Immunosuppression

Porrett, Paige M.; Hashmi, S.; Shaked, Abraham

doi:10.1016/j.cld.2014.05.012

Cited by 13 publications

(5 citation statements)

References 160 publications

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“…21,23,[50][51][52][53][54] Long term immunosuppression can increase the risk of infection and malignancy, as reported by clinical studies. [68][69][70] To enhance the beneficial effect of the grafts despite the limited survival rate, equipping the cells with cDNA of additional therapeutic substance that can be released from the graft is a viable approach. Conopeptides, small peptides produced by marine cone snails, with unique affinity to various receptors within the CNS, have become a major focus for new drug development.…”

Section: Discussionmentioning

confidence: 99%

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Analgesic effect of recombinant GABAergic precursors releasing ω-conotoxin MVIIA in a model of peripheral nerve injury in rats

2022

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Development of chronic pain has been attributed to dysfunctional GABA signaling in the spinal cord. Direct pharmacological interventions on GABA signaling are usually not very efficient and often accompanied by side effects due to the widespread distribution of GABA receptors in CNS. Transplantation of GABAergic neuronal cells may restore the inhibitory potential in the spinal cord. Grafted cells may also release additional analgesic peptides by means of genetic engineering to further enhance the benefits of this approach. Conopeptides are ideal candidates for recombinant expression using cell-based strategies. The omega-conopeptide MVIIA is in clinical use for severe pain marketed as FDA approved Prialt in the form of intrathecal injections. The goal of this study was to develop transplantable recombinant GABAergic cells releasing conopeptide MVIIA and to evaluate the analgesic effect of the grafts in a model of peripheral nerve injury-induced pain. We have engineered and characterized the GABAergic progenitors expressing MVIIA. Recombinant and nonrecombinant cells were intraspinally injected into animals after the nerve injury. Animals were tested weekly up to 12 weeks for the presence of hypersensitivity, followed by histochemical and biochemical analysis of the tissue. We observed beneficial effects of the grafted cells in reducing hypersensitivity in all grafted animals, especially potent in the recombinant group. The level of pain-related cytokines was reduced in the grafted animals and correlation between these pain markers and actual behavior was indicated. This study demonstrated the feasibility of recombinant cell transplantation in the management of chronic pain.

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Section: Discussionmentioning

confidence: 99%

“…21,23,50–54 Long term immunosuppression can increase the risk of infection and malignancy, as reported by clinical studies. 68–70 To enhance the beneficial effect of the grafts despite the limited survival rate, equipping the cells with cDNA of additional therapeutic substance that can be released from the graft is a viable approach.…”

Section: Discussionmentioning

confidence: 99%

Analgesic effect of recombinant GABAergic precursors releasing ω-conotoxin MVIIA in a model of peripheral nerve injury in rats

2022

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“…The application of autologous cell therapy would be beneficial over allogeneic stem cell therapy, as it does not require the use of immunosuppressive agents. This would be beneficial for the patient, as an immunosuppressive regimen makes them more vulnerable to infections ( Porrett et al, 2014 ; Halter et al, 2015 ). Moreover, for intra-arterial MABs transplantation, inflammation is required for skeletal muscle engraftment, which might be impaired by the use of immunosuppressive agents ( Cossu et al, 2015 ).…”

Section: Mitochondrial Myopathiesmentioning

confidence: 99%

Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle

et al. 2021

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This article will review myogenic cell transplantation for congenital and acquired diseases of skeletal muscle. There are already a number of excellent reviews on this topic, but they are mostly focused on a specific disease, muscular dystrophies and in particular Duchenne Muscular Dystrophy. There are also recent reviews on cell transplantation for inflammatory myopathies, volumetric muscle loss (VML) (this usually with biomaterials), sarcopenia and sphincter incontinence, mainly urinary but also fecal. We believe it would be useful at this stage, to compare the same strategy as adopted in all these different diseases, in order to outline similarities and differences in cell source, pre-clinical models, administration route, and outcome measures. This in turn may help to understand which common or disease-specific problems have so far limited clinical success of cell transplantation in this area, especially when compared to other fields, such as epithelial cell transplantation. We also hope that this may be useful to people outside the field to get a comprehensive view in a single review. As for any cell transplantation procedure, the choice between autologous and heterologous cells is dictated by a number of criteria, such as cell availability, possibility of in vitro expansion to reach the number required, need for genetic correction for many but not necessarily all muscular dystrophies, and immune reaction, mainly to a heterologous, even if HLA-matched cells and, to a minor extent, to the therapeutic gene product, a possible antigen for the patient. Finally, induced pluripotent stem cell derivatives, that have entered clinical experimentation for other diseases, may in the future offer a bank of immune-privileged cells, available for all patients and after a genetic correction for muscular dystrophies and other myopathies.

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“…However, the shortage of organs available for transplantation makes it hard to meet the existing demands, 1 and many patients die while waiting for a transplantable organ 2 . Although HLA matching between organs of donors and recipients is performed during transplantation, most transplanted recipients have to persevere with lifelong immunosuppressant drug regimens, which might result in a risk of life‐threatening infections 3–8 . Haematopoietic stem cell transplantation (HSCT) has been successfully used to induce tolerance during organ transplantation by the establishment of mixed haematopoietic chimerism.…”

Section: Introductionmentioning

confidence: 99%

“…2 Although HLA matching between organs of donors and recipients is performed during transplantation, most transplanted recipients have to persevere with lifelong immunosuppressant drug regimens, which might result in a risk of life-threatening infections. [3][4][5][6][7][8] Haematopoietic stem cell transplantation (HSCT) has been successfully used to induce tolerance during organ transplantation by the establishment of mixed haematopoietic chimerism. In addition, HSCT has been widely applied to the treatment of certain types of blood cancer and immune disorders.…”

Section: Introductionmentioning

confidence: 99%

A novel inducible haematopoietic cell‐depleting mouse model for chimeric complementation of blood cells

Cao

et al. 2023

Cell Proliferation

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Haematopoietic stem cell transplantation (HSCT) is widely used in regenerative medicine. HSCT can be used not only to treat certain types of blood cancer and immune disorders but also to induce immune tolerance in organ transplantation. However, the inadequacy of HSCs available for transplantation is still a major hurdle for clinical applications. Here, we established a novel inducible haematopoietic cell-depleting mouse model and tested the feasibility of using chimeric complementation to regenerate HSCs and their progeny cells. Large populations of syngeneic and major histocompatibility-mismatched haematopoietic cells were successfully regenerated by this model. The stable allogeneic chimeric mice maintained a substantial population of donor HSCs and Tregs, which indicated that the donor allogeneic HSCs successfully repopulated the recipient blood system, and the regenerated donor Tregs played essential roles in establishing immune tolerance in the allogeneic recipients. In addition, rat blood cells were detected in this model after xenotransplantation of rat whole bone marrow (BM) or Lin À BM cells. This mouse model holds promise for regenerating xenogeneic blood cells, including human haematopoietic cells.

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Immunosuppression

Cited by 13 publications

References 160 publications

Analgesic effect of recombinant GABAergic precursors releasing ω-conotoxin MVIIA in a model of peripheral nerve injury in rats

Analgesic effect of recombinant GABAergic precursors releasing ω-conotoxin MVIIA in a model of peripheral nerve injury in rats

Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle

A novel inducible haematopoietic cell‐depleting mouse model for chimeric complementation of blood cells

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