Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits

Liu, Wenpeng; Jiang, Xiao-dan; Fu, Xiafei; Cui, Shaojie; Du, Ming; Cai, Yuchen; Xu, Ran

doi:10.1016/j.neulet.2007.12.067

Cited by 17 publications

(7 citation statements)

References 23 publications

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“…However, we found abundant Ad-MSC in the subarachnoid space in the diencephalon, midbrain, medulla oblongata, and spinal cord. This finding is not consistent with previous studies that intrathecally transplanted various stem cells migrated into the parenchyma in some CNS disease models, such as animal models of amyotrophic lateral sclerosis, traumatic brain, and ischemic spinal cord injury (Lepore et al 2005;Habisch et al 2007;Liu et al 2008;Kim et al 2010). The difference in the distribution and migration of the transplanted stem cells may be associated with conditions of the brain, e.g., intact or damaged brain because the migration of transplanted stem cells is influenced by various factors, such as cell death and inflammatory cytokines under a disease condition (Sugaya 2003;Nervi et al 2006;Newby 2006).…”

Section: Discussioncontrasting

confidence: 92%

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

et al. 2011

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Mesenchymal stem cells (MSC) have emerged as a new therapeutic tool for a number of clinical applications, because they have multipotency and paracrine effects via various factors. In the present study, we investigated the effects of adipose-derived MSC (Ad-MSC) transplantation via intrathecal injection through the cisterna magna on cell proliferation and differentiation of endogenous stem cells in the hippocampal dentate gyrus (DG) using Ki-67 (a marker for proliferating cells), and doublecortin (DCX, a marker for neuroblasts). The transplanted Ad-MSC were detected in the meninges, not in the hippocampal parenchyma. However, the number of Ki-67-immunoreactive cells was significantly increased by 83% in the DG 2 days after single Ad-MSC injection, and by 67% at 23 days after repeated Ad-MSC treatment compared with that in the vehicle-treated group after Ad-MSC transplantation. On the other hand, the number of DCX-immunoreactive cells in the DG was not changed at 2 days after single Ad-MSC injection; however, it was significantly increased by 62% 9 days after single Ad-MSC injection. At 23 days after repeated Ad-MSC application, the number of DCX-immunoreactive cells was much more increased (223% of the vehicle-treated group). At this time point, DCX protein levels were also significantly increased compared with those in the vehicle-treated group. These results suggest that the intrathecal injection of Ad-MSC could enhance endogenous cell proliferation, and the repeated Ad-MSC injection could be more efficient for an enhancement of endogenous cell proliferation and differentiation in the brain.

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Section: Discussioncontrasting

confidence: 92%

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

et al. 2011

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“…Direct intracerebral26,29), intravascular13,15,18,55,59), intrathecal41), and intraventricular32) delivery of cells for transplantation have been tested. Intravascular delivery presents such advantages as safety and wide distribution of stem cells within the ischemic penumbra as compared to other method.…”

Section: Introductionmentioning

confidence: 99%

Engraftment of Human Mesenchymal Stem Cells in a Rat Photothrombotic Cerebral Infarction Model : Comparison of Intra-Arterial and Intravenous Infusion Using MRI and Histological Analysis

Byun

Kwak

Kim

et al. 2013

J Korean Neurosurg Soc

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ObjectiveThis study aimed to evaluate the hypotheses that administration routes [intra-arterial (IA) vs. intravenous (IV)] affect the early stage migration of transplanted human bone marrow-derived mesenchymal stem cells (hBM-MSCs) in acute brain infarction.MethodsMale Sprague-Dawley rats (n=40) were subjected to photothrombotic infarction. Three days after photothrombotic infarction, rats were randomly allocated to one of four experimental groups [IA group : n=12, IV group : n=12, superparamagnetic iron oxide (SPIO) group : n=8, control group : n=8]. All groups were subdivided into 1, 6, 24, and 48 hours groups according to time point of sacrifice. Magnetic resonance imaging (MRI) consisting of T2 weighted image (T2WI), T2* weighted image (T2*WI), susceptibility weighted image (SWI), and diffusion weighted image of rat brain were obtained prior to and at 1, 6, 24, and 48 hours post-implantation. After final MRI, rats were sacrificed and grafted cells were analyzed in brain and lung specimen using Prussian blue and immunohistochemical staining.ResultsGrafted cells appeared as dark signal intensity regions at the peri-lesional zone. In IA group, dark signals in peri-lesional zone were more prominent compared with IV group. SWI showed largest dark signal followed by T2*WI and T2WI in both IA and IV groups. On Prussian blue staining, IA administration showed substantially increased migration and a large number of transplanted hBM-MSCs in the target brain than IV administration. The Prussian blue-positive cells were not detected in SPIO and control groups.ConclusionIn a rat photothrombotic model of ischemic stroke, selective IA administration of human mesenchymal stem cells is more effective than IV administration. MRI and histological analyses revealed the time course of cell migration, and the numbers and distribution of hBM-MSCs delivered into the brain.

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“…Intrathecal infusion of NSCs after hemisection of the cervical spinal cord has shown migration to the site of injury with cellular engraftment at up to 5 weeks later [31]. In a rabbit TBI model, intrathecal infusion of MSCs showed increased cellular engraftment with improved motor functioning [32]. While intrathecal delivery offers easy access and allows for the delivery of a large number of cells to an area near the injury, the safety of this approach, along with the ultimate effectiveness of delivery to the optimal location, remain unknown.…”

Section: Current Stem Cell Delivery Methodsmentioning

confidence: 99%

Advances in Progenitor Cell Therapy Using Scaffolding Constructs for Central Nervous System Injury

Walker¹,

Aroom²,

Jiménez³

et al. 2009

Stem Cell Rev and Rep

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Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and intra arterial infusion have shown low engraftment rates and risk of distal emboli. Novel delivery methods such as nanofiber scaffold implantation could provide the structural and nutritive support Correspondence to: Charles S. Cox, Jr, charles.s.cox@uth.tmc.edu. NIH Public AccessAuthor Manuscript Stem Cell Rev. Author manuscript; available in PMC 2010 May 24. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript required for progenitor cell proliferation, engraftment, and differentiation. The focus of this review is to explore the current state of the art as it relates to current and novel progenitor cell delivery methods.

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Bone marrow stromal cells can be delivered to the site of traumatic brain injury via intrathecal transplantation in rabbits

Cited by 17 publications

References 23 publications

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

Cell Proliferation and Neuroblast Differentiation in the Rat Dentate Gyrus After Intrathecal Treatment with Adipose-Derived Mesenchymal Stem Cells

Engraftment of Human Mesenchymal Stem Cells in a Rat Photothrombotic Cerebral Infarction Model : Comparison of Intra-Arterial and Intravenous Infusion Using MRI and Histological Analysis

Advances in Progenitor Cell Therapy Using Scaffolding Constructs for Central Nervous System Injury

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