Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats

Abstract

Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult ratsAims: Previous studies on the therapeutic time window for intravascular administration of bone marrow stem cells (BMSCs) after stroke have shown that early intervention (from 3 h after onset) in the middle cerebral artery occlusion (MCAO) rat model is the most effective approach to reduce ischaemic lesion size. We have confirmed these observations but noticed that 2 weeks after transplantation, almost none of the grafted BMSCs could be detected in or around the lesion. The present experiments aimed to assess the fate and kinetics of intravascularly injected BMSCs shortly after administration in correlation to the development of the ischaemic lesion after MCAO. Methods: We administered a syngeneic suspension of complete (haematopoietic and mesenchymal) BMSCs via the carotid artery to rats at 2 h after MCAO onset. We examined the distribution and tissue location of BMSCs within the first 24 h after arterial administration by perfusion-fixating rats and performing immunohistochemical analysis at different time points. Results: The vast majority (>95%) of BMSCs appeared to become trapped in the spleen shortly after injection. Six hours after implantation, together with the appearance of activated microglia, the first BMSCs could be detected in and around the lesion; their number gradually increased during the first 12 h after implantation but started to decrease at 24 h. The implanted BMSCs were surrounded by activated and phagocytotic microglia. Conclusion: Our results show that ischaemic lesion size reduction can already be achieved by the early transient presence at the lesion site of intravascularly implanted BMSCs, possibly mediated via activated microglia.

Autologous Bone Marrow Mesenchymal Stem Cell Therapy in the Subacute Stage of Traumatic Brain Injury by Lumbar Puncture

“…8,9 Furthermore, several studies have reported that transplanted BMSCs accelerate neuroplasticity and facilitate neuronal regeneration, as well as functional recovery. [10][11][12][13][14] Therefore, BMSC therapy may be a novel method to repair brain lesions and promote patients with functional disorders after severe TBI. Here, we report our experiences with autologous BMSC transplant that we have used in a clinical trial for patients with TBI complications.…”

The isolation and cultivation of bone marrow stem cells and evaluation of differences for neural-like cells differentiation under the induction with neurotrophic factors

“…Recently, there has been increasing interest in the study in which injured neural components were replaced by BMSCs that can be easily isolated from small aspirates of bone marrow and expanded in culture (Hofstetter et al 2002;Shimizu et al 2007;Keimpema et al 2009). …”

“…Currently, there are several methods for the induction of differentiation of MSCs into neural cells: (1) exposure to inducing cytokine and neurotrophic factors, such as NGF, GDNF, and EGF (Low et al 2008;Cohen et al 2011;Keimpema et al 2009 exposure to chemical inducers such as b-mercaptoethanol, DMSO, and glutathione (Woodbury et al 2000;Kang et al 2006;Sagara and Makino 2008); (3) a combination of cytokines and chemical inducers; (4) other methods including exposure to traumatic brain homogenate, co-culture in or exposure to culture medium/Chinese medicines (Yong et al 2008;Wang et al 2009). Differentiation of MSC to neuron-like cells was firstly reported by Woodbury et al (2000), but increasing researches found that chemical inducers had negative effects on viability of MSC during induction in vitro.…”

Immunopathogenetic Aspects of Ischemic Stroke

“…Удаление селезенки или ее облучение перед или сразу после окклю-зии мозговой артерии уменьшает размеры ише-мического инфаркта и улучшает восстановление [90,137]. В этом аспекте терапевтический потен-циал стволовых клеток в моделях ишемического поражения головного мозга может быть в значи-тельной мере опосредован их способностью по-давлять провоспалительный ответ со стороны се-лезенки [56,108,142].…”