Tunable, Injectable Hydrogels Based on Peptide-Cross-Linked, Cyclized Polymer Nanoparticles for Neural Progenitor Cell Delivery

2017 ◽  
Vol 18 (9) ◽  
pp. 2723-2731 ◽  
Author(s):  
Tianyu Zhao ◽  
Drew L. Sellers ◽  
Yilong Cheng ◽  
Philip J. Horner ◽  
Suzie H. Pun
Author(s):  
Tara Sudhadevi ◽  
Harikrishnan Vijayakumar Sreelatha ◽  
Easwer V Hariharan ◽  
Samavedam Sandhyamani ◽  
Lissy K Krishnan

Abstract Transplantation of neural progenitor cell (NPC) possessing the potential to differentiate into neurons may guard against spinal cord injury (SCI)- associated neuronal trauma. We propose that autologous-like NPC may reduce post-transplant immune response. The study used the rat SCI model to prove this concept. For isolation and expansion of rat NPC for cell-based SCI therapy, the in vitro protocol standardized with human NPC seemed suitable. The primary aim of this study is to select a cell/neural tissue-compatible biomaterial for improving NPC survival in vivo. The composition of the fibrin hydrogel is adjusted to obtain degradable, porous, and robust fibrin strands for supporting neural cell attachment, migration, and tissue regeneration. This study employed NPC culture to evaluate the cytocompatibility and suitability of the hydrogel, composed by adding graded concentrations of thrombin to a fixed fibrinogen concentration. The microstructure evaluation by scanning electron microscope guided the selection of a suitable composition for delivering the embedded cells. On adding more thrombin, fibrinogen clotted quickly but reduced porosity, pore size, and fiber strand thickness. The high activity of thrombin also affected NPC morphology and the in vitro cell survival. The selected hydrogel carried viable NPC and retained them at the injury site post-transplantation. The fibrin hydrogel played a protective role throughout the transfer process by providing cell attachment sites and survival signals. The fibrin and NPC together regulated the immune response at the SCI site reducing ED1+ve/ED2+ve macrophages in the early period of 8 to 16 days after injury. Migration of β-III tubulin+ve neural-like cells into the fibrin-injected control SCI is evident. The continuous use of a non-neurotoxic fibrin matrix could be a convenient strategy for in vitro NPC preparation, minimally invasive cell delivery, and better transplantation outcome.


2017 ◽  
Vol 216 (7) ◽  
pp. 1975-1992 ◽  
Author(s):  
Yanxin Li ◽  
Jianwei Jiao

Histone cell cycle regulator (HIRA) is a histone chaperone and has been identified as an epigenetic regulator. Subsequent studies have provided evidence that HIRA plays key roles in embryonic development, but its function during early neurogenesis remains unknown. Here, we demonstrate that HIRA is enriched in neural progenitor cells, and HIRA knockdown reduces neural progenitor cell proliferation, increases terminal mitosis and cell cycle exit, and ultimately results in premature neuronal differentiation. Additionally, we demonstrate that HIRA enhances β-catenin expression by recruiting H3K4 trimethyltransferase Setd1A, which increases H3K4me3 levels and heightens the promoter activity of β-catenin. Significantly, overexpression of HIRA, HIRA N-terminal domain, or β-catenin can override neurogenesis abnormities caused by HIRA defects. Collectively, these data implicate that HIRA, cooperating with Setd1A, modulates β-catenin expression and then regulates neurogenesis. This finding represents a novel epigenetic mechanism underlying the histone code and has profound and lasting implications for diseases and neurobiology.


RSC Advances ◽  
2017 ◽  
Vol 7 (72) ◽  
pp. 45587-45594 ◽  
Author(s):  
Lingyan Yang ◽  
Ziyun Jiang ◽  
Linhong Zhou ◽  
Keli Zhao ◽  
Xun Ma ◽  
...  

Cell-derived extracellular matrix exhibits excellent adhesion performance for neural progenitor cell anchoring and residency, resulting in promoted proliferation of the stem cells to basal forebrain cholinergic neurons.


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