Combinated Transplantation of Neural Stem Cells and Collagen Type I Promote Functional Recovery After Cerebral Ischemia in Rats

Abstract

Using tissue engineering, a complex of neural stem cells (NSCs) and collagen type I was transplanted for the therapy of cerebral ischemic injury. NSCs from E14 d rats were dissociated and cultured by neurosphere formation in serum-free medium in the presence of basic fibroblast growth factor (bFGF), then seeded onto collagen to measure cell adhesive ability. BrdU was added to the culture medium to label the NSCs. Wistar rats (n=100) were subjected to 2-hour middle cerebral artery occlusion. After 24 hours of reperfusion, rats were assigned randomly to five groups: NSCs-collagen repair group, NSCs repair group, unseeded collagen repair group, MCAO medium group, and sham group. Neurological, immunohistological and electronic microscope assessments were performed to examine the effects of these treatments. Scanning electronic microscopy showed that NSCs assemble in the pores of collagen. At 3, 7, 15, and 30 d after transplantation of the NSC-collagen complex, some of the engrafted NSCs survive, differentiate and form synapses in the brains of rats subjected to cerebral ischemia. Six d after transplantation of the NSC-collagen complex into the brains of ischemic rats, the collagen began to degrade; 30 d after transplantation, the collagen had degraded completely. The implantation of NSCs and type I collagen facilitated the structural and functional recovery of neural tissue following ischemic injury. Anat Rec,

Biomaterials Application in Stem Cell Therapies for Stroke

“…There were only two studies that used cells with human origin [58,166]. Two studies used synthetic matrices [36,167], and the others applied natural scaffolds that were made from Matrigel [166], collagen [49,50], HA [14], or acellular tissue ECM [58]. All the experiments were performed in a middle cerebral artery occlusion model, except one that used cortical photothrombotic stroke [14].…”

“…They have been synthetized from either natural or synthetic materials (Table 13.2). Natural sources include proteins such as Matrigel [18], collagen [49,50], fibronectin [51], and fibrin [52], polysaccharides such as chitosan [53], agarose [54], alginate [55] and methylcellulose [56], hyaluronan (HA) [14,57] and acellular tissue matrix [58]. Many of these molecules are physiologically found in the extracellular matrix (ECM), and therefore their use has the advantage of promoting cell signaling through their binding sites for mammalian cells.…”

Stroke Repair via Biomimicry of the Subventricular Zone

“…NSCs assemble into the pores of the collagen matrix, where cells survive, differentiate, and re-build neural synapses in the MCAO rat model, displaying the start of collagen degradation after 6 days. Degradation processes facilitate the recovery of neural tissue post ischemia and allow for NSC integration to the host network (Yu et al, 2010). The incorporation of hyaluronan, heparin, and collagen into a hydrogel loaded with NSCs into a photo thrombotic stroke mouse model exhibits survival of the neural cells transplanted into the infarct cavity, a decrease in activated microglia and macrophage cells around the scaffold, and an increase in cell survival (Zhong et al, 2010).…”

Biomaterial applications in neural therapy and repair

“…Biomaterial scaffolds are natural or synthetic 3D polymer networks that provide an appropriate environment for cells to attach, proliferate, and differentiate to facilitate the formation of extracellular matrix (ECM) [46]. It is important to note that the chemical and mechanical properties of a biomaterial determine the fate of transplanted cells, as well as the drug release profile.…”

“…Collagen hydrogels have been used to encapsulate a variety of stem cell types for tissue engineering applications because of their biocompatibility, mechanical strength and immunogenicity [77]. In a rodent model of cerebral ischemia, encapsulation of NSCs in collagen type I hydrogel showed an increase in cell survival (compared to injection of cells alone), formation of synapsis, and facilitated the functional recovery of neural tissue following injury [46]. Another naturally occurring polysaccharide found in CNS and used for hydrogel formation is hyaluronan.…”