A biomaterials approach to influence stem cell fate in injectable cell-based therapies.
A biomaterials approach to influence stem cell fate in injectable cell-based therapies.
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DOI：
10.1186/s13287-018-0789-1
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发表时间：
2018-02-21
影响因子：
7.5
通讯作者：
White LJ
中科院分区：
文献类型：
--
作者：
Amer MH;Rose FRAJ;Shakesheff KM;White LJ
许多干细胞疗法使用注射给药来提供高密度细胞制剂。然而，在移植后几天内观察到细胞保留率低至 1%。本研究研究了注射给药的不同给药方式和制剂参数对人间充质干细胞的细胞剂量恢复和分化命运选择的影响。研究了临床相关的汉密尔顿微型注射器和生物材料辅助输送对射血率的影响。评估细胞活力、作为活细胞递送的细胞剂量的百分比、增殖能力以及双电位培养基中的分化行为。还对基于生物材料的细胞载体进行了表征。观察到与天然生物材料共喷射的细胞的体外剂量恢复显着改善，喷射在 2% (w/v) 明胶范围内，导致 87.5±14% 的细胞剂量作为活细胞递送，而常用的盐水载体中以 10 µl/min 喷射的剂量为 32.2±19%。正如之前的研究表明的那样，细胞恢复的改善与所用生物材料的流变特性无关。尽管射血期间与细胞的接触时间有限，但成骨分化的程度显示出通过射血速率和细胞载体的选择而显着改变。相对于 PBS，I 型胶原蛋白和骨源性细胞外基质细胞载体在第 21 天沉积的矿化基质显着增加。加深对给药方案和生物材料如何影响细胞恢复、分化能力和命运选择的理解将有助于开发改进的给药和制剂方法，以实现干细胞移植的更高功效。本文的在线版本 (10.1186/s13287-018-0789-1) 包含补充材料，可供授权用户使用。
Numerous stem cell therapies use injection-based administration to deliver high-density cell preparations. However, cell retention rates as low as 1% have been observed within days of transplantation. This study investigated the effects of varying administration and formulation parameters of injection-based administration on cell dose recovery and differentiation fate choice of human mesenchymal stem cells. The impact of ejection rate via clinically relevant Hamilton micro-syringes and biomaterial-assisted delivery was investigated. Cell viability, the percentage of cell dose delivered as viable cells, proliferation capacity as well as differentiation behaviour in bipotential media were assessed. Characterisation of the biomaterial-based cell carriers was also carried out. A significant improvement of in-vitro dose recovery in cells co-ejected with natural biomaterials was observed, with ejections within 2% (w/v) gelatin resulting in 87.5 ± 14% of the cell dose being delivered as viable cells, compared to 32.2 ± 19% of the dose ejected in the commonly used saline vehicle at 10 μl/min. Improvement in cell recovery was not associated with the rheological properties of biomaterials utilised, as suggested by previous studies. The extent of osteogenic differentiation was shown to be substantially altered by choice of ejection rate and cell carrier, despite limited contact time with cells during ejection. Collagen type I and bone-derived extracellular matrix cell carriers yielded significant increases in mineralised matrix deposited at day 21 relative to PBS. An enhanced understanding of how administration protocols and biomaterials influence cell recovery, differentiation capacity and choice of fate will facilitate the development of improved administration and formulation approaches to achieve higher efficacy in stem cell transplantation. The online version of this article (10.1186/s13287-018-0789-1) contains supplementary material, which is available to authorized users.
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影响因子：
12.4
作者：
Chen Q;Shou P;Zheng C;Jiang M;Cao G;Yang Q;Cao J;Xie N;Velletri T;Zhang X;Xu C;Zhang L;Yang H;Hou J;Wang Y;Shi Y
通讯作者：
Shi Y
影响因子：
4.1
作者：
Dewitt, Daniel D.;Kaszuba, Stephanie N.;Stegemann, Jan P.
通讯作者：
Stegemann, Jan P.
DOI：
10.1016/0169-6009(92)90750-8
发表时间：
1992-05-01
期刊：
BONE AND MINERAL
影响因子：
--
作者：
GOLUB, EE;HARRISON, G;SHAPIRO, IM
通讯作者：
SHAPIRO, IM
影响因子：
--
作者：
Hoemann, C. D.;El-Gabalawy, H.;McKee, M. D.
通讯作者：
McKee, M. D.
影响因子：
3.7
作者：
ALTANKOV, G;GROTH, T
通讯作者：
GROTH, T