Xenograft of Microencapsulated Sertoli Cells Reverses T1DM in NOD Mice by Inducing Neogenesis of Beta-Cells

Luca, Giovanni; Fallarino, Francesca; Calvitti, Mario; Mancuso, Francesca; Nastruzzi, Claudio; Arato, Iva; Falabella, G.; Grohmann, Ursula; Becchetti, Ennio; Puccetti, Paolo; Calafiore, Riccardo

doi:10.1097/tp.0b013e3181ffb9d2

Cited by 17 publications

(17 citation statements)

References 29 publications

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“…MC-SeC have been injected i.p. in a mouse model of type-1 diabetes, resulting in successful diabetes prevention and reversion in the absence of additional β cells or insulin therapy, through a TGF-β/IDO-mediated restoration of the systemic tolerance and induction of neogenesis of β cells [94,118]. Injection (i.p.)…”

Section: Pre-clinical Studies Using Microencapsulated Secmentioning

confidence: 99%

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Chiappalupi

Salvadori

Luca

et al. 2017

JFMK

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Duchenne muscular dystrophy (DMD) is a lethal X-linked pathology due to lack of dystrophin and characterized by progressive muscle degeneration, impaired locomotion and premature death. The chronic presence of inflammatory cells, fibrosis and fat deposition are hallmarks of DMD muscle tissue. Many different therapeutic approaches to DMD have been tested, including cell-based and gene-based approaches, exon skipping, induction of expression of the dystrophin paralogue, utrophin, and, most recently the application of the CASPR/Cas9 genome editing system. However, corticosteroid treatment remains the gold standard therapy, even if corticosteroids have shown multiple undesirable side effects. Sertoli cells (SeC) have long been known for their ability to produce immunomodulatory and trophic factors, and have been used in a plethora of experimental models of disease. Recently, microencapsulated porcine SeC (MC-SeC) injected intraperitoneally in dystrophic mice produced morphological and functional benefits in muscles thanks to their release into the circulation of anti-inflammatory factors and heregulin β1, a known inducer of utrophin expression, thus opening a new avenue in the treatment of DMD. In order to stress the potentiality of the use of MC-SeC in the treatment of DMD, here, we examine the principal therapeutic approaches to DMD, and the properties of SeC (either nude or encapsulated into alginate-based microcapsules) and their preclinical and clinical use. Finally, we discuss the potential and future development of this latter approach.Keywords: Duchenne muscular dystrophy; therapeutic approaches; Sertoli cell; muscle inflammation; myopathies; encapsulation; biomaterials Duchenne Muscular Dystrophy (DMD)Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy. Muscular dystrophies are a group of inherited muscle diseases characterized by mutations in specific genes and resulting in muscle degeneration, impaired locomotion and premature death [1,2]. DMD is an X-linked recessive pathology caused by mutations in the dystrophin gene (DMD) usually resulting in the complete absence of this protein. Dystrophin is an essential component of the dystrophin-associated protein complex (DAPC) at the sarcolemma, a complex that ensures the structural and functional integrity of the myofibers during contraction representing a mechanical link between the intracellular cytoskeleton and the extracellular matrix. Absence of dystrophin or other components of the DAPC compromises the integrity of the DAPC itself leading to a susceptibility of myofibers to degeneration

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Section: Pre-clinical Studies Using Microencapsulated Secmentioning

confidence: 99%

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Chiappalupi

Salvadori

Luca

et al. 2017

JFMK

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“…As compared with naked cells or islet cells encapsulated without contrast material, neither magnetocapsules 1 , X-caps 2 nor fluorocapsules 3 is anticipated to interfere with cell viability and C-peptide secretion by islet cells. Because of their ability to function as an oxygen sink, fluorocapsules can be expected to improve cell function 3 .…”

Section: Anticipated Resultsmentioning

confidence: 99%

“…Because of their ability to function as an oxygen sink, fluorocapsules can be expected to improve cell function 3 .…”

Section: Anticipated Resultsmentioning

confidence: 99%

“…Adding a contrast agent to the capsule instead of into cells may potentially bypass toxicity issues that can result from direct cell labeling 17 . The addition of either iron oxide, barium and bismuth sulfate, or perfluorocarbons does not reduce cell viability and C-peptide secretion of islet cells 1–3 . Viability of encapsulated cells is determined mainly by the host microenvironment of the engrafted site.…”

Section: Introductionmentioning

confidence: 91%

“…Immunoprotective microencapsulation is particularly attractive, as it both abrogates the need for chronic immunosuppressive therapy and opens up the possibility of immunoisolating xenogenic grafts 2,3 . To date, encapsulation has shown clinical potential for insulin 4,5 and parathyroid 6 hormone replacement therapy.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of magnetic resonance–, X-ray– and ultrasound-visible alginate microcapsules for immunoisolation and noninvasive imaging of cellular therapeutics

et al. 2011

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Cell therapy has the potential to treat or cure a wide variety of diseases. Non-invasive cell tracking techniques are, however, necessary to translate this approach to the clinical setting. This protocol details methods to create microcapsules that are visible by X-ray, ultrasound (US ) or magnetic resonance (MR) for the encapsulation and immunoisolation of cellular therapeutics. Three steps are generally used to encapsulate cellular therapeutics in an alginate matrix: (i) droplets of cell-containing liquid alginate are extruded, using an electrostatic generator, through a needle tip into a solution containing a dissolved divalent cation salt to form a solid gel; (ii) the resulting gelled spheres are coated with polycations as a cross-linker; and (iii) these complexes are then incubated in a second solution of alginate to form a semipermeable membrane composed of an inner and an outer layer of alginate. The microcapsules can be rendered visible during the first step by adding contrast agents to the primary alginate layer. Such contrast agents include superparamagnetic iron oxide for detection by 1H MR imaging (MRI); the radiopaque agents barium or bismuth sulfate for detection by X-ray modalities; or perfluorocarbon emulsions for multimodal detection by 19F MRI, X-ray and US imaging. The entire synthesis can be completed within 2 h.

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Therapeutic Applications of Encapsulated Cells

Acarregui

Orive

Pedraz

et al. 2013

Methods in Molecular Biology

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The synergy of some promising advances in the fields of cell therapy and biomaterials together with improvements in the fabrication of more refined and tailored microcapsules for drug delivery have triggered the progress of cell encapsulation technology. Cell microencapsulation involves immobilizing the transplanted cells within a biocompatible scaffold surrounded by a membrane in attempt to isolate the cells from the host immune attack and enhance or prolong their function in vivo. This technology represents one strategy which aims to overcome the present difficulties related to local and systemic controlled release of drugs and growth factors as well as to organ graft rejection and thus the requirements for use of immunomodulatory protocols or immunosuppressive drugs. This chapter gives an overview of the current situation of cell encapsulation technology as a controlled drug delivery system, and the essential requirements of the technology, some of the therapeutic applications, the challenges, and the future directions under investigation are highlighted.

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Xenograft of Microencapsulated Sertoli Cells Reverses T1DM in NOD Mice by Inducing Neogenesis of Beta-Cells

Cited by 17 publications

References 29 publications

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Employment of Microencapsulated Sertoli Cells as a New Tool to Treat Duchenne Muscular Dystrophy

Synthesis of magnetic resonance–, X-ray– and ultrasound-visible alginate microcapsules for immunoisolation and noninvasive imaging of cellular therapeutics

Therapeutic Applications of Encapsulated Cells

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