Mesenchymal Stem Cells Engineered to Inhibit Complement-Mediated Damage

• Published in: Blood 2012-11, Vol.120 (21), p.1253-1253
• Main Authors: Soland, Melisa, Bego, Mariana, Colletti, Evan, Porada, Christopher D, Zanjani, Esmail, St. Jeor, Stephen, Almeida-Porada, Graca
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.V120.21.1253.1253

Abstract 1253 Mesenchymal stem cells (MSC) preferentially migrate to damaged tissues and, due to their immunomodulatory and trophic properties, contribute to tissue repair. Although MSC express low levels of molecules, such as CD59, which confer protection from complement-mediated lysis, MSC are recruited and activated by anaphylatoxins after transplantation, potentially causing MSC death and limiting therapeutic benefit. It has been demonstrated that transduction of MSC with a retrovirus encoding HCMV US proteins resulted in higher levels of MSC engraftment and diminished recognition by the immune system, due to a decrease in HLA-I expression. Here we investigate whether engineering MSC to express US2, US3, US6, or US11 HCMV proteins can alter complement recognition, and thereby protect MSC from complement attack and lysis. US HCMV proteins increased MSC CD59 expression to differing degrees, as determined by flow cytometric evaluation of the median fluorescence intensity ratio (MFI) (n=3). CD59 MFI on untransduced MSC was 128±33, and this value remained largely unchanged on MSC transduced with an empty retroviral vector (MSC-E) and on MSC transduced with US11 (MSC-11). In contrast, a significant increase in CD59 MFI was seen in MSC transduced with US2 (MSC-2), US3 (MSC-3), and US6 (MSC-6), with MFIs of 273±35 (p