In vivoimaging of endogenous neural stem cells in the adult brain

Abstract

The discovery of endogenous neural stem cells (eNSCs) in the adult mammalian brain with their ability to self-renew and differentiate into functional neurons, astrocytes and oligodendrocytes has raised the hope for novel therapies of neurological diseases. Experimentally, those eNSCs can be mobilized in vivo , enhancing regeneration and accelerating functional recovery after, e.g., focal cerebral ischemia, thus constituting a most promising approach in stem cell research. In order to translate those current experimental approaches into a clinical setting in the future, non-invasive imaging methods are required to monitor eNSC activation in a longitudinal and intraindividual manner. As yet, imaging protocols to assess eNSC mobilization non-invasively in the live brain remain scarce, but considerable progress has been made in this field in recent years. This review summarizes and discusses the current imaging modalities suitable to monitor eNSCs in individual experimental animals over time, including optical imaging, magnetic resonance tomography and-spectroscopy, as well as positron emission tomography (PET). Special emphasis is put on the potential of each imaging method for a possible clinical translation, and on the specificity of the signal obtained. PET-imaging with the radiotracer 3'-deoxy-3'-[18 F]fluoro-L-thymidine in particular constitutes a modality with excellent potential for clinical translation but low specificity; however, concomitant imaging of neuroinflammation is feasible and increases its specificity. The non-invasive imaging strategies presented here allow for the exploitation of novel treatment strategies based upon the regenerative potential of eNSCs, and will help to facilitate a translation into the clinical setting.

Substrate elasticity induces quiescence and promotes neurogenesis of primary neural stem cells—A biophysical in vitro model of the physiological cerebral milieu

“…Although they remain in a functional state within their specific niches throughout the lifespan of all mammals (Alvarez-Buylla & Garcia-Verdugo, 2002;Bond, Ming, & Song, 2015), the regenerative capacity of the brain is limited if substantial damage occurs (Alvarez-Buylla, Seri, & Doetsch, 2002;Sohur, Emsley, Mitchell, & Macklis, 2006). Promising research focuses on enhancing this innate regenerative capacity of the brain by explicitly targeting the endogenous NSC niche, for example, by pharmacological means (Rabenstein & Rueger, 2018;Rueger & Schroeter, 2015;Vay et al, 2016). However, research on NSC grown in cell culture always faces the problem of artificiality when compared with the in vivo situation because NSC functions crucially depend on the microenvironment in the stem cell niche (Doetsch, 2003;Regalado-Santiago, Juarez-Aguilar, Olivares-Hernandez, & Tamariz, 2016).…”

Fifty years of brain imaging in neonatal encephalopathy following perinatal asphyxia

“…Recent studies have demonstrated that several PET techniques may be able to identify human stem cells in stroke patients (55), and discriminate between nonviable and viable (penumbra) tissue, which may be relevant for future trials studying neuroprotective strategies (56).…”

Neural stem cell niches in the adult mammalian brain

“…The presence of neural genesis in the brain of adults was confirmed in 1998, when Fred Gage and Swedish neurobiologist Peter Eriksson first demonstrated the formation of new neurons in the human hippocampus [14]. Today there is no doubt about the existence of permanent neurogenesis in some areas of the brain of adult mammals, which is provided by a pool of neural stem cells (NSCs) [7,8,32,38,49].…”