Transient exposure to TGF-β3 improves the functional chondrogenesis of MSC-laden hyaluronic acid hydrogels.
Transient exposure to TGF-β3 improves the functional chondrogenesis of MSC-laden hyaluronic acid hydrogels.
复制标题
短暂暴露于 TGF-β3 可改善装载 MSC 的透明质酸水凝胶的功能性软骨形成。
DOI：
10.1016/j.jmbbm.2012.03.006
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发表时间：
2012-07
影响因子：
3.9
通讯作者：
Mauck RL
中科院分区：
文献类型：
--
作者：
Kim M;Erickson IE;Choudhury M;Pleshko N;Mauck RL
利用成体干细胞进行组织工程是修复关节软骨局灶性缺损的一种很有前途的方法。为此，祖细胞将理想地经由生物相容性材料并与可溶性因子组合递送到缺损部位（并维持在缺损部位内），以促进初始细胞分化和随后的体内组织成熟。虽然生长因子递送方法不断被优化，但大多数在高剂量下仅提供短（数天至数周）递送曲线。为了解决这个问题，我们研究了间充质干细胞（MSC）在光交联透明质酸（HA）水凝胶中的分化和成熟，并短暂暴露于促软骨形成分子转化生长因子-β 3（TGF-β3），剂量（10，50和100 ng/mL）和持续时间（3，7，21和63天）。通过9周的培养评价机械、生化和组织学结果。结果显示，短暂暴露（7天）于非常高水平（100 ng/mL）的TGF-β 3足以诱导和维持这些3D构建体中的软骨形成。事实上，这种短时间递送导致构建体的机械和生物化学性质超过在整个9周时间过程中连续暴露于较低水平（10 ng/mL）的TGF-β 3的机械和生物化学性质。值得注意的是，这两种情况下的总TGF递送大致相等（200 ng对180 ng），但递送时间明显不同。这些数据支持这样的观点，即急性暴露于高剂量的TGF将诱导干细胞群的功能性和长期分化，并进一步促进我们在体内改善软骨修复的努力。
Tissue engineering with adult stem cells is a promising approach for the restoration of focal defects in articular cartilage. For this, progenitor cells would ideally be delivered to (and maintained within) the defect site via a biocompatible material and in combination with soluble factors to promote initial cell differentiation and subsequent tissue maturation in vivo. While growth factor delivery methods are continually being optimized, most offer only a short (days to weeks) delivery profile at high doses. To address this issue, we investigated mesenchymal stem cell (MSC) differentiation and maturation in photocrosslinkable hyaluronic acid (HA) hydrogels with transient exposure to the pro-chondrogenic molecule transforming growth factor-beta3 (TGF-β3), at varying doses (10, 50 and 100 ng/mL) and durations (3, 7, 21 and 63 days). Mechanical, biochemical, and histological outcomes were evaluated through 9 weeks of culture. Results showed that a brief exposure (7 days) to a very high level (100 ng/mL) of TGF-β 3 was sufficient to both induce and maintain cartilage formation in these 3D constructs. Indeed, this short delivery resulted in constructs with mechanical and biochemical properties that exceeded that of continuous exposure to a lower level (10 ng/mL) of TGF-β 3 over the entire 9-week time course. Of important note, the total TGF delivery in these two scenarios was roughly equivalent (200 vs. 180 ng), but the timing of delivery differed markedly. These data support the idea that acute exposure to a high dose of TGF will induce functional and long-term differentiation of stem cell populations, and furthers our efforts to improve cartilage repair in vivo.