Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics

Jiménez, Antonio; Fung, Henry C.; Christopherson, Kent W.

doi:10.1111/j.1537-2995.2011.03375.x

Cited by 3 publications

(4 citation statements)

References 89 publications

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“…Current knowledge of the immunological and functional aspects of xeno(allo)-cellular transplantation of stem cells, HSC, and umbilical cord blood is used in, e.g. cardiomyopathy, diabetes, liver failure, neural, endocrine and pulmonary diseases, bone regeneration and immunotherapy [ 9 – 20 , 25 – 28 ]. Allotransplantation is promising for parathyroid and thymus reconstruction [ 21 , 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…By understanding the cellular components and mechanisms by which HSCT is either enhanced or suppressed it will then be possible to design therapeutic strategies to improve rates of engraftment that will have a positive impact on immune reconstitution post-HSCT. In this review we focus primarily on allogeneic hematopoietic stem cell transplantation (allo-HSCT), the current challenges associated with allo-HSCT, and some developing strategies to improve engraftment in this setting [ 16 , 25 ].…”

Section: Discussionmentioning

confidence: 99%

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Experimental immunology Xenotransplantation of human cultured parathyroid progenitor cells into mouse peritoneum does not induce rejection reaction

Nawrot¹,

Woźniewicz²,

Szmidt³

et al. 2014

cejoi

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IntroductionParathyroid progenitor cells devoid of immunogenic antigens were used for human allotransplantation. Although there were many potential reasons for the expiry of transplant activity in humans, we decided to exclude a subclinical form of rejection reaction, and test the rejection reaction in an animal model.Material and methodsExperiments were carried out on 40 conventional male mice in their third month of life. The animals were housed in groups of 10 per cage in 4 cages with fitted water dispensers and fed a conventional diet based on standard pellet food. They were divided into four groups of 10 animals each, three experimental groups and one control group. Identified progenitor cells were stored in a cell bank. After testing the phenotype, viability, and absence of immunogenic properties, the cells were transplanted into mouse peritoneum cavity.ResultsAnimals were observed for 9 weeks. At 9 weeks of observation, the mean serum PTH concentration in the experimental groups was 2.0-2.5 pg/ml, while in the control group it did not exceed 1.5 pg/ml. The immunohistochemical assays demonstrated that millions of viable cells with a phenotype identical to the endocrine cells had survived in the peritoneum. Histologic specimens from different internal organs stained for PTH revealed positive cells labelled with anti-PTH Ab in the intestinal lamina, brain, liver, and spleen.ConclusionsIn the present paper we have demonstrated that xenotransplantation may be used as a model for an explanation of the immunogenic properties of cells generated from postnatal organs for regenerative therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Experimental immunology Xenotransplantation of human cultured parathyroid progenitor cells into mouse peritoneum does not induce rejection reaction

Nawrot¹,

Woźniewicz²,

Szmidt³

et al. 2014

cejoi

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“…Therefore, ex vivo priming of UCB HSC with these molecules may promote homing and engraftment of the HSC (69, 70). Inhibition of the membrane bound extracellular peptidase (CD26), which cleaves SDF-1, also enhances long-term engraftment in UCB CD34 + cells in NOD/SCID/beta 2 microglobulin null mice (71, 72). Fucosylation of ligands expressed on HSC is also required for their interaction with selectins expressed in the BM microvasculature.…”

Section: Improving Engraftment and Immune Reconstitution Following Ucmentioning

confidence: 99%

Improving Engraftment and Immune Reconstitution in Umbilical Cord Blood Transplantation

2014

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Umbilical cord blood (UCB) is an important source of hematopoietic stem cells (HSC) for allogeneic transplantation when HLA-matched sibling and unrelated donors (MUD) are unavailable. Although the overall survival results for UCB transplantation are comparable to the results with MUD, UCB transplants are associated with slow engraftment, delayed immune reconstitution, and increased opportunistic infections. While this may be a consequence of the lower cell dose in UCB grafts, it also reflects the relative immaturity of cord blood. Furthermore, limited cell numbers and the non-availability of donor lymphocyte infusions currently prevent the use of post-transplant cellular immunotherapy to boost donor-derived immunity to treat infections, mixed chimerism, and disease relapse. To further develop UCB transplantation, many strategies to enhance engraftment and immune reconstitution are currently under investigation. This review summarizes our current understanding of engraftment and immune recovery following UCB transplantation and why this differs from allogeneic transplants using other sources of HSC. It also provides a comprehensive overview of promising techniques being used to improve myeloid and lymphoid recovery, including expansion, homing, and delivery of UCB HSC; combined use of UCB with third-party donors; isolation and expansion of natural killer cells, pathogen-specific T cells, and regulatory T cells; methods to protect and/or improve thymopoiesis. As many of these strategies are now in clinical trials, it is anticipated that UCB transplantation will continue to advance, further expanding our understanding of UCB biology and HSC transplantation.

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“…In mouse models, inhibition of the membrane bound extracellular peptidase dipeptidyl peptidase-4 (DPP4) (CD26), which cleaves SDF-1, enhances long-term engraftment in UCB CD34 + cells in NOD/SCID/beta 2 microglobulin null mice [120,121]. Alternatively, fucosylation (the addition of a fucose) of ligands expressed on HSC may enhance engraftment.…”

Section: Improving Delivery and Homing Of Hscmentioning

confidence: 99%

Current Strategies to Improve Engraftment in Cord Blood Transplantation

Danby

Rocha²

2014

J Stem Cell Res Ther

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Umbilical cord blood (UCB) remains an important alternative source of hematopoietic stem cells (HSC) for allogeneic transplantation when suitable HLA-matched donors are unavailable. Cord blood (CB) offers many benefits including rapid availability, absence of risk to the donor, and a low incidence of graft-versus-host disease. However, although the overall survival of patients receiving unrelated CB transplants is comparable to using other HSC sources, UCB transplantation is associated with delayed engraftment and poor immune reconstitution, particularly in adults. While this is partly due to the lower cell dose in UCB grafts, it may also reflect the relative immaturity of cord blood. Therefore, many different strategies to enhance hematopoietic engraftment following UCB transplantation are currently under investigation. This article will review the latest techniques including improved collection, HLAmatching, homing and expansion of CB, and the use of double CB grafts, third-party donors, and accessory cells. As many of these methods are now in clinical trials, it is anticipated that UCB transplantation will continue to improve, further expanding our understanding of CB biology and HSC transplantation.

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Cellular therapies supplement: strategies for improving transplant efficiency in the context of cellular therapeutics

Cited by 3 publications

References 89 publications

Experimental immunology Xenotransplantation of human cultured parathyroid progenitor cells into mouse peritoneum does not induce rejection reaction

Experimental immunology Xenotransplantation of human cultured parathyroid progenitor cells into mouse peritoneum does not induce rejection reaction

Improving Engraftment and Immune Reconstitution in Umbilical Cord Blood Transplantation

Current Strategies to Improve Engraftment in Cord Blood Transplantation

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