Three‐yr follow‐up of a type 1 diabetes mellitus patient with an islet xenotransplant

Valdés-González, Rafael; White, David J.; Dorantes, Luis M; Terán, L; Garibay-Nieto, Guadalupe N.; Bracho-Blanchet, Eduardo; Dávila-Pérez, Roberto; Evia-Viscarra, María Lola; Ormsby, Christopher E.; Ayala-Sumuano, Jorge-Tonatiuh; Silva-Torres, M.L.; Ramírez-González, B

doi:10.1111/j.1399-0012.2007.00648.x

Cited by 34 publications

(29 citation statements)

References 23 publications

(24 reference statements)

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“…Histological analysis was performed on grafts removed from four patients after 3 years, and insulin and glucagon positive islet cells and mullerian inhibiting substance (a marker for SCs) positive SCs were identified within the grafts. The same group reported similar results in a more recent case, where an 18-year-old woman received an analogous transplant regimen (Valdes-Gonzalez et al 2007).…”

Section: Clinical Transplantation Of Porcine Sertoli Cellssupporting

confidence: 65%

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Mital¹,

Kaur²,

2010

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The testis as an immune-privileged site allows long-term survival of allogeneic and xenogeneic transplants. Testicular Sertoli cells (SCs) play a major role in this immunoprotection and have been used to create an ectopic immune-privileged environment that prolongs survival of co-transplanted allogeneic and xenogeneic cells, including pancreatic islets and neurons. Extended survival of such grafts testifies to the immunoprotective properties of SCs. However, there is still variability in the survival rates of the co-grafted cells and rarely are 100% of the grafts protected. This emphasizes the need to learn more about what is involved in creating the optimal immunoprotective milieu. Several parameters including organization of the SCs into tubule-like structures and the production of immunomodulatory factors by SCs, specifically complement inhibitors, cytokines, and cytotoxic lymphocyte inhibitors, are likely important. In addition, an intricate interplay between several of these factors may be responsible for providing the most ideal environment for protection of the co-transplants by SCs. In this review, we will also briefly describe a novel use for the immune-privileged abilities of SCs; engineering them to deliver therapeutic proteins for the treatment of diseases like diabetes and Parkinson's disease. In conclusion, further studies and more detailed analysis of the mechanisms involved in creating the immune-protective environment by SCs may make their application in co-transplantation and as engineered cells clinically feasible.

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Section: Clinical Transplantation Of Porcine Sertoli Cellssupporting

confidence: 65%

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Mital¹,

Kaur²,

2010

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“…Pancreatic islets were inserted together with neonatal porcine SeC in a porous chamber and placed subcutaneously in the anterior abdominal wall of young diabetic patients, without immunosuppressive treatment. The patients did not show any complications in a 7-years follow-up, and a half of the grafted patients significantly diminished their insulin doses [86,87]. Finally, SeC have been employed in different experimental models of diseases to take advantage of their release of trophic and anti-inflammatory factors (Table 2).…”

Section: Sertoli Cells: Multiple Roles For a Single Cell Typementioning

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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“…Sertoli cells were also able to enhance survival of islets graft in xenogeneic recipients [171173] . Finally, coencapsulated porcine islets and Sertoli cells were implanted into human subjects in a controversial Mexican clinical trial [8,174,175] . Some of the transplanted patients experienced reduction in their requirements for insulin therapy for up to 3 years.…”

Section: Controlling Inflammationmentioning

confidence: 99%

Survival of encapsulated islets: More than a membrane story

Barkai¹,

Rotem²,

Vos³

2016

WJT

114

109

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Three‐yr follow‐up of a type 1 diabetes mellitus patient with an islet xenotransplant

Cited by 34 publications

References 23 publications

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

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

Survival of encapsulated islets: More than a membrane story

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