Stem cell therapy in intracerebral hemorrhage rat model

Abstract

Intracerebral hemorrhage (ICH) is a very complex pathology, with many different not fully elucidated etiologies and prognostics. It is the most severe subtype of stroke, with high mortality and morbidity rates. Unfortunately, despite the numerous promising preclinical assays including neuroprotective, anti-hypertensive, and anti-inflammatory drugs, to this moment only symptomatic treatments are available, motivating the search for new alternatives. In this context, stem cell therapy emerged as a promising tool. However, more than a decade has passed, and there is still much to be learned not only about stem cells, but also about ICH itself, and how these two pieces come together. To date, rats have been the most widely used animal model in this research field, and there is much more to be learned from and about them. In this review, we first summarize ICH epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts. Core tip: In this review, we first summarize intracerebral hemorrhage (ICH) epidemiology, risk factors, and pathophysiology. We then present different methods utilized to induce ICH in rats, and examine how accurately they represent the human disease. Next, we discuss the different types of stem cells used in previous ICH studies, also taking into account the tested transplantation sites. Finally, we summarize what has been achieved in assays with stem cells in rat models of ICH, and point out some relevant issues where attention must be given in future efforts.Cordeiro MF, Horn AP. Stem cell therapy in intracerebral hemorrhage rat model. World J Stem Cells 2015; 7(3): 618-629

After Intracerebral Hemorrhage, Oligodendrocyte Precursors Proliferate and Differentiate Inside White-Matter Tracts in the Rat Striatum

“…Strategies to treat white-matter injury focus on reducing oligodendrocyte loss, adding growth factors to promote their proliferation, maturation, and re-myelination, or supplementing with exogenous stem cells [ 99 , 100 ]. Although stem cell replacement is used in experimental studies of ischemic stroke, and injected mesenchymal stem cells can differentiate into oligodendrocytes (as well as neurons and astrocytes [ 101 ]), there is surprisingly little evidence supporting any of these approaches after ICH.…”

Human Placenta-Derived Mesenchymal Stem Cells Reduce Mortality and Hematoma Size in a Rat Intracerebral Hemorrhage Model in an Acute Phase

“…Stem cell therapy is currently regarded as one of the most promising strategies for the treatment of many incurable diseases and has shown neuroprotective effects on various neuronal injury and degenerative disease models. Various preclinical studies have also shown the beneficial neuroprotective effects of stem cell therapy for ICH via secretion of neurotrophic factors [ 8 , 9 ].…”

“…Recently, recombinant coagulation factor VII administration, an approach to improve the prognosis of acute ICH by limiting early hematoma growth via the factor's acute hemostatic effect, showed potential benefits in an early-phase clinical trial but failed to show a significant effect in a phase III clinical trial [ 15 , 16 ]. Most studies of stem cell therapy for ICH have focused on neuronal death, functional outcome, and hematoma size in subacute-to-chronic stages of the disease but not on the prognosis of the acute-stage or early hematoma expansion [ 8 , 9 ]. Results of recent studies showing that the administration of mesenchymal stem cells (MSCs) prevents blood-brain barrier (BBB) disruption and endothelial damage suggest that MSCs may improve the prognosis of ICH through the prevention of ongoing bleeding in the acute stage by intensification of the cerebral vasculature [ 17 , 18 ].…”

Review of Preclinical and Clinical Studies of Bone Marrow‐Derived Cell Therapies for Intracerebral Hemorrhage

“…In this scenario, cell-based therapies represent a promising approach for the treatment of hemorrhagic stroke. Accumulating evidence suggests that different types of stem cells have the potential to induce or accelerate functional recovery in animal models of ICH and subarachnoid hemorrhage (SAH) [ 12 – 14 ]. As described by Hu et al [ 12 ], mesenchymal stem cells (MSC) and neural stem cells were the most frequent cell types investigated in these studies.…”