Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation

Pathak, Shiva; Regmi, Shobha; Gupta, Biki; Poudel, Bijay Kumar; Pham, Tung Thanh; Kim, Jae‐Ryong; Park, Pil-Hoon; Yong, Chul Soon; Kim, Jong Oh; Bae, Young Kyung; Kim, Sang Kyoon; Jeong, Jee–Heon

doi:10.1021/acsami.6b07897

Cited by 24 publications

(14 citation statements)

References 68 publications

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“…For example, curcumin was chemically modified and conjugated to a thermo-responsive elastin-like polypeptide (ELP) as an injectable depot for sustained, local delivery of curcumin to treat neuroinflammation (Sinclair et al ., 2013). A curcumin-loaded polymeric microsphere was also developed as an interventional strategy to overcome apoptosis associated with pancreatic islets transplantation (Pathak et al ., 2016). Nanocarrier systems (hydrogels, polymeric nanoparticles, liposomes and self-assembling nanofibres) might be promising strategies to improve drug bioavailability, prolong systemic circulation and, possibly, incorporate other therapeutic agents to realise a multi-targeted synergistic effect (Joshi et al ., 2013).…”

Section: Discussionmentioning

confidence: 99%

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Xiao¹,

Ding²,

Fernandez³

et al. 2017

eCM

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Current non-surgical treatments for lumbar radiculopathy [e.g. epidural steroids and Tumour necrosis factor-α (TNF-α) antagonists] are neither effective nor safe. As a non-toxic natural product, curcumin possesses an exceptional anti-inflammatory profile. We hypothesised that curcumin alleviates lumbar radiculopathy by attenuating neuroinflammation, oxidative stress and nociceptive factors. In a dorsal root ganglion (DRG) culture, curcumin effectively inhibited TNF-α-induced neuroinflammation, in a dose-dependent manner, as shown by mRNA and protein expression of IL-6 and COX-2. Such effects might be mediated via protein kinase B (AKT) and extracellular signal regulated kinase (ERK) pathways. Also, a similar effect in combating TNF-α-induced neuroinflammation was observed in isolated primary neurons. In addition, curcumin protected neurons from TNF-α-triggered excessive reactive oxygen species (ROS) production and cellular apoptosis and, accordingly, promoted mRNA expression of the anti-oxidative enzymes haem oxygenase-1, catalase and superoxide dismutase-2. Intriguingly, electronic von Frey test suggested that intraperitoneal injection of curcumin significantly abolished ipsilateral hyperalgesia secondary to disc herniation in mice, for up to 2 weeks post-surgery. Such in vivo pain alleviation could be attributed to the suppression, observed in DRG explant culture, of TNF-α-elicited neuropeptides, such as substance P and calcitonin gene-related peptide. Surprisingly, micro-computed tomography (µCT) data suggested that curcumin treatment could promote disc height recovery following disc herniation. Alcian blue/picrosirius red staining confirmed that systemic curcumin administration promoted regeneration of extracellular matrix proteins, visualised by presence of abundant newly-formed collagen and proteoglycan content in herniated disc. Our study provided pre-clinical evidence for expediting this natural, non-toxic pleiotropic agent to become a new and safe clinical treatment of radiculopathy.

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Section: Discussionmentioning

confidence: 99%

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Xiao¹,

Ding²,

Fernandez³

et al. 2017

eCM

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“…In an attempt to address the setbacks associated with these encapsulation materials, the congregation of microspheres containing suppressive materials with or around these islets may provide a solution. Microspheres are specialized structures comprised from thin layers of cross-linked polymers, which can then be optimized for porosity to suit the desired cellular effect ( 173 , 174 ). Because this method relies less on a bulky shell, microspheres offer the flexibility to address larger issues such as the cellular microenvironment, both within and outside the capsule.…”

Section: Role Of Free Radicals and Pro-inflammatory Mediators Involvementioning

confidence: 99%

“…Because this method relies less on a bulky shell, microspheres offer the flexibility to address larger issues such as the cellular microenvironment, both within and outside the capsule. For example, the congregation of curcumin, an anti-apoptotic drug containing free radical scavenging capabilities, with the polymer poly(lactic-co-glycolic acid) to form heterospheroids can decrease oxidative stress and bolster insulin release in rat islets when used as an encapsulation material ( 174 ). This technique allows for a localized release of the redox-modulating drug directly at the site of transplantation without degradation in circulation.…”

Section: Role Of Free Radicals and Pro-inflammatory Mediators Involvementioning

confidence: 99%

Redox-Dependent Inflammation in Islet Transplantation Rejection

Barra

Tse

2018

Front. Endocrinol.

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Type 1 diabetes is an autoimmune disease that results in the progressive destruction of insulin-producing pancreatic β-cells inside the islets of Langerhans. The loss of this vital population leaves patients with a lifelong dependency on exogenous insulin and puts them at risk for life-threatening complications. One method being investigated to help restore insulin independence in these patients is islet cell transplantation. However, challenges associated with transplant rejection and islet viability have prevented long-term β-cell function. Redox signaling and the production of reactive oxygen species (ROS) by recipient immune cells and transplanted islets themselves are key players in graft rejection. Therefore, dissipation of ROS generation is a viable intervention that can protect transplanted islets from immune-mediated destruction. Here, we will discuss the newly appreciated role of redox signaling and ROS synthesis during graft rejection as well as new strategies being tested for their efficacy in redox modulation during islet cell transplantation.

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“…Procurement of donor male Sprague-Dawley rats, isolation of pancreatic islets, and preparation of ICCs were performed by using methods reported previously (20). Experimental rats were housed under specific pathogen-free conditions in an animal care center of Yeungnam University.…”

Section: Isolation Of Pancreatic Islets and Preparation Of Engineeredmentioning

confidence: 99%

“…Cell viability and functionality were assessed by using methods reported previously (20,21). Viability was assessed by using a Live/Dead Assay kit (Molecular Probes, Eugene, OR, USA) per manufacturer instructions.…”

Section: Assessment Of Viability and Functionalitymentioning

confidence: 99%

Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes

et al. 2017

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An alternative route for pancreatic islet transplantation is the subcutaneous space; however, inadequate vascularization in the subcutaneous space limits the availability of oxygen and nutrients to the subcutaneously transplanted islets, which leads to the development of a necrotic core in the islets, thereby causing islet dysfunction. Thus, we aimed to prevent the early apoptosis of pancreatic islets after transplantation into subcutaneous space by preparing islet clusters of appropriate size. We prepared fully functional islet cell clusters (ICCs) by using the hanging-drop technique. We optimized the size of ICCs on the basis of viability and functionality after culture in an hypoxic environment. We transplanted ICCs into the subcutaneous space of diabetic mice and evaluated the viability of the islets at the transplantation site. In an hypoxic environment, ICCs exhibited improved viability and functionality compared with control islets. ICCs, upon transplantation into the hypoxic subcutaneous space of diabetic mice, showed better glycemic control compared with control islets. Live/dead imaging of the islets after retrieval from the transplanted area revealed significantly reduced apoptosis in ICCs. Transplantation of ICCs may be an attractive strategy to prevent islet cell apoptosis that results from nonimmune-mediated physiologic stress at the transplantation site.-Pathak, S., Regmi, S., Gupta, B., Pham, T. T., Yong, C. S., Kim, J. O., Yook, S., Kim, J.-R., Park, M. H., Bae, Y. K., Jeong, J.-H. Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes.

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Hybrid Congregation of Islet Single Cells and Curcumin-Loaded Polymeric Microspheres as an Interventional Strategy to Overcome Apoptosis Associated with Pancreatic Islets Transplantation

Cited by 24 publications

References 68 publications

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Curcumin alleviates lumbar radiculopathy by reducing neuroinflammation, oxidative stress and nociceptive factors

Redox-Dependent Inflammation in Islet Transplantation Rejection

Engineered islet cell clusters transplanted into subcutaneous space are superior to pancreatic islets in diabetes

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