Mesenchymal stem cell‐based treatments for stroke, neural trauma, and heat stroke

Abstract

BackgroundMesenchymal stem cell (MSC) transplantation has been reported to improve neurological function following neural injury. Many physiological and molecular mechanisms involving MSC therapy‐related neuroprotection have been identified.MethodsA review is presented of articles that pertain to MSC therapy and diverse brain injuries including stroke, neural trauma, and heat stroke, which were identified using an electronic search (e.g., PubMed), emphasize mechanisms of MSC therapy‐related neuroprotection. We aim to discuss neuroprotective mechanisms that underlie the beneficial effects of MSCs in treating stroke, neural trauma, and heatstroke.Results MSC therapy is promising as a means of augmenting brain repair. Cell incorporation into the injured tissue is not a prerequisite for the beneficial effects exerted by MSCs. Paracrine signaling is believed to be the most important mediator of MSC therapy in brain injury. The multiple mechanisms of action of MSCs include enhanced angiogenesis and neurogenesis, immunomodulation, and anti‐inflammatory effects. Microglia are the first source of the inflammatory cascade during brain injury. Cytokines, including tumor necrosis factor‐α, interleukin‐1β, and interleukin‐6, are significantly produced by microglia in the brain after experimental brain injury. The proinflammatory M1 phenotype of microglia is associated with tissue destruction, whereas the anti‐inflammatory M2 phenotype of microglia facilitates repair and regeneration. MSC therapy may improve outcomes of ischemic stroke, neural trauma, and heatstroke by inhibiting the activity of M1 phenotype of microglia but augmenting the activity of M2 phenotype of microglia.ConclusionThis review offers a testable platform for targeting microglial‐mediated cytokines in clinical trials based upon the rational design of MSC therapy in the future. MSCs that are derived from the placenta provide a great choice for stem cell therapy. Although targeting the microglial activation is an important approach to reduce the burden of the injury, it is not the only one. This review focuses on this specific aspect.

The Role of Astrocytes in Neuroprotection after Brain Stroke: Potential in Cell Therapy

“…Transplantation models have been reported in cerebral ischemia mainly using mesenchymal stem cells (MSC; Hsuan et al, 2016; Lee et al, 2016), induced pluripotent stem cells (iPSCs; Mohamad et al, 2013), and NSCs (Huang et al, 2014; Gervois et al, 2016), showing that there is stimulus of endogenous activity of cells in the injured tissue, generating increased angiogenesis/neovascularization and release of trophic factors, which is chiefly secreted by these cells, allowing the migration to the lesion zone. Likewise, there is axonal recovery, dendritic branching, and synaptogenesis, which are reported mainly surrounding the injury site (Horie et al, 2015).…”

Mesenchymal Stem Cells Improve Healing of Diabetic Foot Ulcer

“…Nowadays, a growing number of diseases can be improved via wide applications of stem cell transplantation, such as congenital cataract [12], diabetic retinopathy and keratopathy [13], myocardial infarction [14], ocular surface burns [15, 16], serious skin burns [17, 18], Parkinson's disease [19], Huntington's disease [20], and especially DFU [21]. Accumulating evidence has pointed out that mesenchymal stem cells (MSCs) may enhance wound healing [22–24] and be served as a cell source for many tissue engineering applications including bone regeneration [25], cartilage regeneration [26–28], myocardial regeneration [29], neurogenesis [30, 31], inflammatory bowel diseases [32], and DFU [33, 34]. MSCs exist in many tissues, for example, bone marrow [35, 36], umbilical cord [37, 38], placenta [39, 40], adipose tissue [36, 41–43], gingiva [44, 45], oral mucosa [46], amniotic fluid [47], and brain [48].…”

Therapeutic potential of mesenchymal stem cells for diabetes

“…Preclinical studies in cardiac and brain ischemia support the concept that MSCs improve structural and functional outcomes by repairing and stimulating the growth of blood vessels (Acosta et al 2013; Hsuan et al 2016). The angiogenic properties of MSCs is mediated through the release of hypoxia inducible factor, vascular endothelial growth factor, angiopoietin, and erythropoietin.…”