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Dudakov J.A.,Sloan Kettering Cancer Center | Dudakov J.A.,Monash Immunology and Stem Cell Laboratories MISCL | Van Den Brink M.R.M.,Sloan Kettering Cancer Center
Best Practice and Research: Clinical Haematology | Year: 2011

Cytoreductive conditioning regimes designed to allow for successful allogeneic hematopoietic stem cell transplantation (allo-HSCT) paradoxically are also detrimental to recovery of the immune system in general but lymphopoiesis in particular. Post-transplant immune depletion is particularly striking within the T cell compartment which is exquisitely sensitive to negative regulation, evidenced by the profound decline in thymic function with age. As a consequence, regeneration of the immune system remains a significant unmet clinical need. Over the past decade studies have revealed several promising therapeutic strategies to address ineffective lymphopoiesis and post-transplant immune deficiency. These include the use of cytokines such as IL-7, IL-12 and IL-15; growth factors and hormones like keratinocyte growth factor (KGF), insulin-like growth factor (IGF)-1 and growth hormone (GH); adoptive transfer of ex vivo-generated precursor T cells (pre-T) and sex steroid ablation (SSA). Moreover, recently several novel approaches have been proposed to generate whole thymii ex vivo using stem cell technologies and bioscaffolds. Increasingly, however, when transferred to the clinic, these strategies alone are not sufficient to restore thymopoiesis in all patients leading to the potential of combination strategies as a way to reign in non-responders. Synergistic enhancement in combination may be due to differential targets may therefore be effective in improving clinical outcomes in the transplant settings as well as in other lymphopenic states induced by high dose chemotherapy/radiation therapy or HIV, and may also be useful in improving responses to vaccination and augmenting anti-tumor immunotherapy. © 2011 Elsevier Ltd. All rights reserved. Source


Dickinson H.,Monash Immunology and Stem Cell Laboratories MISCL | Dickinson H.,Monash Institute of Medical Research | Milton P.,Monash Immunology and Stem Cell Laboratories MISCL | Jenkin G.,Monash Immunology and Stem Cell Laboratories MISCL | Jenkin G.,Monash Institute of Medical Research
Cytotechnology | Year: 2012

The bone marrow represents the most common source from which to isolate mesenchymal stem cells (MSCs). MSCs are capable of differentiating into tissues of the three primary lineages and have the potential to enhance repair in damaged organs through the principals of regenerative medicine. Given the ease withwhichMSCsmay be isolated fromdifferent species the aim of this study was to isolate and characterize putative bone marrow derived MSCs from the spiny mouse, Acomys cahirinus.MSCswere isolated fromthe spiny mouse in a traditional manner, and based on plastic adherence, morphology, colony forming unitfibroblast assays and functional assessment (adipogenic, osteogenic and chondrogenic differentiation potential) a population of putative mesenchymal stemcells fromthe compact bone of the spinymouse have been isolated and characterized. Such methodological approaches overcome the lack of species-specific antibodies for the spiny mouse and could be employed for other species where the cost of generating species-specific antibodies is not warranted. © Springer Science+Business Media B.V. 2012. Source

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