Histological and functional outcomes in a rat model of hemisected spinal cord with sustained VEGF/NT-3 release from tissue-engineered grafts

Abstract

Microvascular disturbance, excessive inflammation and gliosis are key pathophysiologic changes in relation to functional status following the traumatic spinal cord injury (SCI). Continuous release of vascular endothelial growth factor (VEGF) to the lesion site was proved be able to promote the vascular remodelling, whereas the effects on reduction of inflammation and gliosis remain unclear. Currently, aiming at exploring the synergistic roles of VEGF and neurotrophin-3 (NT-3) on angiogenesis, anti-inflammation and neural repair, we developed a technique to co-deliver VEGF 165 and NT-3 locally with a homotopic graft of tissue-engineered acellular spinal cord scaffold (ASCS) in a hemisected (3 mm in length) SCI model. As the potential in secretion of growth factors (GFs), bone mesenchymal stem cells (BMSCs) were introduced with the aim to enhance the VEGF/NT-3 release. Our data demonstrate that sustained VEGF/NT-3 release from ASCS significantly increases the local levels of VEGF/NT-3 and angiogenesis, regardless of whether it is in combination with BMSCs transplantation that exhibits positive effects on anti-inflammation, axonal outgrowth and locomotor recovery. This study verifies that co-delivery of VEGF/NT-3 reduces inflammation and gliosis in the hemisected spinal cord, promotes axonal outgrowth and results in better locomotor recovery, while the BMSCs transplantation facilitates these functions limitedly.

Biomaterials in Neurodegenerative Disorders: A Promising Therapeutic Approach

“…More recently, it was shown that the use of iron oxide nanoparticles along with electromagnetic fields induced sprouting from mature neurons and axons, significantly less demyelination and more myelinated fibers in injured rats [101]. Other factors such as neurotrophins [102,103] and the enzyme chABC [104], which has already been seen as a promising treatment for SCI, have been loaded in NPs, showing that they can induce axon regrowth with a controlled and sustained release at the site of the lesion.…”

Select neurotrophins promote oligodendrocyte progenitor cell process outgrowth in the presence of chondroitin sulfate proteoglycans

“…NT‐3 has also been shown to enhance neuronal survival and stimulate regenerative sprouting following SCI (Han et al., 2019; Li et al., 2016; Tobias et al., 2003; Xu et al., 2020). Moreover, it can enhance the survival of OPCs, both in vitro and in vivo (Kumar et al., 1998).…”

“…Another treatment strategy utilizes neurotrophic agents to promote neuronal survival and stimulate the regeneration of axons. Currently some of the most common neurotrophic agents utilized in spinal regeneration studies include brain‐derived neurotrophic factor (BDNF; Gransee et al., 2015; Hassannejad et al., 2019; Liu et al., 2017), glial cell line‐derived neurotrophic factor (GDNF; Chen et al., 2018; Haldeman & Manna, 2019; Tajdaran et al., 2016), and neurotrophic factor‐3 (NT‐3; Han et al., 2019; Li et al., 2016; Xu et al., 2020). In these studies, the application of neurotrophic factors can enhance neuron survival and axonal sprouting, depending on the neuronal population examined and the SCI model.…”

Biomaterial-supported MSC transplantation enhances cell–cell communication for spinal cord injury

“…MSCs can also modify the immune response after injury by elevating levels of anti-inflammatory and reducing levels of proinflammatory cytokines when transplanted 3 or 7 days after SCI. The delivery of neural progenitor cells to the site of injury triggers recovery through reducing inflammation and reactive gliosis as well as promoting angiogenesis [46] without the heightened risk of tumorigenesis. Cell therapies are commonly administered through i.v.…”