Technical aspects of spinal cord injections for cell transplantation. Clinical and translational considerations

Guest, James D.; Benavides, Francisco; Padgett, Kyle R.; Méndez, Eric Ramos; Tovar, Diego

doi:10.1016/j.brainresbull.2010.11.007

Cited by 53 publications

(58 citation statements)

References 83 publications

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“…It is important to recognize that injections of these same substances, using identical methods, did not cause detectable neuronal loss in rodents. Although injections of small volumes of drugs and solutes can be made into the central nervous system without obvious tissue damage, therapeutic spinal cord injections may carry additional challenges [53][54][55]. Often there is pre-existing tissue damage, delivery volumes may be large, and cell or solute concentrations are high.…”

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

“…Injection injury likely occurs through mechanisms similar to traumatic injury, such as compression, laceration, excitotoxicity, apoptosis, and ischemia. Also, pressure-based injections of larger volumes may lead to damage through elevated intraparenchymal pressures that consequently result in hydrodynamic tissue dissection and possible ischemia [53]. The finding that injections into the primate spinal cord cause cell loss that is not observed in rodent models highlights the need for preclinical testing of therapies in primates [53,55].…”

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

“…Also, pressure-based injections of larger volumes may lead to damage through elevated intraparenchymal pressures that consequently result in hydrodynamic tissue dissection and possible ischemia [53]. The finding that injections into the primate spinal cord cause cell loss that is not observed in rodent models highlights the need for preclinical testing of therapies in primates [53,55]. It is better to discover negative side effects from therapies or techniques in an animal model rather than having human clinical trials fail for unknown reasons.…”

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

“…Further research is required in the field of central nervous system drug delivery methods. For example, it may be possible to prevent the "pistoning effect" (spinal cord cavity formation secondary to combined rostral-caudal and ventraldorsal motion when a needle is fixed in place) with either percutaneous endoscopy and placement of a needle into the spinal cord without it being held fixed in place [53], or with a needle that sits on the cord surface and moves with the cord [56]. Although local injection techniques have the advantage of precise delivery of injectate to the target, less invasive techniques, such as use of intrathecal injections or scaffolds, could be considered for treatment delivery.…”

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

See 3 more Smart Citations

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

et al. 2012

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Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

Section: Contributions and Implications: Methods Development For Theramentioning

confidence: 99%

See 2 more Smart Citations

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

et al. 2012

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“…Note that respiratory motions represent a common concern for many techniques for spinal cord imaging, for models of experimental SCI using an impactor, and for stereotactic intraspinal injections. 41 Solutions found in the literature are based on the use of a spinal clamp, increasing the depth of anesthesia, and on the use of respiratory machines to induce apnea. 42,43 Here, adequate stabilization of the whole spine was achieved by clamping Th13 and securing the incisor teeth to the nose cone.…”

Section: Very High Resolution Us Of Scimentioning

confidence: 99%

Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury

Soubeyrand

Badner

Vawda

et al. 2014

Journal of Neurotrauma

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Spinal cord injury (SCI) is characterized by vascular disruption with intramedullary hemorrhage, alterations in bloodspinal cord barrier integrity, and perilesional ischemia. A safe and easily applied imaging technique to quantify evolving intraspinal vascular changes after SCI is lacking. We evaluated the utility of very high resolution ultrasound (VHRUS) imaging to assess SCI-induced vascular disruption in a clinically relevant rodent model. The spinal cords of Wistar rats were lesioned at the 11th thoracic vertebra (Th11) by a 35 g 1-minute clip compression. Three-dimensional quantification of intraspinal hemorrhage using VHRUS (at an acute 90-min and subacute 24-h time point post-SCI) was compared with lesional hemoglobin and extravasated Evans blue dye measured spectrophotometrically. The anatomy of hemorrhage was comparatively assessed using VHRUS and histology. Time-lapse videos demonstrated the evolution of parenchymal hemorrhage. VHRUS accurately depicted the structural (gray and white matter) and vascular anatomy of the spinal cord (after laminectomy) and was safely repeated in the same animal. After SCI, a hyperechoic signal extended from the lesion epicenter. Significant correlations were found between VHRUS signal and hemorrhage in the acute (r = 0.88, p < 0.0001) and subacute (r = 0.85, p < 0.0001) phases and extravasated Evans blue (a measure of vascular disruption) in the subacute phase (r = 0.94, p < 0.0001). Time-lapse videos demonstrated that the expanding parenchymal hemorrhage is preceded by new perilesional hemorrhagic foci. VHRUS enables real-time quantitative live anatomical imaging of acute and subacute vascular disruption after SCI in rats. This technique has important scientific and clinical translational applications.

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Control of dissolved oxygen significantly increases the yield of skin‐derived Schwann cells during expansion in stirred suspension bioreactors

Walsh

Biernaskie

Midha

et al. 2021

Engineering Reports

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Peripheral nerve and spinal cord injuries affect millions of people worldwide often leading to lifelong disability and pain. Cell therapy using autologous Schwann cells are currently being investigated for the treatment of these injuries and are showing great potential. In particular, skin-derived Schwann cells offer a non-invasive option for highly therapeutic cells that have been shown to regenerate tissue and restore function. However, it is estimated that for an effective therapy, hundreds of millions of Schwann cells are needed, and current static and spinner flask methods cannot generate these clinical numbers. Therefore, this study utilizes control systems facilitated by stirred suspension bioreactors to monitor and maintain the pH and dissolved oxygen at levels that promote cell proliferation and survival. By adapting the current culture practices to scalable bioreactor platforms, we were able to control the dissolved oxygen creating new expansion protocols that enabled the bioreactor process to grow to clinical scale, producing 667 × 10 6 cells in a single 500 mL bioreactor in 7 days. Since individual injury is different in terms of complexity and severity, and therefore cell needs, by changing the available surface area in the bioreactor, this developed process is highly adjustable to meet the cell quantity needs for each individual treatment. Following the bioprocess, cells that were harvested from the microcarriers continue to express typical Schwann cell markers suggesting that they retain phenotypic stability. By increasing the production potential of skin-derived Schwann cells, this therapy is one step closer to the clinic with the hope for ultimately restoring function and improving quality of life to patients with neural injuries.

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Technical aspects of spinal cord injections for cell transplantation. Clinical and translational considerations

Cited by 53 publications

References 83 publications

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

Animal Models of Neurologic Disorders: A Nonhuman Primate Model of Spinal Cord Injury

Very High Resolution Ultrasound Imaging for Real-Time Quantitative Visualization of Vascular Disruption after Spinal Cord Injury

Control of dissolved oxygen significantly increases the yield of skin‐derived Schwann cells during expansion in stirred suspension bioreactors

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