Article

Regeneration of the ischemic brain by engineered stem cells: fuelling endogenous repair processes.

Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Brain Research Reviews (Impact Factor: 5.93). 05/2009; 61(1):1-13. DOI: 10.1016/j.brainresrev.2009.03.003
Source: PubMed

ABSTRACT After ischemic brain injury various cell types including neurons, glia and endothelial cells are damaged and lose their function. Effective regeneration of brain tissue requires that all these cell types have to be replenished and combined to form a new functional network. Recent advances in regenerative medicine show the ability of stem cells to differentiate into various cell lineages. Several types of stem cells have been used to treat ischemic brain injury in rodent models including neuronal stem cells, mesenchymal stem cells and hematopoietic stem cells. Although these studies show promising results, it remains to be determined whether the beneficial effect of cell-based therapies in ischemic brain injury results from direct replacement of damaged cells by the transplanted cells. On the basis of the current literature we propose that neuroprotection by activation of anti-apoptotic mechanisms as well as improvement of the trophic milieu necessary for endogenous repair processes may be more important mechanisms underlying the improved functional outcome after stem cell treatment. Transplantation of native unmodified stem cells as such may not be sufficient to boost repair mechanisms provided by the endogenous stem cell population. An important aim of this review is to discuss the literature on the possible enhancement of regenerative function by combining stem cell transplantation with gene transduction into stem cells to enhance their regenerative and neuroprotective therapeutic potential. Finally, we briefly discuss the possibility of translation of this therapy to the clinic.

0 Bookmarks
 · 
126 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxic-ischemic (HI) brain injury is one of the main causes of disabilities in term-born infants. It is the result of a deprivation of oxygen and glucose in the neural tissue. As one of the most important causes of brain damage in the newborn period, the neonatal HI event is a devastating condition that can lead to long-term neurological deficits or even death. The pattern of this injury occurs in two phases, the first one is a primary energy failure related to the HI event and the second phase is an energy failure that takes place some hours later. Injuries that occur in response to these events are often manifested as severe cognitive and motor disturbances over time. Due to difficulties regarding the early diagnosis and treatment of HI injury, there is an increasing need to find effective therapies as new opportunities for the reduction of brain damage and its long term effects. Some of these therapies are focused on prevention of the production of reactive oxygen species, anti-inflammatory effects, anti-apoptotic interventions and in a later stage, the stimulation of neurotrophic properties in the neonatal brain which could be targeted to promote neuronal and oligodendrocyte regeneration.
    Brain sciences. 03/2013; 3(1):191-214.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effective treatment for cerebral ischemia has not yet been established. Hepatocyte growth factor (HGF) is a potent pleiotropic cytokine that is involved in cell and tissue regeneration, including in the central nervous system. Studies have demonstrated that an exogenous administration of HGF protects brain tissue from ischemic damage. In response to binding to the receptor c-Met, HGF activates the downstream signaling pathways (including the phosphatidylinositol 3-kinase/Akt, Ras/MAPK and signal transducer and activator of transcription pathways) which leads to various cellular responses involved in angiogenesis, glial scar formation, anti-apoptosis and neurogenesis. The purpose of this review is to summarize the present understanding of the therapeutic potential of HGF in cerebral ischemia.
    Experimental and therapeutic medicine 02/2015; 9(2):283-288. · 0.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: According to the traditional understanding of cerebrospinal fluid (CSF) physiology, the majority of CSF is produced by the choroid plexus, circulates through the ventricles, the cisterns, and the subarachnoid space to be absorbed into the blood by the arachnoid villi. This review surveys key developments leading to the traditional concept. Challenging this concept are novel insights utilizing molecular and cellular biology as well as neuroimaging, which indicate that CSF physiology may be much more complex than previously believed. The CSF circulation comprises not only a directed flow of CSF, but in addition a pulsatile to and fro movement throughout the entire brain with local fluid exchange between blood, interstitial fluid, and CSF. Astrocytes, aquaporins, and other membrane transporters are key elements in brain water and CSF homeostasis. A continuous bidirectional fluid exchange at the blood brain barrier produces flow rates, which exceed the choroidal CSF production rate by far. The CSF circulation around blood vessels penetrating from the subarachnoid space into the Virchow Robin spaces provides both a drainage pathway for the clearance of waste molecules from the brain and a site for the interaction of the systemic immune system with that of the brain. Important physiological functions, for example the regeneration of the brain during sleep, may depend on CSF circulation.
    Fluids and barriers of the CNS. 01/2014; 11:10.

Full-text

Download
11 Downloads
Available from
Aug 19, 2014