Possibility of Aggravation of Tissue Sclerosis after Injection of Multipotent Mesenchymal Stromal Cells Near the Forming Cicatrix in the Experiment

Abstract

The peculiarities of tissue sclerosis after injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and stained with Vybrant CM-Dil cell membrane dye were studied by light microscopy with luminescence. The surgical intervention consisting in ligation of the great vein was followed by tissue sclerotic transformation caused by direct damage and chronic inflammation caused by the presence of slowly resorbed ligature. Injection of stromal cells after this intervention led to formation of more extensive scar. This can attest to the possibility of stromal cells differentiation into connective tissue cells, fibroblasts, and stimulation of proliferation and collagen synthesis by host fibroblasts. A decrease in the volume of dense fibrous connective tissue due to scar reorganization at latter terms cannot not excluded.

Some Special Aspects of Liver Repair after Resection and Administration of Multipotent Stromal Cells in Experiment

“…According to our published data [21,22] and the results of other researchers [19,20,23,24], most of the MSCs injected into tissues remain viable for a very short time. A sharp change in the microenvironment of cell existence, the transition from comfortable conditions of in vitro cultivation to completely different conditions of in vivo functioning contribute to the death of a significant portion of the injected MSCs.…”

“…There are also results indicating the incorporation of MMSCs into the vessel walls of granulations developing at the site of tissues damaged during surgery [22]. Differentiation of MSCs into cells of connective tissue is possible [21,30].…”

“…MMSCs were obtained from the bone marrow of a male Wag inbred line rat weighing 180 g and aged 6 months, and then were characterized and cultured as described in our previous works [21,22,25,26]. Isolated MMSCs express some characteristic MSC markers (CD73, CD90, and CD105) and do not express the hematopoietic markers (CD14, CD20, CD45, and CD34).…”

“…Additionally, MMSCs were stained with red-fluorescent lipophilic membrane dye the Vybrant ® CM-Dil (Thermo Fisher Scientific, Waltham, Massachusetts, USA), which binds to the membranes of living suspension or adherent cells. Transfection and staining of MMSC membranes were carried out in accordance with our previous works [21,22,25,26].…”

“…Along with this, there is evidence in the literature that after injection into tissues, the MSCs die very quickly due to a sharp change in the microenvironment [19][20][21][22][23][24]. In addition, all works devoted to the effect of MSCs and their exosomes on the liver and reporting a good therapeutic efficacy of cell therapy do not contain any data on the possible complications and side effects of MSCs.…”