Therapeutic Potential of Human Adipose-Derived Stem Cells in Neurological Disorders

Chang, Keun-A; Lee, Jun-Ho; Suh, Yoo‐Hun

doi:10.1254/jphs.14r10cp

Cited by 44 publications

(31 citation statements)

References 57 publications

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“…So in order to test whether AdMSCs-IFN-ß (gene therapy) were able to improve the reported therapeutic effects of non-transduced AdMSCs (cell therapy) (Karussis and Kassis, 2008;Chang et al, 2014;Schwerk et al, 2015;Bonafede et al, 2016), we investigated their efficacy in two experimental models of MS: the RR and CP-EAE, as there is much controversy over whether the effects of autologous MSCs are indistinguishable (Kassis et al, 2013) or not (Zhang et al, 2014) from the effects induced by allogeneic MSCs in ameliorating the clinical score of EAE.…”

Section: Discussionmentioning

confidence: 99%

Gene therapy with mesenchymal stem cells expressing IFN‐ß ameliorates neuroinflammation in experimental models of multiple sclerosis

Marín-Bañasco

Benabdellah

Melero-Jerez

et al. 2017

British J Pharmacology

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*Equally contributed. BACKGROUND AND PURPOSERecombinant IFN-ß is one of the first-line treatments in multiple sclerosis (MS), despite its lack of efficacy in some patients. In this context, mesenchymal stem cells (MSCs) represent a promising therapeutic alternative due to their immunomodulatory properties and multipotency. Moreover, by taking advantage of their pathotropism, these cells can be genetically modified to be used as carriers for delivering or secreting therapeutic drugs into injured tissues. Here, we report the therapeutic effect of systemic delivery of adipose-derived MSCs (AdMSCs), transduced with the IFN-β gene, into mice with experimental autoimmune encephalomyelitis (EAE). EXPERIMENTAL APPROACHRelapsing-remitting and chronic progressive EAE were induced in mice. Cells were injected i.v. Disease severity, inflammation and tissue damage were assessed clinically, by flow cytometry of spleens and histopathological evaluation of the CNS respectively. KEY RESULTSGenetic engineering did not modify the biological characteristics of these AdMSCs (morphology, growth rate, immunophenotype and multipotency). Furthermore, the transduction of IFN-ß to AdMSCs maintained and, in some cases, enhanced the functional properties of AdMSCs by ameliorating the symptoms of MS in EAE models and by decreasing indications of peripheral and central neuro-inflammation. CONCLUSION AND IMPLICATIONSGene therapy was found to be more effective than cell therapy in ameliorating several clinical parameters in both EAE models, presumably due to the continuous expression of IFN-β. Furthermore, it has significant advantages over AdMSC therapy, and also over systemic IFN-ß treatment, by providing long-term expression of the cytokine at therapeutic concentrations and reducing the frequency of injections, while minimizing dose-limiting side effects.

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Section: Discussionmentioning

confidence: 99%

Gene therapy with mesenchymal stem cells expressing IFN‐ß ameliorates neuroinflammation in experimental models of multiple sclerosis

Marín-Bañasco

Benabdellah

Melero-Jerez

et al. 2017

British J Pharmacology

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“…Despite these obstacles, numerous studies have demonstrated improvements in learning and memory by transplanting neural stem cells to the brains of rodents modeling AD [139][140][141][142][143][144][145][146][147][148] . In addition, transplantation of adipose-derived stem cells to mouse models of AD have shown restoration of memory deficits [149][150][151] and human umbilical cord-derived MSCs that have been differentiated to neuron-like cells also improve cognitive function in AD mouse models [152,153] . The various stem cell types used in transplantation studies in rodent models of AD are summarized in [154,155] .…”

Section: Stem Cell Transplantation For Neurological Disordersmentioning

confidence: 99%

Applications of the Keap1–Nrf2 system for gene and cell therapy

Pomeshchik

Leinonen

Malm

et al. 2015

Free Radical Biology and Medicine

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“…Several preclinical stroke studies have shown beneficial effects following transplantation of stem cells derived from various sources, including embryonic tissue [1], adult bone marrow [2], adipose [3], and umbilical cord blood (UCB) [4, 5]. Amongst these, UCB cells offer several advantages because they are more readily available and have no associated graft-versus-host reactions [6].…”

Section: Introductionmentioning

confidence: 99%

Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function

Huang

Liu

et al. 2017

Stem Cell Res Ther

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BackgroundHuman umbilical cord blood (hUCB) cell therapy is a promising treatment for ischemic stroke. The effects of hyperacute stem cell transplantation on cerebrovascular function in ischemic stroke are, however, not well understood. This study evaluated the effects of hyperacute intraarterial transplantation of hUCB mononuclear cells (MNCs) on cerebrovascular function in stroke rats using serial magnetic resonance imaging (MRI).MethodsHUCB MNCs or vehicle were administered to stroke rats via the internal carotid artery immediately after reperfusion at 60 min following ischemia onset. Lesion volumes were longitudinally evaluated by MRI on days 0, 2, 14, and 28 after stroke, accompanied by behavioral tests. Cerebral blood flow (CBF) and cerebrovascular reactivity were measured by perfusion MRI and CO2 functional MRI (fMRI) at 28 days post-stroke; corresponding vascular morphological changes were also detected by immunohistology in the same animals.ResultsWe found that CBF to the stroke-affected region at 28 days was improved (normalized CBF value: 1.41 ± 0.30 versus 0.49 ± 0.07) by intraarterial transplantation of hUCB MNCs in the hyperacute stroke phase, compared to vehicle control. Cerebrovascular reactivity within the stroke-affected area, measured by CBF fMRI, was also increased (35.2 ± 3.5% versus 12.8 ± 4.3%), as well as the corresponding cerebrovascular density. Some engrafted cells appeared with microvascular-like morphology and stained positive for von Willebrand Factor (an endothelial cell marker), suggesting they differentiated into endothelial cells. Some engrafted cells also connected to host endothelial cells, suggesting they interacted with the host vasculature. Compared to the vehicle group, infarct volume at 28 days in the stem cell treated group was significantly smaller (160.9 ± 15.7 versus 231.2 ± 16.0 mm3); behavioral deficits were also markedly reduced by stem cell treatment at day 28 (19.5 ± 1.0% versus 30.7 ± 4.7% on the foot fault test; 68.2 ± 4.6% versus 86.6 ± 5.8% on the cylinder test). More tissue within initial perfusion-diffusion mismatch was rescued in the treatment group.ConclusionsIntraarterial hUCB MNC transplantation during the hyperacute phase of ischemic stroke improved cerebrovascular function and reduced behavioral deficits and infarct volume.

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Therapeutic Potential of Human Adipose-Derived Stem Cells in Neurological Disorders

Cited by 44 publications

References 57 publications

Gene therapy with mesenchymal stem cells expressing IFN‐ß ameliorates neuroinflammation in experimental models of multiple sclerosis

Gene therapy with mesenchymal stem cells expressing IFN‐ß ameliorates neuroinflammation in experimental models of multiple sclerosis

Applications of the Keap1–Nrf2 system for gene and cell therapy

Intraarterial transplantation of human umbilical cord blood mononuclear cells in hyperacute stroke improves vascular function

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