Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique

Bakshi, Ajay; Hunter, Corey; Swanger, Sharon; Lepore, Angelo C.; Fischer, Itzhak

doi:10.3171/spi.2004.1.3.0330

Cited by 124 publications

(109 citation statements)

References 32 publications

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“…We transplanted our cells at 1-week post-compression injury, whereas the other groups used a 10 and 14 days interval after either dorsal lateral funiculotomy or contusion injury. 2,3 We suggest that extensive incision and disruption of the dura was required to make the dorsal lateral funiculus lesions 3,4 and tearing of the dura in the contusion injury 2 allowed the transplanted cells to migrate freely into the injured spinal cord parenchyma. In contrast, the clip impact-compression model, a model more relevant to human SCI, does not disrupt the dura in most animals, although it does cause a minimal meningeal inflammatory reaction in the first 2 weeks after injury that gradually diminishes over time.…”

Section: Resultsmentioning

confidence: 99%

“…A small longitudinal incision was made over the L3-5 spinous processes and the skin was retracted, as described previously. 3,19 A neonatal 25-gauge LP needle was advanced into the spinal canal at L3-4 or L4-5. Proper placement of the needle was determined by the presence of cerebrospinal fluid (CSF) in the hub of the needle.…”

Section: Compression Sci and Lp Transplantationmentioning

confidence: 99%

“…A potential alternative is intrathecal transplantation via lumbar puncture (LP), a method that is frequently used in humans 1 but it has received minimal experimental investigation. [2][3][4] The intrathecal technique of cell injection has also been used in other animal models. [5][6][7] However, the phenotype of LP transplanted neural stem/progenitor cells (NSPCs) and bone marrow-derived mesenchymal stromal cells (BMSCs) and their spatial distribution along the intact and injured spinal cord has not been reported or quantitated.…”

Section: Introductionmentioning

confidence: 99%

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Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

et al. 2011

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Study design: Experimental investigation of intrathecal transplantation of stem cells by lumbar puncture (LP) in a rat model that simulates human thoracic spinal cord injury (SCI). Objectives: To examine the distribution and phenotype of spinal cord-derived neural stem/progenitor cells (NSPCs) and bone marrow-derived mesenchymal stromal cells (BMSCs) following LP transplantation in SCI rats. Setting: Toronto Western Research Institute, Toronto, Ontario, Canada. Methods: NSPCs or BMSCs were transplanted via LP at level L3-5 1 week after compression SCI at T8. Rats were killed at 3, 17 and 27 days after LP transplantation and the relative distribution of cells at C4, T8 and L3-5 was quantitated. The phenotype of the NSPC and BMSC was assessed with immunocytochemistry in vitro and following LP transplantation. Results: By 4 weeks, more NSPC migrated to the lesion site relative to BMSC and uninjured animals. However, there was no preferential homing of either of these types of cells into the parenchyma of the injury site, and most of the transplanted cells remained in the intrathecal space. In vitro, spinal cord-derived NSPC proliferated and expressed nestin, but after LP transplantation, NSPC became post-mitotic and primarily expressed oligodendrocyte markers. In contrast, BMSC did not express any neural antigens in vivo. Conclusion: LP is a minimally invasive method of cell transplantation that produces wide dissemination of cells in the subarachnoid space of the spinal cord. This is the first study to report and quantify the phenotype and spatial distribution of LP transplanted NSPC and BMSC in the intact and injured spinal cord.

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Section: Resultsmentioning

confidence: 99%

Section: Compression Sci and Lp Transplantationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

et al. 2011

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“…MSC are attractive candidates for transplantation therapies because they can be easily harvested and expanded, they have the potential for autologous transplantation, they appear to "home" to the site of injury (26,27) and they do not carry the ethical burden of embryonic stem cells. To date, studies using MSC in different disease/injury models have yielded varying results.…”

Section: Discussionmentioning

confidence: 99%

Effects of plating density and culture time on bone marrow stromal cell characteristics

Neuhuber

Swanger

Howard

et al. 2008

Experimental Hematology

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Objective-Bone marrow stromal cells (MSC) are multipotent adult stem cells that have emerged as promising candidates for cell therapy in disorders including cardiac infarction, stroke and spinal cord injury. While harvesting methods used by different laboratories are relatively standard, MSC culturing protocols vary widely. This study is aimed at evaluating the effects of initial plating density and total time in culture on proliferation, cell morphology, and differentiation potential of heterogeneous MSC cultures and more homogeneous cloned subpopulations.Methods-Rat MSC were plated at 20, 200 and 2000 cells/cm 2 and grown to 50% confluency. The numbers of population doublings and doubling times were determined within and across multiple passages. Changes in cell morphology and differentiation potential to adipogenic, chondrogenic, and osteogenic lineages were evaluated and compared among early, intermediate and late passages, as well as between heterogeneous and cloned MSC populations.Results-We found optimal cell growth at a plating density of 200 cells/cm 2 . Cultures derived from all plating densities developed increased proportions of flat cells over time. Assays for chondrogenesis, osteogenesis and adipogenesis showed that heterogeneous MSC plated at all densities sustained the potential for all three mesenchymal phenotypes through at least passage 5; the flat subpopulation lost adipogenic and chondrogenic potential.Conclusion-Our findings suggest that the initial plating density is not critical for maintaining a well-defined, multipotent MSC population. Time in culture, however, affects cell characteristics, suggesting that cell expansion should be limited, especially until the specific characteristics of different MSC subpopulations are better understood. Keywordsadult stem cells; heterogeneity; variability; differentiation potential; expansion Bone marrow stromal cells (MSC) represent a heterogeneous population derived from the nonblood forming fraction of bone marrow that regulates hematopoietic cell development. In vitro, adult mesenchymal stem cells resident in this bone marrow fraction differentiate into bone, cartilage and fat (1). Cultured MSC have also been shown to regenerate cardiac (2) and Correspondence: Birgit Neuhuber, Ph.D, Department of Neurobiology and Anatomy, Drexel University College of Medicine, 2900 Queen Lane, Philadelphia, PA 19129, Phone: (215) Fax: (215) 843-9803, E-mail: bneuhuber@drexelmed.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In this study, we cultured rat MSC for which no effort was made to limit heterogene...

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“…LP was originally well known to extract the cerebrospinal fluid or applying drugs locally to the spinal cord [36]. Recently, LP was also reported as a less invasive method for cell transplantation into the spinal cord [37][38][39].…”

Section: Discussionmentioning

confidence: 99%

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

et al. 2010

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We investigated the therapeutic potential of mouse ESCderived gamma-amino butyric acid (GABA)ergic neurons ($74% of total neurons in vitro) to reduce neuropathic pain following spinal cord injury (SCI) in rats. Spinal cord hemisection at the T13 segment, which is used as a rat SCI pain model, induced tactile hypersensitivity of the hind paw, as evidenced by decreased paw withdrawal thresholds in response to von Frey filaments, and also induced hyperexcitability of wide dynamic range neurons in the lumbar spinal cord in response to natural cutaneous stimuli. At 2 weeks posthemisection, GABAergic neurons (500,000 cells) were transplanted into the subarachnoid space of the spinal lumbar enlargement via a modified lumbar puncture technique. The transplantation of GABAergic neurons led to long-term attenuation of hemisection-induced tactile hypersensitivity and neuronal hyperexcitability as compared with vehicle-treated controls. These attenuations were reversed by the application of bicuculline and CGP52432, GABA-A and GABA-B receptor antagonists, respectively, but not by application of the serotonergic receptor antagonist methylsergide, indicating a specific restoration of spinal GABAergic inhibition. Histological data from sections of the lumbar cord in grafts demonstrated that 43.5% of surviving engrafted cells were neurons and located densely in the lower-medial portion of the dorsal funiculi in the spinal white matter. Among the observed neurons, 26.2% were GABAergic. The results suggest that subarachnoid transplantation of ESC-derived GABAergic neurons appear to restore spinal GABAergic inhibitory tone and can be a promising strategy to treat SCI-induced pain.

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Minimally invasive delivery of stem cells for spinal cord injury: advantages of the lumbar puncture technique

Cited by 124 publications

References 32 publications

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

Intrathecal transplantation of stem cells by lumbar puncture for thoracic spinal cord injury in the rat

Effects of plating density and culture time on bone marrow stromal cell characteristics

Transplantation of GABAergic Neurons from ESCs Attenuates Tactile Hypersensitivity Following Spinal Cord Injury

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