The Beneficial Potential of Genetically Modified Stem Cells in the Treatment of Stroke: a Review

Abstract

The last two decades have witnessed a surge in investigations proposing stem cells as a promising strategy to treat stroke. Since growth factor release is considered as one of the most important aspects of cell-based therapy, stem cells over-expressing growth factors are hypothesized to yield higher levels of therapeutic efficiency. In pre-clinical studies of the last 15 years that were investigating the efficiency of stem cell therapy for stroke, a variety of stem cell types were genetically modified to over-express various factors. In this review we summarize the current knowledge on the therapeutic efficiency of stem cell-derived growth factors, encompassing techniques employed and time points to evaluate. In addition, we discuss several types of stem cells, including the recently developed model of epidermal neural crest stem cells, and genetically modified stem cells over-expressing specific factors, which could elevate the restorative potential of naive stem cells. The restorative potential is based on enhanced survival/differentiation potential of transplanted cells, apoptosis inhibition, infarct volume reduction, neovascularization or functional improvement. Since the majority of studies have focused on the short-term curative effects of genetically engineered stem cells, we emphasize the need to address their long-term impact.

Therapeutic potential of hair follicle-derived stem cell intranasal transplantation in a rat model of ischemic stroke

“…Since all of these processes are essential for recovery after stroke, numerous investigations employed exogenous growth factors to treat cerebral ischemia [ 45 ]. In addition, the beneficial potential of genetically engineered stem cells over-expressing growth factors has been demonstrated in the treatment of stroke [ 46 ]. It is documented that BDNF expression increased following different types of stroke such as intracerebral hemorrhage [ 47 ] and ischemic stroke [ 48 ].…”

Genetically engineered neural stem cells (NSCs) therapy for neurological diseases; state‐of‐the‐art

“…Recent reports have indicated that overexpression of glial cell line‐derived neurotrophic factor (GDNF) regulates the expression of a diversity of genes like neuregulin1, ephrinB2‐receptor, neuritis, and focal adhesion kinase (FAK) in NSCs, thus directly influencing differentiation and developmental processes of neurons 105 . Likewise, although direct administration of brain‐derived neurotrophic factor (BDNF) provides no long‐term effects as a result of the short half‐life of BDNF, 106 its overexpression could increase the engrafted NSCs viability, neuronal fate, neurite complexity, maturation of electrical property as well as the synaptic density in vivo 107 . BDNF binds to its high‐affinity receptor tyrosine kinase B (TrkB) and subsequently induces the activation of signaling cascades, such as the Ras‐mitogen‐activated protein kinase (MAPK), the phosphatidylinositol‐3‐kinase (PI3K), and the phospholipase Cγ (PLC‐γ) signaling pathways 108,109 .…”

Treatment of ischemic stroke with modified mesenchymal stem cells

“…Although endogenous neural stem cells (NSCs) do exhibit an acute response to IS, such as increased cell proliferation and cell migration, only 10%-20% of these cells survive long-term, and only a few of these surviving cells can mature into functional cells. However, most of them develop into thorny new striatal projection neurons or calretinin-positive interneurons 84 . This hinders the differentiation of MSCs into functional nerve cells after transplantation.…”