the functionality of damaged craniofacial tissues, as they are able to support and promote extensive trigeminal innervation.