Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes.
Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes.
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DOI：
10.1007/s10544-014-9875-z
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发表时间：
2014-10
影响因子：
2.8
通讯作者：
Russell, Brenda
中科院分区：
文献类型：
--
作者：
Doroudian, Golnar;Pinney, James;Ayala, Perla;Los, Tamara;Desai, Tejal A.;Russell, Brenda
药物的局部释放对于组织修复可能具有许多优点，但也存在重大挑战。生物工程方法允许制造含有用于持续局部递送的生物活性肽的微结构。心脏组织损伤与IGF-1家族成员机械生长因子（MGF）的局部增加有关。MGF肽的E结构域是抗凋亡的和干细胞归巢因子。本研究的目的是制备载MGF多肽的聚乙二醇二甲基丙烯酸酯（PEGDMA）水凝胶微棒释放装置，并测定MGF的洗脱特性和生物活性。可注射微棒的硬度为30 kPa，宽度为15 μm，长度为100 μm，选择与心脏硬度和肌细胞大小相匹配的微棒。如通过HPLC测量的，通过2周的MGF递送实现了天然MGF肽在微棒内的成功包封。MGF微棒处理后，人骨髓间充质干细胞（hMSCs）的迁移能力增强（1.72±0.23，p<0.05）。缺氧8 h（1%O2）可抑制新生大鼠心室肌细胞凋亡途径。TUNEL法显示MGF微棒处理可抑制细胞凋亡，并增加Bcl-2表达（2±0.19，p<0.05）。无MGF的微棒调节hMSCs的细胞骨架、粘附和增殖，而MGF对这些特性没有影响。因此，组合微装置提供了机械提示和2周MGF生物活性以减少细胞凋亡和募集干细胞，表明MGF微棒在体内心脏再生治疗中的潜在用途。
Local release of drugs may have many advantages for tissue repair but also presents major challenges. Bioengineering approaches allow microstructures to be fabricated that contain bioactive peptides for sustained local delivery. Heart tissue damage is associated with local increases in mechano growth factor (MGF), a member of the IGF-1 family. The E domain of MGF peptide is anti-apoptotic and a stem cell homing factor. The objectives of this study were to fabricate a microrod delivery device of poly (ethylene glycol) dimethacrylate (PEGDMA) hydrogel loaded with MGF peptide and to determine the elution profile and bioactivity of MGF. The injectable microrods are 30 kPa stiffness and 15 μm widths by 100 μm lengths, chosen to match heart stiffness and myocyte size. Successful encapsulation of native MGF peptide within microrods was achieved with delivery of MGF for 2 weeks, as measured by HPLC. Migration of human mesenchymal stem cells (hMSCs) increased with MGF microrod treatment (1.72±0.23, p<0.05). Inhibition of the apoptotic pathway in neonatal rat ventricular myocytes was induced by 8 h of hypoxia (1 % O2). Protection from apoptosis by MGF microrod treatment was shown by the TUNEL assay and increased Bcl-2 expression (2±0.19, p<0.05). Microrods without MGF regulated the cytoskeleton, adhesion, and proliferation of hMSCs, and MGF had no effect on these properties. Therefore, the combination microdevice provided both the mechanical cues and 2-week MGF bioactivity to reduce apoptosis and recruit stem cells, suggesting potential use of MGF microrods for cardiac regeneration therapy in vivo.
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影响因子：
2.5
作者：
Biehl, Jesse K.;Yamanaka, Satoshi;Desai, Tejal A.;Boheler, Kenneth R.;Russell, Brenda
通讯作者：
Russell, Brenda
DOI：
10.1016/j.bbrc.2012.11.120
发表时间：
2013-01-18
影响因子：
3.1
作者：
Doroudian, Golnar;Curtis, Matthew W.;Gang, Anjulie;Russell, Brenda
通讯作者：
Russell, Brenda
影响因子：
--
作者：
Bray, Mark-Anthony;Sheehy, Sean P.;Parker, Kevin Kit
通讯作者：
Parker, Kevin Kit
影响因子：
4.5
作者：
Curtis, Matthew W.;Russell, Brenda
通讯作者：
Russell, Brenda
DOI：
10.1126/science.1171643
发表时间：
2009-06-26
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Discher DE;Mooney DJ;Zandstra PW
通讯作者：
Zandstra PW