Abstract

Impaired Functions of Bone Marrow Mesenchymal Stromal Cells in Patients with Hematological Malignancies are Partially Improved by Fibroblast Growth Factor

Ekaterina Y SheveZla, Marina A Tikhonova, Egor V Batorov, Vera V Sergeevicheva, Irina V Kryuchkova, Vladimir A Kozlov, Alexandr A Ostanin and Elena R Chernykh

Mesenchymal stromal cells (MSCs) possess a multi-lineage potential and immunoregulatory activities which provides them a great potential in cell-oriented technologies. However, their biologic properties may be impaired in various pathologies, so approaches to improving the ability of MSCs to expand and express the expected immunoregulatory properties represent one of the challenges for this novel therapy. In the present study, we characterized bone marrow-derived MSC expansion along with their functional properties in patients with hematological malignancies, and designed a strategy of ex vivo pretreatment with the basic fibroblast growth factor (FGFb) to improve MSC activities. Our results demonstrated those patients MSCs are generally consistent with the Minimal criteria proposed by International Society for Cellular Therapy to design MSCs, and, moreover, possess a well-defined ability to maintain hematopoiesis. At the same time MSC growth, immunosuppressive and osteogenic potential are significantly diminished in patients. Nevertheless, MSC generation in FGFb-enriched conditions was accompanied by a decrease of cultivation until confluence, increase in the cell yield and the number of cycling MSCs. In addition, similar to intact MSCs, FGF-treated MSCs exhibited a significant secretory activity but lowered immunosuppressive and osteogenic potential. These data indicate FGFb ability to correct impaired MSC expansion and note FGFb using is feasible to optimize MSC-based protocols in the treatment of some hematological malignancies.