Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment

Fernández-Susavila, Héctor; Bugallo-Casal, Ana; Castillo, José; Campos, Francisco

doi:10.3389/fneur.2019.00908

Cited by 36 publications

(23 citation statements)

References 103 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Implantation of modified bone marrow-derived mesenchymal stem cells (SB623) transiently transfected with the human Notch-1 intracellular domain in a patient with stable chronic stroke is safe and is accompanied by improvements in clinical outcomes [61]. It is now well established that there is no engraftment of MSCs in the brain after intravenous administration and the recovery effects observed in some ischemic animal models are mediated by factors secreted by MSCs [62]. Recently, extracellular vesicles released by MSCs or NSCs are recognized as effective in vivo.…”

Section: Discussionmentioning

confidence: 99%

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Dong

Tian

et al. 2020

Stem Cell Res Ther

View full text Add to dashboard Cite

Recently, extensive researches about stem cell-based therapies for ischemic stroke have been published; our review evaluated the efficacy and safety of stem cell-based therapies for ischemic stroke. Our review was registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42019135805. Two independent observers searched PubMed, EMBASE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials), and Web of Science (Science Citation Index Expanded) for relevant studies up to 31 May 2019. We included clinical trials which compared efficacy outcomes (measured by National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), or Barthel index (BI)) and safety outcomes (such as death and adverse effects) between the stem cell-based therapies and control in ischemic stroke. We performed random effect meta-analysis using Review Manager 5.3. Our review included nine randomized controlled trials (RCTs) and seven non-randomized studies (NRSs), involving 740 participants. Stem cell-based therapies were associated with better outcomes measured by NIHSS (mean difference (MD) − 1.63, 95% confidence intervals (CI) − 2.73 to − 0.53, I 2 =60%) and BI (MD 14.68, 95% CI 1.12 to 28.24, I 2 = 68%) in RCTs, and by BI (MD 6.40, 95% CI 3.14 to 9.65, I 2 = 0%) in NRSs. However, the risk of bias was high and the efficacy outcomes of RCTs were high heterogeneity. There was no significant difference in mortality between the stem cell group and the control group. Fever, headache, and recurrent stroke were the most frequently reported adverse effects. Our review shows that stem cell-based therapies can improve the neurological deficits and activities of daily living in patients with ischemic stroke.

show abstract

Section: Discussionmentioning

confidence: 99%

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Dong

Tian

et al. 2020

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…Studies in animal models of stroke have shown that MSC treatment has beneficial effects on stroke recovery; however, contradictory results have also been reported [ 16 ]. The majority of in vitro and in vivo studies have been performed on rodent and human BM-MSCs, while human-derived ASCs are less studied [ 15 ]. Here, ASCs were cocultured on inserts with SH-SY5Y- and hiPSC-neurons after OGD for 24 or 72 h. The results showed that ASC coculture increased cell viability and decreased cytotoxicity and cell death in both cell models.…”

Section: Discussionmentioning

confidence: 99%

“…Transplantation of mesenchymal stem cells (MSCs) represents a new potential therapeutic strategy for stroke [ 15 ]. In previous in vivo animal studies, transplantation of MSCs has been shown to promote functional recovery and reduce lesion size [ 16 , 17 ], and these cells have already been utilized in clinical phase studies with varying results [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons

Juntunen

Hagman

Moisan³

et al. 2020

Stem Cells International

View full text Add to dashboard Cite

Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different in vitro human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied. In the present study, SH-SY5Y human neuroblastoma cells and human induced pluripotent stem cells (hiPSCs) were differentiated into neurons, cultured under OGD conditions (1% O2) for 24 h, and subjected to a reperfusion period for 24 or 72 h. After OGD, ASCs were cocultured with neurons on inserts for 24 or 72 h to study the neuroprotective potential of ASCs. The effect of OGD and ASC coculture on the viability, apoptosis, and proliferation of and axonal damage to neuronal cells was studied. The results showed that OGD conditions induced cytotoxicity and apoptosis of SH-SY5Y- and hiPSC-derived neurons, although more severe damage was detected in SH-SY5Y-derived neurons than in hiPSC-derived neurons. Coculture with ASCs was protective for neurons, as the number of dead ASC-cocultured neurons was lower than that of control cells, and coculture increased the proliferation of both cell types. To conclude, we developed in vitro human cell-based stroke models in SH-SY5Y- and hiPSC-derived neurons. This was the first time hiPSCs were used to model stroke in vitro. Since OGD had different effects on the studied cell types, this study highlights the importance of using several cell types in in vitro studies to confirm the outcomes of the study. Here, ASCs exerted a neuroprotective effect by increasing the proliferation and decreasing the death of SH-SY5Y- and hiPSC-derived neurons after OGD.

show abstract

“…Moreover, the administration of fasudil-loaded liposomes under occlusion ameliorated the injury associated with reperfusion by rt-PA. 164) Xu et al developed a multifunctional formulation called "nanoplatelets" for sequential selective delivery of rt-PA and neuroprotectant to ischemic sites. 165) Those neuroprotectant-loaded nanoparticles with thrombin-cleavable Tat peptide-coupled rt-PA can deliver rt-PA to thrombi and enhance migration to ischemic sites.…”

Section: Ischemic Strokementioning

confidence: 99%

“…The current status and details of exogenous stem cell transplantation are summarized in other reviews. 166,167) Endogenous NSC activation is receiving increased attention because it does not require the processing of living cells. Some therapeutic systems have been developed in combination with DDS techniques.…”

Section: Ischemic Strokementioning

confidence: 99%

Recent Strategies for Targeted Brain Drug Delivery

2020

View full text Add to dashboard Cite

Because the brain is the most important human organ, many brain disorders can cause severe symptoms. For example, glioma, one type of brain tumor, is progressive and lethal, while neurodegenerative diseases cause severe disability. Nevertheless, medical treatment for brain diseases remains unsatisfactory, and therefore innovative therapies are desired. However, the development of therapies to treat some cerebral diseases is difficult because the blood-brain barrier (BBB) or blood-brain tumor barrier prevents drugs from entering the brain. Hence, drug delivery system (DDS) strategies are required to deliver therapeutic agents to the brain. Recently, brain-targeted DDS have been developed, which increases the quality of therapy for cerebral disorders. This review gives an overview of recent brain-targeting DDS strategies. First, it describes strategies to cross the BBB. This includes BBB-crossing ligand modification or temporal BBB permeabilization. Strategies to avoid the BBB using local administration are also summarized. Intrabrain drug distribution is a crucial factor that directly determines the therapeutic effect, and thus it is important to evaluate drug distribution using optimal methods. We introduce some methods for evaluating drug distribution in the brain. Finally, applications of brain-targeted DDS for the treatment of brain tumors, Alzheimer's disease, Parkinson's disease, and stroke are explained.

show abstract

Adult Stem Cells and Induced Pluripotent Stem Cells for Stroke Treatment

Cited by 36 publications

References 103 publications

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

Stem cell-based therapies for ischemic stroke: a systematic review and meta-analysis of clinical trials

In Vitro Oxygen-Glucose Deprivation-Induced Stroke Models with Human Neuroblastoma Cell- and Induced Pluripotent Stem Cell-Derived Neurons

Recent Strategies for Targeted Brain Drug Delivery

Contact Info

Product

Resources

About