Low immunogenicity of in vitro-expanded human neural cells despite high MHC expression

Odeberg, Jenny; Piao, Jinghua; Samuelsson, Eva‐Britt; Falci, Scott; Åkesson, Elisabet

doi:10.1016/j.jneuroim.2004.11.016

Cited by 75 publications

(60 citation statements)

References 30 publications

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“…The expression levels of CD80 and CD86 could also increase after passaging but are very low in primary tumors (17). Normal neurospheres, on the other hand, express MHC II molecules but are weakly immunogenic because of the low expression levels of costimulatory molecules (18). Therefore, it seems that GL261-NS have a peculiar set of expression of molecules highly relevant for immune recognition.…”

Section: Discussionmentioning

confidence: 99%

Neurospheres Enriched in Cancer Stem–Like Cells Are Highly Effective in Eliciting a Dendritic Cell–Mediated Immune Response against Malignant Gliomas

Pellegatta¹,

Poliani

Corno³

et al. 2006

Cancer Research

235

188

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Cancer stem-like cells (CSC) could be a novel target for cancer therapy, including dendritic cell (DC) immunotherapy. To address this, we developed experiments aimed at DC targeting of neurospheres (NS) from GL261 glioma cells because neurospheres can be enriched in CSC. We obtained murine neurospheres by growing GL261 cells in epidermal growth factor/basic fibroblast growth factor without serum. GL261-NS recapitulated important features of glioblastoma CSC and expressed higher levels of radial glia stem cell markers than GL261 cells growing under standard conditions (GL261 adherent cells, GL261-AC), as assessed by DNA microarray and real-time PCR. GL261-NS brain gliomas were highly infiltrating and more rapidly lethal than GL261-AC, as evidenced by survival analysis (P < 0.0001), magnetic resonance imaging and histology. DC from the bone marrow of syngeneic mice were then used for immunotherapy of GL261-NS and GL261-AC tumors. Strikingly, DC loaded with GL261-NS (DC-NS) cured 80% and 60% of GL261-AC and GL261-NS tumors, respectively (P < 0.0001), whereas DC-AC cured only 50% of GL261-AC tumors (P = 0.0022) and none of the GL261-NS tumors. GL261-NS expressed higher levels of MHC and costimulatory molecules (CD80 and CD86) than GL261-AC; the JAM assay indicated that DC-NS splenocytes had higher lytic activity than DC-AC splenocytes on both GL261-NS and GL261-AC, and immunohistochemistry showed that DC-NS vaccination was associated with robust tumor infiltration by CD8+ and CD4+ T lymphocytes. These findings suggest that DC targeting of CSC provides a higher level of protection against GL261 gliomas, a finding with potential implications for the design of clinical trials based on DC vaccination.

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Section: Discussionmentioning

confidence: 99%

Neurospheres Enriched in Cancer Stem–Like Cells Are Highly Effective in Eliciting a Dendritic Cell–Mediated Immune Response against Malignant Gliomas

Pellegatta¹,

Poliani

Corno³

et al. 2006

Cancer Research

235

188

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“…Under basal growth conditions the co-stimulatory molecules CD80/ B7.1, CD86/B7.2 and CD40 are also absent in both MSCs and NPCs (Odeberg et al, 2005;Tse et al, 2003). MSCs and NPCs fail to elicit a proliferative response when co-cultured with allogeneic mismatched peripheral blood mononuclear cells (PBMCs) (Laguna Goya et al, 2011;Odeberg et al, 2005;Tse et al, 2003). A single study investigating the immunogenicity of human NPCs in vitro, by one-way MLR with peripheral blood lymphocytes from human leukocyte antigen (HLA)-mismatched donors, shows than NPCs hold a low-but not negligible-immunogenic potential that is sufficient to activate peripheral lymphocytes.…”

Section: In Vitro Stem Cell Immunogenicitymentioning

confidence: 99%

Section: In Vitro Stem Cell Immunogenicitymentioning

confidence: 99%

How stem cells speak with host immune cells in inflammatory brain diseases

Pluchino

Cossetti

2013

Glia

110

109

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Advances in stem cell biology have raised great expectations that diseases and injuries of the central nervous system (CNS) may be ameliorated by the development of non-hematopoietic stem cell medicines. Yet, the application of adult stem cells as CNS therapeutics is challenging and the interpretation of some of the outcomes ambiguous. In fact, the initial idea that stem cell transplants work only via structural cell replacement has been challenged by the observation of consistent cellular signaling between the graft and the host. Cellular signaling is the foundation of coordinated actions and flexible responses, and arises via networks of exchanging and interacting molecules that transmit patterns of information between cells. Sustained stem cell graft-to-host communication leads to remarkable trophic effects on endogenous brain cells and beneficial modulatory actions on innate and adaptive immune responses in vivo, ultimately promoting the healing of the injured CNS. Among a number of adult stem cell types, mesenchymal stem cells (MSCs) and neural stem/precursor cells (NPCs) are being extensively investigated for their ability to signal to the immune system upon transplantation in experimental CNS diseases. Here, we focus on the main cellular signaling pathways that grafted MSCs and NPCs use to establish a therapeutically relevant cross talk with host immune cells, while examining the role of inflammation in regulating some of the bidirectionality of these communications. We propose that the identification of the players involved in stem cell signaling might contribute to the development of innovative, high clinical impact therapeutics for inflammatory CNS diseases.

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“…Indeed, human NSCs and newly formed astrocytes, but not neurons, suppressed lymphocyte stimulation to alloantigens, suggesting low risk for alloreaction and a role as immunomodulators. Despite these results, in accordance with providing evidence of NSCs low immunogenicity (Odeberg et al 2005) and ability to produce TGF-cytokine with a potent bystander effect on limpho/monocytes (Ubiali et al 2007), the presence of MHC class I and II molecules on hNSCs implies a risk for recognition by alloreactive T cells after transplantation, thus indicating a potential risk for immunological rejection due to MHC incompatibility and subsequent requirement of immunosuppressive treatment to avoid rejection. The disadvantages of using immunosuppressive treatment include an increased risk for opportunistic infections, toxic side effects and potential negative effects on donor cells.…”

Section: Neural Stem Cellsmentioning

confidence: 58%