Engineered Mesenchymal Cells Improve Passive Immune Protection Against Lethal Venezuelan Equine Encephalitis Virus Exposure

Abstract

Direct injection of monoclonal antibodies (mAbs) is an important strategy to immediately protect the recipient from a pathogen. This strategy is critical during natural outbreaks or after the intentional release of bio-weapons. Vaccines require weeks to become effective, which is not practical for first responders immediately deployed to an infected region. However, mAb recipients often require booster shots to maintain protection, which is expensive and impractical once the first responders have been deployed. The present study has shown, for the first time, that mesenchymal stromal cells are effective gene delivery vehicles that can significantly improve mAb-mediated immune protection in a single, intramuscular dose of engineered cells. Such a cell-based delivery system can provide extended life-saving protection in the event of exposure to biological threats using a more practical, single-dose regimen.

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

“…However, numerous studies have consistently demonstrated that IV-infused cells largely become trapped in the capillaries of the lungs, where they fail to survive longer than a few days [15,29,[31][32][33][34][35].This phenomenon reduces the potential therapeutic bene t of the administered MSCs, a limitation cited in both clinical trials and animal studies [27,36,37]. In contrast, studies recently reported that engineered MSCs administered by IM were still detectable at the implant site >100 days after transplantation, and they continued to secrete a functional antibody into circulation [38]. Thus, in the present study, three routes of HUC-MSC transplantation in db/db mice were compared.…”

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

“…This phenomenon reduces the potential therapeutic benefit of the administered MSCs, a limitation cited in both clinical trials and animal studies [33,42,43]. In contrast, studies recently reported that engineered MSCs administered by IM were still detectable at the implant site > 100 days after transplantation, and they continued to secrete a functional antibody into circulation [44]. Thus, in the present study, three routes of HUC-MSC transplantation in db/db mice were compared.…”

Human umbilical cord-derived mesenchymal stem cells ameliorate insulin resistance via PTEN-mediated crosstalk between the PI3K/Akt and Erk/MAPKs signaling pathways in the skeletal muscles of db/db mice

“…This phenomenon prompted us that MSC transfusion by IV limited the potential therapeutic benefit in both clinical trials and animal studies [ 27 , 36 , 37 ]. However, engineered MSC transplantation by IM can live last for more than 100 days, and they perform their function by secreting a functional antibody into circulation [ 38 ]. Thus, in the present study, three routes of HUC-MSC transplantation in db/db mice were compared.…”