Systemic immune modulation using chemokine receptor 7 expressing porcine Sertoli cells

Lee, Hak Mo; Lim, Hong Gook; Oh, Byoung Chol; Park, Chun Soo; Lee, Dong Sup; Lee, Jeong Ryul

doi:10.1111/j.1399-3089.2007.00435.x

Cited by 8 publications

(15 citation statements)

References 27 publications

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“…Evidence that SeC are primarily responsible for the successful survival and function of transplanted tissues was provided when SeC were co-transplanted with allogeneic Langerhans islets, showing that SeC were able to protect islets from rejection in the absence of immunosuppression [79]. Later, several experiments confirmed the ability of SeC to protect from immune destruction allogeneic and xenogeneic pancreatic islets [80,81], and other tissues, including xenogeneic adrenal chromaffin cells [82], allogeneic dopaminergic neurons [83], allogeneic and xenogeneic skin grafts [81,84], and allogeneic heart grafts [85]. The ability of SeC to protect xenogeneic pancreatic islets from rejection was demonstrated also in human patients, in a controversial study with respect to ethical issues.…”

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

confidence: 65%

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: Sertoli Cells: Multiple Roles For a Single Cell Typementioning

confidence: 65%

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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“…In one case, the injected SCs migrated into the mesenteric lymph nodes and spleen (Lee et al 2007a), suggesting that SCs may induce systemic immune tolerance through direct interaction with the recipient's immune cells within the lymphoid organs. This is further supported since, as compared to mice that did not receive SCs, lymphocytes isolated from spleens from mice that had been injected with SCs were found to have a significant decrease in proliferation rate after stimulation with allogeneic or xenogeneic cells.…”

Section: Sertoli Cell Influence On T-cell Responsesmentioning

confidence: 99%

“…Intravenous or intraperitoneal injection of SC led to prolonged survival of skin (Shamekh et al 2006, Lee et al 2007a) and heart (Lim et al 2009) grafts. In one case, the injected SCs migrated into the mesenteric lymph nodes and spleen (Lee et al 2007a), suggesting that SCs may induce systemic immune tolerance through direct interaction with the recipient's immune cells within the lymphoid organs.…”

Section: Sertoli Cell Influence On T-cell Responsesmentioning

confidence: 99%

“…SCs have also been shown to prolong survival of xenogeneic adrenal chromaffin cells (Sanberg et al 1996), xenogeneic neurons (Willing et al 1999), xenogeneic liver cells (Rahman et al 2005), allogeneic and xenogeneic skin grafts (Shamekh et al 2006, Lee et al 2007a, and allogeneic heart grafts (Lim et al 2009). The first report of SCs protecting other cells besides islets was by Sanberg et al (1996), where they co-transplanted rat SCs with bovine adrenal chromaffin cells into the rat brain.…”

Section: Co-transplantation Of Sertoli Cells With Other Tissuesmentioning

confidence: 99%

“…(Lee et al 2007a, Lim et al 2009) injection of SCs. A significant prolongation in the survival of skin (Shamekh et al 2006, Lee et al 2007a) and heart (Lim et al 2009) grafts was observed in mice that had received an injection of SCs. This is different from the previous studies, where SCs were co-transplanted with the protected allogeneic or xenogeneic tissues.…”

Section: Co-transplantation Of Sertoli Cells With Other Tissuesmentioning

confidence: 99%

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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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Cell-mediated Immunomodulation of Chemokine Receptor 7–expressing Porcine Sertoli Cells in Murine Heterotopic Heart Transplantation

Lim

Lee

et al. 2009

The Journal of Heart and Lung Transplantation

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Systemic immune modulation using chemokine receptor 7 expressing porcine Sertoli cells

Abstract: These results suggest that our new strategy to traffic SC to lymphoid organs using CCR7 is very effective and can be extended to traffic other immune modulatory cells or proteins to primary and secondary lymphoid structures to augment their therapeutic potential.

Cited by 8 publications

References 27 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

Immunoprotective Sertoli cells: making allogeneic and xenogeneic transplantation feasible

Cell-mediated Immunomodulation of Chemokine Receptor 7–expressing Porcine Sertoli Cells in Murine Heterotopic Heart Transplantation

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