Intracerebroventricular Delivery of Human Umbilical Cord Mesenchymal Stem Cells as a Promising Therapy for Repairing the Spinal Cord Injury Induced by Kainic Acid

Nishida, Fabián; Villar, María Florencia Zappa; Zanuzzi, Carolina Natalia; Sisti, María Susana; Camiña, Agustina E.; Reggiani, Paula C.; Portiansky, Enrique Leo

doi:10.1007/s12015-019-09934-y

Cited by 13 publications

(12 citation statements)

References 61 publications

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“…WJ-MSC were used in many plethora of application. In neurology, WJ-MSCs are administered to patients with amyotrophic lateral sclerosis, multiple sclerosis, spinal cord injury as well acute and chronic stroke [88,97,98]. Research is also being conducted on WJ-MSC in neurological diseases in young patients with cerebral palsy, autism, traumatic brain damage and hypoxic-ischemic encephalopathy.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal Stromal Cells from Different Parts of Umbilical Cord: Approach to Comparison & Characteristics

Semenova

Grudniak

Machaj

et al. 2021

Stem Cell Rev and Rep

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Mesenchymal stromal/stem cells (MSCs) are a unique population of cells that play an important role in the regeneration potential of the body. MSCs exhibit a characteristic phenotype and are capable of modulating the immune response. MSCs can be isolated from various tissues such as: bone marrow, adipose tissue, placenta, umbilical cord and others. The umbilical cord as a source of MSCs, has strong advantages, such as no-risk procedure of tissue retrieval after birth and easiness of the MSCs isolation. As the umbilical cord (UC) is a complex organ and we decided to evaluate, whether the cells derived from different regions of umbilical cord show similar or distinct properties. In this study we characterized and compared MSCs from three regions of the umbilical cord: Wharton’s Jelly (WJ), the perivascular space (PRV) and the umbilical membrane (UCM). The analysis was carried out in terms of morphology, phenotype, immunomodulation potential and secretome. Based on the obtained results, we were able to conclude, that MSCs derived from distinct UC regions differ in their properties. According to our result WJ-MSCs have high and stabile proliferation potential and phenotype, when compare with other MSCs and can be treated as a preferable source of cells for medical application. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

“…The influence of MCP-1 on immunomodulation, including inhibition of immunoglobulin production by plasma cells and also influence on macrophage function, was emphasized [ 86 , 87 ]. Additionally, MCP-1 able to promote MSCs cellular migration process [ 85 , 88 ].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stromal Cells from Different Parts of Umbilical Cord: Approach to Comparison & Characteristics

Semenova

Grudniak

Machaj

et al. 2021

Stem Cell Rev and Rep

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show abstract

“…Nevertheless, in traumatic SCI that have a considerable prevalence in humans (Rupp, 2020) and in domestic animals (Smith & Jeffery, 2006) the use of IGF‐1 was barely tested. Although traumatic SCI phases are the same as for nontraumatic lesion (Nishida et al., 2020), events are occurring faster than in nontraumatic events. Depending on the level of the spine at which it occurs and the severity of the insult, traumatic SCI may cause symptoms ranging from pain to complete loss of motor and sensory functions beyond the level of the injury (Rosner, Avalos, Acosta, Liu, & Drazin, 2012).…”

Section: Discussionmentioning

confidence: 99%

Intracisternal IGF‐1 gene therapy abrogates kainic acid‐induced excitotoxic damage of the rat spinal cord

Nishida

Zanuzzi

Sisti

et al. 2020

Eur J of Neuroscience

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Development of alternative therapies for treating functional deficits after different neurological damages is a challenge in neuroscience. Insulin-like growth factor-1 (IGF-1) is a potent neurotrophic factor exerting neuroprotective actions in brain and spinal cord. It is used to prevent or treat injuries of the central nervous system using different administration routes in different animal models. In this study, we evaluated whether intracisternal (IC) route for IGF-1 gene therapy may abrogate or at least reduce the structural and behavioral damages induced by the intraparenchymal injection of kainic acid (KA) into the rat spinal cord. Experimental (Rad-IGF-1) and control (Rad-DsRed-KA) rats were evaluated using a battery of motor and sensory tests before the injection of the recombinant adenovector (day −3), before KA injection (day 0) and at every post-injection (pi) time point (days 1, 2, 3 and 7 pi). Histopathological changes and neuronal and glial counting were assessed. Pretreatment using IC delivery of RAd-IGF-1 improved animal's general condition and motor and sensory functions as compared to Rad-DsRed-KA-injected rats. Besides, IC Rad-IGF-1 therapy abrogated later spinal cord damage and reduced the glial response induced by KA as observed in Rad-DsRed-KA rats. We conclude that the IC route for delivering RAd-IGF-1 prevents KA-induced excitotoxicity in the spinal cord. K E Y W O R D S adenoviral gene therapy, intracisternal route, neurotoxicity, neurotrophic factor 3340 | NISHIDA et Al. How to cite this article: Nishida F, Zanuzzi CN, Sisti MS, et al. Intracisternal IGF-1 gene therapy abrogates kainic acid-induced excitotoxic damage of the rat spinal cord.

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“…It was shown that administration of MSCs reduces microglia and astroglia activation at the site of spinal cord injury. [ 183–186 ] In MSC‐treated SCI rats, the level of proinflammatory cytokines IL‐1 β , IL‐6, TNF‐ α was decreased, but anti‐inflammatory cytokines IL‐10 and IL‐12 were increased. [ 187,188 ]…”

Section: Experimental Attempts To Use Mesenchymal Stem Cells In the Tmentioning

confidence: 99%

Mesenchymal Stem Cells for Neurological Disorders

et al. 2021

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Neurological disorders are becoming a growing burden as society ages, and there is a compelling need to address this spiraling problem. Stem cell‐based regenerative medicine is becoming an increasingly attractive approach to designing therapies for such disorders. The unique characteristics of mesenchymal stem cells (MSCs) make them among the most sought after cell sources. Researchers have extensively studied the modulatory properties of MSCs and their engineering, labeling, and delivery methods to the brain. The first part of this review provides an overview of studies on the application of MSCs to various neurological diseases, including stroke, traumatic brain injury, spinal cord injury, multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, Parkinson's disease, and other less frequently studied clinical entities. In the second part, stem cell delivery to the brain is focused. This fundamental but still understudied problem needs to be overcome to apply stem cells to brain diseases successfully. Here the value of cell engineering is also emphasized to facilitate MSC diapedesis, migration, and homing to brain areas affected by the disease to implement precision medicine paradigms into stem cell‐based therapies.

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Intracerebroventricular Delivery of Human Umbilical Cord Mesenchymal Stem Cells as a Promising Therapy for Repairing the Spinal Cord Injury Induced by Kainic Acid

Cited by 13 publications

References 61 publications

Mesenchymal Stromal Cells from Different Parts of Umbilical Cord: Approach to Comparison & Characteristics

Mesenchymal Stromal Cells from Different Parts of Umbilical Cord: Approach to Comparison & Characteristics

Intracisternal IGF‐1 gene therapy abrogates kainic acid‐induced excitotoxic damage of the rat spinal cord

Mesenchymal Stem Cells for Neurological Disorders

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