Abstract
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.
Highlights
Mesenchymal stromal cells (MSCs) as bone marrow cells of nonhematopoietic origin are rated as somatic stem cells characterized by self-renewal and multipotent differentiation [1,2,3]
The most significant decrease of CFU-F number was revealed in patients with non-Hodgkin’s lymphoma (NHL) (17±5, p
The number of CFU-F in bone marrow of patients with MM, acute leukemia (AL) and AA was similar to or even higher than the appropriate donor value. These patients were found to be highly heterogeneous within the group, and the amount of MSC precursors in a significant proportion of patients (30% of cases for MM, 33% - in AA, 43% - in AL) was reduced and did not exceed the lower percentile values of donors
Summary
Mesenchymal stromal cells (MSCs) as bone marrow cells of nonhematopoietic origin are rated as somatic stem cells characterized by self-renewal and multipotent differentiation [1,2,3]. Disadvantages of allogeneic cells are related to the possibility of infection, the need for cryopreservation and material storage, and immunogenicity revealed by some authors. To this end, there are some data demonstrated allogeneic MSCs may fail to weaken, but rather worsen the disease [14,15]. There are some data demonstrated allogeneic MSCs may fail to weaken, but rather worsen the disease [14,15] Despite these cells are considered to be low immunogenic, MSCs when administered may cause socalled instant blood-mediated inflammatory reaction (BMIR) which significantly limits the survival, engrafting and efficiency of donor MSCs [16]
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