The Endogenous Regenerative Capacity of the Damaged Newborn Brain: Boosting Neurogenesis with Mesenchymal Stem Cell Treatment

Abstract

Neurogenesis continues throughout adulthood. The neurogenic capacity of the brain increases after injury by, e.g., hypoxiaischemia. However, it is well known that in many cases brain damage does not resolve spontaneously, indicating that the endogenous regenerative capacity of the brain is insufficient. Neonatal encephalopathy leads to high mortality rates and long-term neurologic deficits in babies worldwide. Therefore, there is an urgent need to develop more efficient therapeutic strategies. The latest findings indicate that stem cells represent a novel therapeutic possibility to improve outcome in models of neonatal encephalopathy. Transplanted stem cells secrete factors that stimulate and maintain neurogenesis, thereby increasing cell proliferation, neuronal differentiation, and functional integration. Understanding the molecular and cellular mechanisms underlying neurogenesis after an insult is crucial for developing tools to enhance the neurogenic capacity of the brain. The aim of this review is to discuss the endogenous capacity of the neonatal brain to regenerate after a cerebral ischemic insult. We present an overview of the molecular and cellular mechanisms underlying endogenous regenerative processes during development as well as after a cerebral ischemic insult. Furthermore, we will consider the potential to use stem cell transplantation as a means to boost endogenous neurogenesis and restore brain function.

Preconditioning with VEGF Enhances Angiogenic and Neuroprotective Effects of Bone Marrow Mononuclear Cell Transplantation in a Rat Model of Chronic Cerebral Hypoperfusion

“…However, the underlying mechanism of action for intravenous transplantation of BMMNCs in ischemic diseases is unclear. Some investigators have shown that transplanted cells, such as MSCs [39], neural stem cells [40], endothelial progenitor cells [41], and BMMNCs [7, 19, 28], are able to migrate to the ischemic lesion, remain viable, and function effectively via paracrine effects or cell differentiation. However, others have reported that, after intravenous delivery, most BMMNCs are initially trapped in the lungs or liver [14, 42].…”

GDF-15 Secreted from Human Umbilical Cord Blood Mesenchymal Stem Cells Delivered Through the Cerebrospinal Fluid Promotes Hippocampal Neurogenesis and Synaptic Activity in an Alzheimer's Disease Model

“…Our study demonstrated that endogenous adult hippocampal neurogenesis was promoted through an hUCB-MSC paracrine mechanism, which is the basis for the effects of hUCB-MSCs in AD. Unlike previous studies that demonstrated that MSCs promote neurogenesis [30,43,44], we utilized the Transwell coculture system to identify increased levels of GDF-15 secreted from hUCB-MSCs by analyzing cytokine antibody arrays. GDF-15, which is a member of the transforming growth factor superfamily [45,46], is a neurotrophic factor that affects adult motor and dorsal root ganglion sensory neurons [33,34].…”

Therapeutic potential to reduce brain injury in growth restricted newborns

“…without treatment) after injury (Donega et al . ). Postnatal treatments have been shown to induce neuronal regeneration in neonatal HI models (reviewed in Donega et al .…”

“…Postnatal treatments have been shown to induce neuronal regeneration in neonatal HI models (reviewed in Donega et al . ); therefore it is important to detect growth restriction early to maximise the chance an intervention will have to prevent long‐term adverse neurological outcomes.…”