Safety and immunological responses to human mesenchymal stem cell therapy in difficult-to-treat HIV-1-infected patients

Abstract

Objective HAART largely decreases morbidity and mortality in chronic HIV-1-infected patients, but immune nonresponders (INRs) with full viral suppression still fail to reverse the immune deficiency. This study evaluated the safety and immunological responses of human umbilical cord mesenchymal stem cell (MSC) therapy in HIV-1-infected INRs. Design and Methods A total of 13 HIV-1-infected INRs were enrolled in this pilot prospectively open-labeled controlled clinical trial. Seven patients were administered three umbilical cord-MSC transfusions at 1-month interval during 12-months of follow-up, whereas six control patients were treated with saline in parallel. Immunological parameters were monitored in these patients throughout the trial. Results All patients tolerated the umbilical cord-MSC transfusions well throughout the trial. The umbilical cord-MSC transfusions preferentially increased circulating naive and central memory CD4 T-cell counts and restored HIV-1-specific IFN-γ and IL-2 production in the INRs. These enhancements in immune reconstitution were also associated with the reduction of systemic immune activation and inflammation in vivo. Conclusions umbilical cord-MSC transfusions are well tolerated and can efficiently improve host immune reconstitution in INRs, suggesting that such treatments may be used as a novel immunotherapeutic approach to reversing immune deficiency in HIV-1-infected INRs (ClinicalTrials.gov identifier: NCT01213186).

Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs

“…Our results agree with recent findings showing that persistent IFN-I signaling plays a detrimental role during chronic lymphocytic choriomeningitis virus infection and that blockade of IFN-I signaling by IFNAR antibody could reverse T cell exhaustion and enhance antiviral immune response (3,4). The IFNAR blocking antibody will thus facilitate novel therapeutic development aimed at those difficult-to-treat HIV-1-infected patients with sustained IFN-I signaling during cART (23,24,40). HIV-1 reservoirs are refractory to antiretroviral therapies (ART) and remain the major barrier to curing HIV-1 (34,35).…”

Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases

“…Their results showed that MSCs as an adjunct therapy are safe and can now be explored further for the treatment of patients with MDR or XDR tuberculosis in combination with standard drug regimens [188]. The data suggested that MSCs transplantation may be used as a novel immunotherapeutic approach to reversing immune deficiency in HIV-1-infected INRs [190] .…”

Mesenchymal stem cells and infectious diseases: Smarter than drugs

“…An interesting clinical study has shown that UC-MSCs increase their circulating naive and central memory CD4 T-cell numbers and restore HIV-specific IFN-␥ and IL-2 production. In these patients there is systemic immune reactivation [55].…”