The Journal of Spinal Cord Medicine ( IF 1.7 ) Pub Date : 2021-06-01 , DOI: 10.1080/10790268.2021.1930369 Krishnapriya Chandrababu 1 , Harikrishnan Vijayakumar Sreelatha 2 , Tara Sudhadevi 1 , Arya Anil 2 , Sabareeswaran Arumugam 3 , Lissy Kalliyana Krishnan 1
Background:
The multipotency of adipose-derived mesenchymal stem cells (ADMSC) could be an advantage to regenerate tissues with multiple cell types. However, due to the hostile nature, trauma sites like spinal cord injury can augment the ADMSC differentiation into undesirable lineages. Immersing pre-differentiated neural progenitors in a biomimetic niche during delivery could guard them against any undesired differentiation or death.
Objective:
The study proposes using an insoluble cell-specific fibrin niche for in vitro differentiation of rat ADMSCs to neural progenitor cells (NPCs) and oligodendrocyte progenitor cells (OPCs). Further, the study explores fibrin hydrogel for in vivo progenitor cell delivery, and that can aid post-transplant survival/differentiation.
Design:
The in vitro experiments analyzed for differentiation-specific markers to establish derivation of rADMSCs to rNPCs and rOPCs. The derived progenitors, tagged with fluorescent tracker dye were delivered in rat T10 contusion SCI using fibrin hydrogel. After 28 days, imaged the experiment site to determine cell survival, immunostained the tissues to identify differentiation of transplanted cells, and evaluated the effect of fibrin and cells on regulating the injury-associated immune response.
Results:
The study demonstrated fibrin niche aided stable differentiation of rat ADMSCs into neural progenitors. Fibrin matrix holds up the delivered progenitor cells in the SCI site. The H&E stained tissues revealed regulated cavitation, astrogliosis, and inflammation in test tissues. Progression of transplanted cells into oligodendrocytes upon delivering a mixture of rNPCs, rOPCs, and fibrin is evident.
Conclusion:
Fibrin niche-based derivation of neural progenitors from ADMSC seems valuable for transplantation using fibrin hydrogel. It is a promising strategy for extensive study towards further development of translational stem cell-based neural replacement therapy.
中文翻译:
使用脂肪来源的间充质干细胞和纤维蛋白基质进行体内神经组织工程
背景:
脂肪来源的间充质干细胞 (ADMSC) 的多能性可能是再生具有多种细胞类型的组织的优势。然而,由于敌对性质,脊髓损伤等创伤部位会增加 ADMSC 向不良谱系的分化。在分娩过程中将预分化的神经祖细胞浸入仿生生态位中可以防止它们发生任何不希望的分化或死亡。
客观的:
该研究建议使用不溶性细胞特异性纤维蛋白生态位将大鼠 ADMSCs体外分化为神经祖细胞 (NPC) 和少突胶质细胞祖细胞 (OPC)。此外,该研究探索了用于体内祖细胞递送的纤维蛋白水凝胶,这有助于移植后的存活/分化。
设计:
体外实验分析了分化特异性标记物,以建立 rADMSCs 到 rNPCs 和 rOPCs 的衍生。使用纤维蛋白水凝胶在大鼠 T10 挫伤 SCI 中递送用荧光跟踪染料标记的衍生祖细胞。28 天后,对实验部位进行成像以确定细胞存活率,对组织进行免疫染色以确定移植细胞的分化,并评估纤维蛋白和细胞对调节损伤相关免疫反应的影响。
结果:
该研究表明,纤维蛋白生态位有助于大鼠 ADMSC 稳定分化为神经祖细胞。纤维蛋白基质支撑着 SCI 部位输送的祖细胞。H&E 染色组织显示受控空化、星形胶质细胞增生和测试组织中的炎症。在递送 rNPC、rOPC 和纤维蛋白的混合物后,移植细胞进展为少突胶质细胞是显而易见的。
结论:
来自 ADMSC 的基于纤维蛋白生态位的神经祖细胞衍生似乎对使用纤维蛋白水凝胶进行移植很有价值。对于进一步开发基于转化干细胞的神经替代疗法的广泛研究,这是一个很有前途的策略。