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Raghunath J.,University College London | Sutherland J.,The Anthony Nolan Research Institute | Salih V.,University College London | Mordan N.,University College London | And 2 more authors.
Journal of Plastic, Reconstructive and Aesthetic Surgery | Year: 2010

Introduction: The associated morbidity from the acquisition of mesenchymal stem cells (MSC) from the bone marrow has led to the investigation of alternative stem cell sources. We propose that such cells may be isolated from non-mobilised blood and demonstrate their differentiation into a chondrocytic lineage. This safe and abundant source of cells may be useful for tissue engineering cartilage. Method: Peripheral blood mononuclear cells (PBMC) were isolated from healthy adults and cultured in RPMI medium supplemented with serum. The non-adherent and adherent cells were analysed for cell surface marker expression of CD14, CD34, CD133, CD105 and CD45 by flow cytometry. Adherent cells were also cultured on glass slides in chondrogenic media and analysed for the expression of collagen I and II on day 14 of culture. Results: The adherent cells were fibroblastic in morphology and were confluent on day 14. The non-adherent and adherent cell populations were shown to have distinct profiles by flow cytometry. The adherent cells were positive for CD105 and CD14 and also expressed collagen I and II precursors when cultured in chondrogenic media. Conclusion: Blood-acquired mesenchymal progenitor cells (BMPCs) can be isolated from non-mobilised blood. These unique cells are CD105+ and CD14+ and have chondrogenic differentiation capacity. BMPC may provide a potential source of MPC for tissue engineering applications. © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons.

Cox S.T.,The Anthony Nolan Research Institute | Laza-Briviesca R.,The Anthony Nolan Research Institute | Madrigal J.A.,The Anthony Nolan Research Institute | Madrigal J.A.,University College London | And 2 more authors.
Tissue Antigens | Year: 2014

Description of a novel RAET1E/ULBP4 allele characterized by sequence-based typing and cloning: RAET1E*011 © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Laza-Briviesca R.,The Anthony Nolan Research Institute | Saudemont A.,The Anthony Nolan Research Institute | Saudemont A.,University College London | Madrigal J.A.,The Anthony Nolan Research Institute | And 2 more authors.
International Journal of Immunogenetics | Year: 2015

In this study, we have characterized two novel polymorphism of the 5' promoter sequence of MICA gene, MICA-P13 and MICA-P14, by sequence-based typing and cloning. © 2015 John Wiley & Sons Ltd.

Cox S.T.,The Anthony Nolan Research Institute | Laza-Briviesca R.,The Anthony Nolan Research Institute | Pearson H.,The Anthony Nolan Research Institute | Soria B.,Andalusian Center for Molecular Biology and Regenerative Medicine | And 8 more authors.
European Journal of Immunology | Year: 2015

NK cells play a key role in innate elimination of virally infected or neoplastic cells but they can be circumvented by immunoevasive mechanisms enabling viral spread or tumor progression. Engagement of the NKG2D activating receptor with soluble forms of its ligand is one such mechanism of inducing NK cell hyporesponsiveness. Interestingly, this immunoevasive strategy among others is described at the maternal-fetal interface where tolerance of the semi-allogeneic fetus is required to allow successful human pregnancy. Understanding of maternal-fetal tolerance is increasing but mechanisms preventing alloreactivity of fetal immune cells against the maternal host are less well understood. The study of umbilical cord blood has enabled insight of the fetal immune system, which appears immature and inert. We have found that soluble NKG2D ligands (sNKG2DLs) are present in cord blood plasma (CBP) and associate with adult NK cell hyporesponsiveness demonstrated by reduced CD107a expression and secretion of IFN-γ upon stimulation. The capacity of NK cells to kill K562 cells or proliferate was also reduced by incubation with CBP; however, physical removal of sNKG2DL from CBP restored K562 lytic function and NKG2D expression. Therefore, our results strongly suggest sNKG2DLs are expressed in CBP as a mechanism of fetal-maternal tolerance in human pregnancy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cox S.T.,The Anthony Nolan Research Institute | Arrieta-Bolanos E.,The Anthony Nolan Research Institute | Arrieta-Bolanos E.,University College London | Arrieta-Bolanos E.,University of Costa Rica | And 6 more authors.
Human Immunology | Year: 2013

NK cell cytolysis of infected or transformed cells can be mediated by engagement of the activating immunoreceptor NKG2D with one of eight known ligands (MICA, MICB and RAET1E-N) and is essential for innate immunity. As well as diversity of NKG2D ligands having the same function, allelic polymorphism and ethnic diversity has been reported. We previously determined HLA class I allele and haplotype frequencies in Kolla South American Indians who inhabit the northwest provinces of Argentina, and were found to have a similar restricted allelic profile to other South American Indians and novel alleles not seen in other tribes. In our current study, we characterized retinoic acid early transcription-1 (RAET1) alleles by sequencing 58 unrelated Kolla people. Only three of six RAET1 ligands were polymorphic. RAET1E was most polymorphic with five alleles in the Kolla including an allele we previously described, RAET1E*009 (allele frequency (AF) 5.2%). Four alleles of RAET1L were also found and RAET1E*002 was most frequent (AF=78%). Potential functional diversity only affected RAET1E and RAET1L, which were in linkage disequilibrium indicating a selective advantage. The results suggest that limited RAET1 polymorphism in the Kolla was not detrimental to human survival but still necessary and may affect disease susceptibility or severity. © 2013.

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