Laminin and fibronectin scaffolds enhance neural stem cell transplantation into the injured brain

Abstract

Cell transplantation offers the potential to treat central nervous system injuries, largely because multiple mechanisms can be targeted in a sustained fashion. It is crucial that cells are transplanted into an environment that is favourable for extended survival and integration within the host tissue. Given the success of using fetal tissue grafts for traumatic brain injury, it may be beneficial to mimic key aspects of these grafts (e.g. three-dimensionality, cell-cell and cell-matrix support) to deliver cells. Extracellular matrix proteins such as fibronectin and laminin are involved in neural development and may provide adhesive support for donor cells and mediate subsequent cell signalling events. In this study, neural stem cells were transplanted into the traumatically injured mouse brain within a tissue-engineered construct containing either a laminin- or fibronectin-based scaffold. Cells delivered within the scaffolds were more widely distributed in the injured brain compared to cells delivered in media alone. There were no differences in donor cell survival at 1 week post-transplant; however, by 8 weeks post-transplant, cells delivered within the scaffolds showed improved survival compared to those transplanted in media alone. Survival was more enhanced with the laminin-based scaffold compared to the fibronectin-based scaffold. Furthermore, behavioural analyses indicated that mice receiving neural stem cells within the laminin-based scaffold performed significantly better than untreated mice on a spatial learning task, supporting the notion that functional recovery correlates positively with donor cell survival. Together these results suggest that the use of appropriate extracellular matrix-based scaffolds can be exploited to improve cell transplantation therapy.

Sustained Survival and Maturation of Adult Neural Stem/Progenitor Cells after Transplantation into the Injured Brain

“…However, what is unclear is which of these environments is more conducive for cell transplant survival. Within a different post-injury environment, published studies using cell sources ranging from embryonic murine (Boockvar et al, 2005;Hoane et al, 2004;Philips et al, 2001;Riess et al, 2002;Wallenquist et al, 2009), or fetal stem cell lines (Hagan et al, 2003;Shear et al, 2004;Tate et al, 2002Tate et al, , 2009Wennersten et al, 2004), to bone marrow cells (Mahmood et al, 2001a(Mahmood et al, , 2001b(Mahmood et al, , 2003Qu et al, 2009), have reported varying degrees of cell survival after transplantation into the injured brain, both at early and later post-injury time points. Many studies have indicated that post-injury timing and location of implantation are important factors determining the fate of transplanted NS/NPCs.…”

Biomaterials for spinal cord repair

“…As a major component of basement membrane ECM, laminin has frequently been shown to influence neurite outgrowth both in vitro [42][43][44][45] and in vivo [44,[46][47][48][49] . Laminin forms a sheetlike polymer that is best known for its critical involvement in basal membrane formation.…”

The Use of a Hydrogel Matrix as a Cellular Delivery Vehicle in Future Cell-Based Therapies: Biological and Non-Biological Considerations

“…In some cases, there will be little or no space for the cells to divide into since the target tissue has no cavity (Darabi, et al, 2009;Laflamme, et al, 2007;Terrovitis, et al, 2008). It is no surprise that most transplanted cells die within 24 hours of transplantation (Bliss, et al, 2007;Guerette, et al, 1997;Snyder, et al, 2010;Suzuki, et al, 2004;Tate, et al, 2009;Terrovitis, et al, 2008;Zhong, et al, 2010 (Kaihara and Vacanti, 1999). The use of degradable polymer scaffolds is crucial since it provides an initial remodelable substrate for the cells, provides space for the cells to reorganize into more complicated tissues, and potentially can be designed to provide an initial template to guide subsequent structure formation (Kaihara and Vacanti, 1999).…”