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hESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation.

Heuer A, Kirkeby A, Pfisterer U, Jönsson ME, Parmar M - Exp. Neurol. (2016)

Bottom Line: Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system.Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments.The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.

No MeSH data available.


Related in: MedlinePlus

Graft rejection response.Overview of characterisation of graft rejection of human to rat xenografts in fully immune-competent rat hosts over the time-course of 18 weeks post-engraftment. All rats were engrafted in parallel with the rats that were inoculated. Time-points for assessment of the immune and inflammation responses were 2 weeks (n = 3), 6 weeks (n = 2) and 18 weeks (n = 2) post transplantation. No graft was detected via staining for human NCAM (A–C) later than the 2 week time-point. Inflammation and immune responses were strongest at the early time-point (2 weeks) and somewhat dampened at the last time-point of assessment (18 weeks). The respective infiltration of immune cells were visualized using antibodies against microglia (Ox42, D–E), T-helper cells (G–I), T-cells (J–L), MHC-class I (M–O), and MHC-class II (P–R). Scalebar = 200 μM. The rejection seen in H9-hESC grafts in fully immune-competent hosts demonstrates the capability of these cells to elicit an immune response as well as the need and validity of the neonatal desensitisation approach.
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f0015: Graft rejection response.Overview of characterisation of graft rejection of human to rat xenografts in fully immune-competent rat hosts over the time-course of 18 weeks post-engraftment. All rats were engrafted in parallel with the rats that were inoculated. Time-points for assessment of the immune and inflammation responses were 2 weeks (n = 3), 6 weeks (n = 2) and 18 weeks (n = 2) post transplantation. No graft was detected via staining for human NCAM (A–C) later than the 2 week time-point. Inflammation and immune responses were strongest at the early time-point (2 weeks) and somewhat dampened at the last time-point of assessment (18 weeks). The respective infiltration of immune cells were visualized using antibodies against microglia (Ox42, D–E), T-helper cells (G–I), T-cells (J–L), MHC-class I (M–O), and MHC-class II (P–R). Scalebar = 200 μM. The rejection seen in H9-hESC grafts in fully immune-competent hosts demonstrates the capability of these cells to elicit an immune response as well as the need and validity of the neonatal desensitisation approach.

Mentions: In contrast, naïve rats (n = 7) that were engrafted in parallel using the same pre-differentiated H9-hESCs but received no form of immune-suppression showed a rapid rejection of the transplants within 6 weeks post engraftment (Fig. 2, D; Fig. 3 A-R). The appropriate immune reaction to the engrafted cells was accompanied by an early infiltration of microglia as well as a large amount of CD8 positive T-cells infiltrating the entire transplant. There was an abundance of MHC-class I and II positive cells and graft rejection was completed within 6 weeks post transplantation. The immune response was somewhat dampened after 18 weeks corresponding to the completed rejection of the foreign tissue. This demonstrates that the hESC-derived cells as such are immunogenic and are able to trigger an appropriate immune response, thereby leading to a rapid rejection of the transplant.


hESC-derived neural progenitors prevent xenograft rejection through neonatal desensitisation.

Heuer A, Kirkeby A, Pfisterer U, Jönsson ME, Parmar M - Exp. Neurol. (2016)

Graft rejection response.Overview of characterisation of graft rejection of human to rat xenografts in fully immune-competent rat hosts over the time-course of 18 weeks post-engraftment. All rats were engrafted in parallel with the rats that were inoculated. Time-points for assessment of the immune and inflammation responses were 2 weeks (n = 3), 6 weeks (n = 2) and 18 weeks (n = 2) post transplantation. No graft was detected via staining for human NCAM (A–C) later than the 2 week time-point. Inflammation and immune responses were strongest at the early time-point (2 weeks) and somewhat dampened at the last time-point of assessment (18 weeks). The respective infiltration of immune cells were visualized using antibodies against microglia (Ox42, D–E), T-helper cells (G–I), T-cells (J–L), MHC-class I (M–O), and MHC-class II (P–R). Scalebar = 200 μM. The rejection seen in H9-hESC grafts in fully immune-competent hosts demonstrates the capability of these cells to elicit an immune response as well as the need and validity of the neonatal desensitisation approach.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4920671&req=5

f0015: Graft rejection response.Overview of characterisation of graft rejection of human to rat xenografts in fully immune-competent rat hosts over the time-course of 18 weeks post-engraftment. All rats were engrafted in parallel with the rats that were inoculated. Time-points for assessment of the immune and inflammation responses were 2 weeks (n = 3), 6 weeks (n = 2) and 18 weeks (n = 2) post transplantation. No graft was detected via staining for human NCAM (A–C) later than the 2 week time-point. Inflammation and immune responses were strongest at the early time-point (2 weeks) and somewhat dampened at the last time-point of assessment (18 weeks). The respective infiltration of immune cells were visualized using antibodies against microglia (Ox42, D–E), T-helper cells (G–I), T-cells (J–L), MHC-class I (M–O), and MHC-class II (P–R). Scalebar = 200 μM. The rejection seen in H9-hESC grafts in fully immune-competent hosts demonstrates the capability of these cells to elicit an immune response as well as the need and validity of the neonatal desensitisation approach.
Mentions: In contrast, naïve rats (n = 7) that were engrafted in parallel using the same pre-differentiated H9-hESCs but received no form of immune-suppression showed a rapid rejection of the transplants within 6 weeks post engraftment (Fig. 2, D; Fig. 3 A-R). The appropriate immune reaction to the engrafted cells was accompanied by an early infiltration of microglia as well as a large amount of CD8 positive T-cells infiltrating the entire transplant. There was an abundance of MHC-class I and II positive cells and graft rejection was completed within 6 weeks post transplantation. The immune response was somewhat dampened after 18 weeks corresponding to the completed rejection of the foreign tissue. This demonstrates that the hESC-derived cells as such are immunogenic and are able to trigger an appropriate immune response, thereby leading to a rapid rejection of the transplant.

Bottom Line: Neonatal injections in rat pups using human fetal brain cells have been shown to desensitise the host to accept human tissue grafts as adults, whilst not compromising their immune system.Here, we show that differentiated human embryonic stem cells (hESCs) can be used for desensitisation to achieve long-term graft survival of human stem cell-derived neurons in a xenograft setting, surpassing the time of conventional pharmacological immune-suppressive treatments.The use of hESCs for desensitisation opens up for a widespread use of the technique, which will be of great value when performing pre-clinical evaluation of stem cell-derived neurons in animal models.

View Article: PubMed Central - PubMed

Affiliation: Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg Neuroscience Center, Lund University, Lund, Sweden; Lund Stem Cell Center, Lund University, Lund, Sweden.

No MeSH data available.


Related in: MedlinePlus