Limits...
Mesenchymal stromal cells do not increase the risk of viral reactivation nor the severity of viral events in recipients of allogeneic stem cell transplantation.

Lucchini G, Dander E, Pavan F, Di Ceglie I, Balduzzi A, Perseghin P, Gaipa G, Algarotti A, Introna M, Rambaldi A, Rovelli A, Biondi A, Biagi E, D'Amico G - Stem Cells Int (2012)

Bottom Line: No patient presented severe form of infection.Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity.In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

View Article: PubMed Central - PubMed

Affiliation: Clinica Pediatrica, Università degli Studi di Milano Bicocca, Ospedale San Gerardo, 20900 Monza, Italy.

ABSTRACT
Mesenchymal stromal cells (MSC) are tested in clinical trials to treat graft versus host disease (GvHD) after stem cell transplantation (SCT). In vitro studies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts) receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

No MeSH data available.


Related in: MedlinePlus

Frequency of CMV-specific T cells, secreting interferon gamma (IFN-γ) in response to a cocktail of CMV-specific peptides, as measured by ELISPOT assay in two patients reactivating CMV after having received mesenchymal stem cells (MSCs) for the treatment of steroid refractory graft versus host disease. Dotted lines on top of the panels indicate Ganciclovir administration. In the upper panel overall GvHD grading according to NIH criteria is shown. In the central panel Cytomegalovirus (CMV) reactivation trend as measured in copies/milliliter of peripheral blood (PB) is shown. In the lower panel the number of CMV-specific IFN-γ producing cells in relation to MSC infusions as measured in IFN-γ spots/100.000 peripheral blood-mononucleated cells (PBMC) is shown. Black arrows indicate MSC infusions.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3369546&req=5

fig1: Frequency of CMV-specific T cells, secreting interferon gamma (IFN-γ) in response to a cocktail of CMV-specific peptides, as measured by ELISPOT assay in two patients reactivating CMV after having received mesenchymal stem cells (MSCs) for the treatment of steroid refractory graft versus host disease. Dotted lines on top of the panels indicate Ganciclovir administration. In the upper panel overall GvHD grading according to NIH criteria is shown. In the central panel Cytomegalovirus (CMV) reactivation trend as measured in copies/milliliter of peripheral blood (PB) is shown. In the lower panel the number of CMV-specific IFN-γ producing cells in relation to MSC infusions as measured in IFN-γ spots/100.000 peripheral blood-mononucleated cells (PBMC) is shown. Black arrows indicate MSC infusions.

Mentions: Trying to understand if, upon in vivo infusion, MSC could influence virus-specific T-cell-mediated immune responses, we evaluated by ELISPOT assays the frequency of virus-specific T cells circulating in the peripheral blood (PB) of 2 patients experiencing CMV reactivation soon after MSC infusion (UPN #9 and 14). Both patients showed an increase of CMV-specific IFN-γ producing cells in the PB along with CMV reactivation, despite the concomitant infusion of multiple MSC doses (Figure 1). In particular, in UPN #9 CMV-specific cells increased 18 times at day 44 after HSCT, upon CMV reactivation (16700 CMV DNA copies/mL of PB), compared to day 35 (preinfection levels). Virus-specific cells then started to decrease along with the resolution of CMV infection and raised again upon a second episode of CMV reactivation at day 86. Similarly, in UPN #14, CMV-specific T cells increased up to 4 times along with CMV reactivation at day 80 after HSCT.


Mesenchymal stromal cells do not increase the risk of viral reactivation nor the severity of viral events in recipients of allogeneic stem cell transplantation.

Lucchini G, Dander E, Pavan F, Di Ceglie I, Balduzzi A, Perseghin P, Gaipa G, Algarotti A, Introna M, Rambaldi A, Rovelli A, Biondi A, Biagi E, D'Amico G - Stem Cells Int (2012)

Frequency of CMV-specific T cells, secreting interferon gamma (IFN-γ) in response to a cocktail of CMV-specific peptides, as measured by ELISPOT assay in two patients reactivating CMV after having received mesenchymal stem cells (MSCs) for the treatment of steroid refractory graft versus host disease. Dotted lines on top of the panels indicate Ganciclovir administration. In the upper panel overall GvHD grading according to NIH criteria is shown. In the central panel Cytomegalovirus (CMV) reactivation trend as measured in copies/milliliter of peripheral blood (PB) is shown. In the lower panel the number of CMV-specific IFN-γ producing cells in relation to MSC infusions as measured in IFN-γ spots/100.000 peripheral blood-mononucleated cells (PBMC) is shown. Black arrows indicate MSC infusions.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369546&req=5

fig1: Frequency of CMV-specific T cells, secreting interferon gamma (IFN-γ) in response to a cocktail of CMV-specific peptides, as measured by ELISPOT assay in two patients reactivating CMV after having received mesenchymal stem cells (MSCs) for the treatment of steroid refractory graft versus host disease. Dotted lines on top of the panels indicate Ganciclovir administration. In the upper panel overall GvHD grading according to NIH criteria is shown. In the central panel Cytomegalovirus (CMV) reactivation trend as measured in copies/milliliter of peripheral blood (PB) is shown. In the lower panel the number of CMV-specific IFN-γ producing cells in relation to MSC infusions as measured in IFN-γ spots/100.000 peripheral blood-mononucleated cells (PBMC) is shown. Black arrows indicate MSC infusions.
Mentions: Trying to understand if, upon in vivo infusion, MSC could influence virus-specific T-cell-mediated immune responses, we evaluated by ELISPOT assays the frequency of virus-specific T cells circulating in the peripheral blood (PB) of 2 patients experiencing CMV reactivation soon after MSC infusion (UPN #9 and 14). Both patients showed an increase of CMV-specific IFN-γ producing cells in the PB along with CMV reactivation, despite the concomitant infusion of multiple MSC doses (Figure 1). In particular, in UPN #9 CMV-specific cells increased 18 times at day 44 after HSCT, upon CMV reactivation (16700 CMV DNA copies/mL of PB), compared to day 35 (preinfection levels). Virus-specific cells then started to decrease along with the resolution of CMV infection and raised again upon a second episode of CMV reactivation at day 86. Similarly, in UPN #14, CMV-specific T cells increased up to 4 times along with CMV reactivation at day 80 after HSCT.

Bottom Line: No patient presented severe form of infection.Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity.In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

View Article: PubMed Central - PubMed

Affiliation: Clinica Pediatrica, Università degli Studi di Milano Bicocca, Ospedale San Gerardo, 20900 Monza, Italy.

ABSTRACT
Mesenchymal stromal cells (MSC) are tested in clinical trials to treat graft versus host disease (GvHD) after stem cell transplantation (SCT). In vitro studies demonstrated MSC's broad immunosuppressive activity. As infections represent a major risk after SCT, it is important to understand the role of MSC in this context. We analyzed 24 patients (pts) receiving MSC for GvHD in our Unit between 2009 and 2011. We recorded viral reactivations as measured in whole blood with polymerase chain reaction for 100 days following MSC administration. In patients with a documented viral reactivation in the first 3 days following MSCs infusion the frequency of virus-specific IFNgamma-producing cells was determined through enzyme-linked immunospot assay. In our cohort of patients viral reactivation after MSC infusion occurred in 45% of the cases, which did not significantly differ from the incidence in a historical cohort of patients affected by steroid resistant GvHD and treated with conventional immunosuppression. No patient presented severe form of infection. Two cases could be checked for immunological response to viral stimulus and demonstrated virus specific T-cytotoxic lymphocyte activity. In our experience MSC infusion did not prove to trigger more frequent or severer viral reactivations in the post transplantation setting.

No MeSH data available.


Related in: MedlinePlus