3B's Research Group, -Biomaterials, Biodegradables and Biomimetics, University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, AvePark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, Barco, Guimarães, Portugal.
ICVS/3B's - PT Government Associate Laboratory, Braga/Guimarães, Portugal.
J Cell Biochem. 2018 Apr;119(4):3653-3662. doi: 10.1002/jcb.26573. Epub 2018 Jan 11.
Poor clinical outcomes of tendon repair, together with limited regenerative capacity of the tissue, have triggered the search for alternative regenerative medicine strategies. Human adipose-derived stem cells (hASCs) are being investigated as a promising cell source in contributing for tendon repopulation and reconstruction. However, the mechanisms involved in a potential beneficial effect in tendon regeneration are still to be uncovered. To gain further insights on the bi-directional crosstalk occurring between stem cells and the native tendon niche, it was used an indirect (trans-well) system for co-culturing human tendon explants and hASCs. The maintenance of tissue architecture was studied up to 14 days by histological techniques. The secretion of MMPs was evaluated at day 3. The behavior of hASCs was assessed regarding cell elongation and extracellular matrix (ECM) production. The paracrine communication enhanced collagenolytic activity of MMPs in co-cultures at day 3, in comparison to hASCs alone or tendon explants alone, suggesting that ECM remodeling is triggered early in culture. Moreover, hASCs were spontaneously more elongated in co-cultures and the deposition of collagen type III and tenascin-C by hASCs in co-culture was observed at a lower extent after 7 days, in comparison to hASCs alone, being lately recovered at day 14. Overall, explant co-cultures established herein may constitute a tool for replicating the first steps in tendon healing and help uncovering the bi-directional communication occurring between hASCs and the native tendon niche.
肌腱修复的临床效果不佳，加上组织的再生能力有限，这促使人们寻求替代的再生医学策略。人脂肪来源干细胞（hASCs）作为一种有前途的细胞来源，正在被研究用于肌腱再填充和重建。然而，在肌腱再生中发挥潜在有益作用的机制仍有待揭示。为了进一步了解干细胞与天然肌腱微环境之间发生的双向串扰，采用间接（Trans-well）共培养系统来共培养人肌腱外植体和 hASCs。通过组织学技术研究组织形态维持至第 14 天。在第 3 天评估 MMPs 的分泌情况。评估 hASCs 的行为，包括细胞伸长和细胞外基质（ECM）的产生。与单独的 hASCs 或单独的肌腱外植体相比，共培养物中 MMPs 的胶原酶活性在第 3 天增强，表明 ECM 重塑在培养早期就被触发。此外，hASCs 在共培养中自发伸长更多，并且在第 7 天观察到 hASCs 在共培养中的 III 型胶原和腱糖蛋白 C 的沉积程度较低，而在第 14 天则恢复。总体而言，本文建立的外植体共培养物可能成为复制肌腱愈合早期步骤的工具，并有助于揭示 hASCs 与天然肌腱微环境之间发生的双向通讯。
