Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury

Kalani, Anuradha; Chaturvedi, Pankaj; Kamat, Pradip K.; Maldonado, Claudio; Bauer, Philip M.; Joshua, Irving G.; Tyagi, Suresh C.; Tyagi, Neetu

doi:10.1016/j.biocel.2016.09.002

Cited by 200 publications

(147 citation statements)

References 46 publications

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“…To the best of the authors' knowledge, six different studies have examined effects of EVs in ischemic stroke models, most in rats and one in mice [112][113][114][116][117][118]. In the first rat study, Chopp and colleagues [113] intravenously applied MSC-EVs in a model of transient intraluminal middle cerebral artery occlusion.…”

Section: Preclinical Studies Using Evs In Animal Models Associated Wimentioning

confidence: 99%

Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke

Doeppner

Bähr

Hermann

et al. 2017

Stem Cells Translational Medicine

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Despite recent advances in stroke therapy, current therapeutic concepts are still limited. Thus, additional therapeutic strategies are in order. In this sense, the transplantation of stem cells has appeared to be an attractive adjuvant tool to help boost the endogenous regenerative capacities of the brain. Although transplantation of stem cells is known to induce beneficial outcome in (preclinical) stroke research, grafted cells do not replace lost tissue directly. Rather, these transplanted cells like neural progenitor cells or mesenchymal stem cells act in an indirect manner, among which the secretion of extracellular vesicles (EVs) appears to be one key factor. Indeed, the application of EVs in preclinical stroke studies suggests a therapeutic role, which appears to be noninferior in comparison to the transplantation of stem cells themselves. In this short review, we highlight some of the recent advances in the field of EVs as a therapeutic means to counter stroke. STEM CELLS TRANSLATIONAL MEDICINE 2017;6:2044-2052 SIGNIFICANCE STATEMENTDespite recent success in therapeutic approaches against stroke, especially in the field of endovascular therapy, additional therapeutic means are still in order. In this sense, the application of extracellular vesicles might be an interesting tool to induce post-ischemic neuroregeneration, overcoming the limitations and risks of stem cell transplantation themselves.

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Section: Preclinical Studies Using Evs In Animal Models Associated Wimentioning

confidence: 99%

Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke

Doeppner

Bähr

Hermann

et al. 2017

Stem Cells Translational Medicine

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“…BECDEs were isolated from mouse brain endothelial cell line (bEnd.3) as described previously (Kalani et al, 2014a)(Kalani et al, 2016) with some modifications. Briefly, bEnd.3 cell culture conditioned media was ultracentrifuged at 1,40,000x g at 4°C for 3 h after following two centrifugations at 3,000x g and 10,000x g, respectively.…”

Section: Methodsmentioning

confidence: 99%

Dementia-like pathology in type-2 diabetes: A novel microRNA mechanism

Kalani

Chaturvedi

Maldonado

et al. 2017

Molecular and Cellular Neuroscience

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Although type-2 diabetes (T2D) has been reported to increase the risk of cognitive dysfunction and dementia, the underlying mechanisms remain unclear. Dementia-like pathology is attributed to the accumulation of cellular prion protein (PrPc) which plays a role in cognitive dysfunction. However, its involvement and regulation in diabetic dementia-like pathology is not well understood. Using T2D db/db (leptin receptor knockout) mice subjected to object recognition and Y-maze behavioral tests, we determined that short-term memory was compromised and that the mice displayed abrupt spontaneous behaviour compared to db/m control mice. MicroRNA analysis using qRT2-PCR array demonstrated a significant reduction in the transcript expression of microRNA-146a (miR-146a) in the brain of T2D db/db mice as compared to db/m controls. The sequence matching tools validated the binding of miR-146a to a conserved domain of the PrPc gene. Administration of mouse brain endothelial cell-derived exosomes (BECDEs) loaded with miR-146a into the brain’s ventricle of T2D db/db mice attenuated brain PrPc levels and restored short-term memory function though not significant. Also, we observed hyperphosphorylation of tau through decreased expression of glycogen synthase kinase-3 in T2D db/db brains that regulates microtubule organization and memory function. We conclude that underexpression of miR-146a upregulates PrPc production in T2D db/db mice and the delivery of BECDEs loaded with a miR-146a can down regulate PrPc levels and restore short term memory function.

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“…The anti‐inflammatory effects of curcumin‐primed and curcumin‐encapsulated exosomes have been confirmed in various inflammatory diseases such as a brain tumor model (Zhuang et al, ), ischemia‐reperfusion (IR) injury (Kalani et al, ), ischemic stroke (Tian et al, ), various cancer models (Aqil et al, ; Osterman et al, ; Wang et al, ) and a septic shock cell culture model (Sun et al, ; Vashisht, Rani, Kumar Onteru, & Singh, ). Singh et al studied the effects of CUR‐EXO on proinflammatory cytokine gene (interleukin‐1β [IL‐1β], tumor necrosis factor‐α [TNF‐α], and interleukin‐6 [IL‐6]) expression in lipopolysaccharide (LPS; 1 μg/ml)‐treated buffalo granulosa cells.…”

Section: Impact Of Curcumin On Proinflammatory Cytokine Gene Expressionmentioning

confidence: 96%

Therapeutic use of curcumin‐encapsulated and curcumin‐primed exosomes

Oskouie

Moghaddam

Butler³

et al. 2018

Journal Cellular Physiology

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Curcumin, the bioactive pigment of turmeric which has polyphenolic‐hydrophobic components, has been used for the treatment of a variety of diseases. However, due to its insignificant intestinal‐liver metabolism, low stability, quick systemic elimination and its hydrophobic property with low solubility, curcumin has limited bioavailability. Exosomes are nanovesicles (30–100 nm) released from diverse cell types into extracellular and, ultimately, into bio‐fluids in a tightly regulated manner. Exosomes are capable of transferring lipids, proteins, RNAs and DNAs, both with and without direct cell‐to‐cell contact. Curcumin‐encapsulated exosomes are highly bioavailable, soluble and safe, and can reach high concentrations in the blood; they, therefore, have therapeutic potential without toxic effects and immune stimulation. Thus, curcumin‐encapsulated exosomes could be superior to other synthetic nanoparticles as a carrier of curcumin. The aim of the current review is to offer an overview of the in vitro, in vivo and clinical studies pertaining to the role of curcumin‐primed and curcumin‐encapsulated exosomes in the treatment of cancer, oxidative stress, brain disorders, cholesterol, and endothelial dysfunction.

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Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury

Cited by 200 publications

References 46 publications

Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke

Concise Review: Extracellular Vesicles Overcoming Limitations of Cell Therapies in Ischemic Stroke

Dementia-like pathology in type-2 diabetes: A novel microRNA mechanism

Therapeutic use of curcumin‐encapsulated and curcumin‐primed exosomes

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