A cocktail of growth factors released from a heparin hyaluronic-acid hydrogel promotes the myogenic potential of human urine-derived stem cells in vivo.
A cocktail of growth factors released from a heparin hyaluronic-acid hydrogel promotes the myogenic potential of human urine-derived stem cells in vivo.
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从肝素透明质酸水凝胶释放的生长因子混合物可促进体内人尿液干细胞的生肌潜力
DOI：
10.1016/j.actbio.2020.02.005
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发表时间：
2020-04-15
影响因子：
9.7
通讯作者：
Zhang Y
中科院分区：
文献类型：
--
作者：
Liu G;Wu R;Yang B;Shi Y;Deng C;Atala A;Mou S;Criswell T;Zhang Y
传统的细胞治疗技术依赖于体外原代干细胞的最大扩增，通过多次传代和潜在的分化方案，以便在体内移植之前产生所需的大量细胞。体外过度扩增和预分化细胞的植入通常导致细胞存活率差和体内组织修复的再生能力降低。我们假设，在体外短时间培养（传代次数≤p3）后，植入原代干细胞，结合相关生长因子的控释，将改善体内细胞活力、植入和组织再生。本研究的目的是确定从肝素-透明质酸凝胶（hp-HA凝胶）中释放的肌源性生长因子是否可以增强人尿源性干细胞（USC）的体内细胞存活、向内生长和肌源性分化，并相应增强移植物血管化、神经支配和再生特性。人USC获自健康成人供体（n = 6），扩增，然后与hp-HA凝胶混合，所述hp-HA凝胶含有已知增强肌生成（IGF 1、HGF、PDGF-BB）、神经生成（NGF、FGF）和血管生成（VEGF）的生长因子组，或具有生长因子组合的混合物。将与hp-HA凝胶和生长因子的各种组合混合的原代培养的USC（p3）皮下注射到无胸腺小鼠中。评估了宿主组织内的体内细胞存活、植入和功能分化。植入后4周，与其他组相比，含有USC和生长因子混合物的植入移植物显示出最大数量的存活细胞以及表达肌源性和内皮细胞标志物的细胞数量增加。此外，具有USC和生长因子鸡尾酒的移植物显示血管和浸润神经元的数量增加。因此，生长因子以受控的方式从含有USC的hp-HA凝胶中释放，有效地提高了体内细胞存活率，并支持移植物内的血管形成和肌源性分化。本研究提供了使用水凝胶中的原代USC和生长因子作为细胞治疗的新模式的证据，用于促进肌源性分化以治疗损伤的肌肉组织。
Traditional cell therapy technology relies on the maximum expansion of primary stem cells in vitro, through multiple passages and potential differentiation protocols, in order to generate the abundance of cells needed prior to transplantation in vivo. Implantation of in vitro over-expanded and pre-differentiated cells typically results in poor cell survival and reduced regeneration capacity for tissue repair in vivo. We hypothesized that implantation of primary stem cells, after a short time culture in vitro (passage number ≤p3), in combination with controlled release of relevant growth factors would improve in vivo cell viability, engraftment and tissue regeneration. The goal of this study was to determine whether the release of myogenic growth factors from a heparin-hyaluronic acid gel (hp-HA gel) could enhance in vivo cell survival, in-growth and myogenic differentiation of human urine-derived stem cells (USC) with a corresponding enhancement in graft vascularization, innervation and regenerative properties. Human USC were obtained from healthy adult donors (n = 6), expanded and then mixed with a hp-HA gel containing sets of growth factors known to enhance myogenesis (IGF1, HGF, PDGF-BB), neurogenesis (NGF, FGF) and angiogenesis (VEGF), or a cocktail with a combination of growth factors. Primary cultured USC (p3) mixed with the hp-HA gel and the various combinations of growth factors, were subcutaneously injected into athymic mice. In vivo cell survival, engraftment and functional differentiation within the host tissue were assessed. The implanted grafts containing USC and the growth factor cocktail showed the greatest number of surviving cells as well as increased numbers of cells that expressed myogenic and endothelial cell markers as compared to other groups 4 weeks after implantation. Moreover, the graft with USC and the growth factor cocktail showed increased numbers of blood vessels and infiltrating neurons. Thus, growth factors released in a controlled manner from an hp-HA gel containing USC efficiently improved in vivo cell survival and supported vascularization and myogenic differentiation within the grafts. This study provides evidence for the use of primary USC and growth factors in a hydrogel as a novel mode of cell therapy for the promotion of myogenic differentiation for the treatment of injured muscle tissue.
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影响因子：
2
作者：
Du, Xiao-Wen;Wu, Hui-Ling;Xu, Jian-Wei
通讯作者：
Xu, Jian-Wei
影响因子：
3.1
作者：
Liu, Libiao;Zhou, Xinwei;Wang, Xiaohong
通讯作者：
Wang, Xiaohong
人尿液干细胞分化为具有屏障功能和一氧化氮生成的内皮细胞
影响因子：
6
作者：
Liu G;Wu R;Yang B;Deng C;Lu X;Walker SJ;Ma PX;Mou S;Atala A;Zhang Y
通讯作者：
Zhang Y
DOI：
10.1016/j.bbrc.2014.01.084
发表时间：
2014-02-28
影响因子：
3.1
作者：
Eom, Young Woo;Oh, Ji-Eun;Shim, Kwang Yong
通讯作者：
Shim, Kwang Yong
影响因子：
4.1
作者：
Bharadwaj, Shantaram;Liu, Guihua;Zhang, Yuanyuan
通讯作者：
Zhang, Yuanyuan