Adipose-derived mesenchymal stromal cells from genetically modified pigs: immunogenicity and immune modulatory properties

Kumar, Gopal; Hara, Hidetaka; Long, Cassandra; Shaikh, Humza S.; Ayares, David; Cooper, D. K. C.; Ezzelarab, Mohamed

doi:10.3109/14653249.2011.651529

Cited by 28 publications

(28 citation statements)

References 39 publications

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“…Transplant of cells derived from another species [55], [56], another organism of the same species [57], seemingly inappropriate tissue origin [58], biochemically damaged/modified [59] and even genetically transfected cells [60] have all been attempted despite the developmental organisational hurdles believed by so many others [61]. The concept of ‘pluripotency’ has been heralded despite the consequences of potential teratomas [62].…”

Section: Discussionmentioning

confidence: 99%

Expansion of Multipotent Stem Cells from the Adult Human Brain

et al. 2013

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The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells.

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Section: Discussionmentioning

confidence: 99%

Expansion of Multipotent Stem Cells from the Adult Human Brain

et al. 2013

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“…For example, pigs expressing the immunoregulatory molecule CTLA4-Ig have been produced [24] [25], and anti-inflammatory agents have been shown to reduce the human T cell response to pig cells in vitro [16]. Our previous studies indicated that a large number of MSC can be effectively harvested from GTKO/CD46 pig fat tissue [26]. We have also shown that Gal expression was associated with increased human T cell responses to pig cells [27].…”

Section: Discussionmentioning

confidence: 99%

Human T cells upregulate CD69 after coculture with xenogeneic genetically-modified pig mesenchymal stromal cells

Andreyev

Chen

et al. 2013

Cellular Immunology

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Mesenchymal stromal cells (MSC) obtained from α1,3-galactosyltransferase gene knock-out pigs transgenic for the human complement-regulatory protein CD46 (GTKO/CD46 pMSC) suppress in vitro human anti-pig cellular responses as efficiently as allogeneic human MSC. We investigated the immunoregulatory effects of GTKO/CD46 pMSC on human CD4+ and CD8+ T cell proliferation in response to pig aortic endothelial cells (pAEC). pMSC efficiently suppressed T cell proliferation, which was associated with downregulation of granzyme B expression. No induction of CD4+CD25+Foxp3hi regulatory T cells or T cell apoptosis was documented. In correlation with T cell proliferation, CD25 expression was upregulated on T cells in response to pAEC but not to pMSC. In contrast, CD69 expression was upregulated on T cells in response to both pMSC and pAEC, which was associated with a significant increase in the phosphorylation of STAT5. GTKO/CD46 pMSC possibly regulate human T cell responses through modulation of CD69 expression and STAT5 signaling.

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“…73 When delivered in the absence of a scaffold, galactosyl epitope knock-out (Gal-KO) pig MSCs attenuated immune response and improved bone regeneration. 68,106 This strategy could serve to improve the host response to native ECM scaffolds. Allogenic and xenogenic ECM materials, even after decellularization, are capable of eliciting an immune response due to the presence of ECM proteins, which have been shown to stimulate the migration of neutrophils and macrophages.…”

Section: Biological Propertiesmentioning

confidence: 99%

Functional Augmentation of Naturally-Derived Materials for Tissue Regeneration

Allen

Priddy

et al. 2014

Ann Biomed Eng

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Tissue engineering strategies have utilized a wide spectrum of synthetic and naturally-derived scaffold materials. Synthetic scaffolds are better defined and offer the ability to precisely and reproducibly control their properties, while naturally-derived scaffolds typically have inherent biological and structural properties that may facilitate tissue growth and remodeling. More recently, efforts to design optimized biomaterial scaffolds have blurred the line between these two approaches. Naturally-derived scaffolds can be engineered through the manipulation of intrinsic properties of the pre-existing backbone (e.g., structural properties), as well as the addition of controllable functional components (e.g., biological properties). Chemical and physical processing techniques used to modify structural properties of synthetic scaffolds have been tailored and applied to naturally-derived materials. Such strategies include manipulation of mechanical properties, degradation, and porosity. Furthermore, bio-functional augmentation of natural scaffolds via incorporation of exogenous cells, proteins, peptides, or genes has been shown to enhance functional regeneration over endogenous response to the material itself. Moving forward, the regenerative mode of action of naturally-derived materials requires additional investigation. Elucidating such mechanisms will allow for the determination of critical design parameters to further enhance efficacy and capitalize on the full potential of naturally-derived scaffolds.

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Adipose-derived mesenchymal stromal cells from genetically modified pigs: immunogenicity and immune modulatory properties

Cited by 28 publications

References 39 publications

Expansion of Multipotent Stem Cells from the Adult Human Brain

Expansion of Multipotent Stem Cells from the Adult Human Brain

Human T cells upregulate CD69 after coculture with xenogeneic genetically-modified pig mesenchymal stromal cells

Functional Augmentation of Naturally-Derived Materials for Tissue Regeneration

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