Mesenchymal Stromal Cells Cultured in Serum from Heart Failure Patients Are More Resistant to Simulated Chronic and Acute Stress

Abstract

Despite regulatory issues surrounding the use of animal-derived cell culture supplements, most clinical cardiac cell therapy trials using mesenchymal stromal cells (MSCs) still rely on fetal bovine serum (FBS) for cell expansion before transplantation. We sought to investigate the effect of human serum from heart failure patients (HFS) on cord blood MSCs (CB-MSCs) during short-term culture under regular conditions and during simulated acute and chronic stress. Cell survival, proliferation, metabolic activity, and apoptosis were quantified, and gene expression profiles of selected apoptosis and cell cycle regulators were determined. Compared to FBS, HFS and serum from healthy donors (CS) showed similar effects by substantially increasing cell survival during chronic and acute stress and by increasing cell yields 5 days after acute stress. Shortly after the termination of acute stress, both HFS and CS resulted in a marked decrease in apoptotic cells. Transcriptome analysis suggested a decrease in TNF-mediated induction of caspases and decreased activation of mitochondrial apoptosis. Our data confirm that human serum from both healthy donors and heart failure patients results in increased cell yields and increased resistance to cellular stress signals. Therefore, we consider autologous serum a valid alternative to FBS in cell-based therapies addressing severe heart disease.

Optimization of human umbilical cord blood-derived mesenchymal stem cell isolation and culture methods in serum- and xeno-free conditions

“…Besides FBS, different xeno-free, protein-based coating agents or modified culture surfaces for MSC culture have also been developed and are currently commercially available [ 22 , 23 ]. These factors, along with other adhesion-supporting protein components, are assumed to contribute to enhancing cell adhesion and proliferation of MSCs in many research applications [ 24 , 25 ]. Nevertheless, using FBS as coating sulotion also has limitations in term of risky in transferring animal factors to human [ 26 ], and the variation effect on each MSC lines depend on different commercial products.…”

Enhanced Effect of IL-1β-Activated Adipose-Derived MSCs (ADMSCs) on Repair of Intestinal Ischemia-Reperfusion Injury via COX-2-PGE2 Signaling

“…Adipose-derived mesenchymal stem cells (ADMSCs) can be differentiated into multiple stromal lineages, including cardiac myocytes and bone and muscle cells [6]. ADMSCs represent a promising avenue for the treatment of a variety of inflammatory and autoimmune diseases, including cardiac failure, spinal cord injury, sepsis, and intestinal IR injury [7][8][9][10][11]. On the one hand, ADMSCs can be differentiated into bone cells for repairing bone fracture [12]; on the other hand, ADMSCs secrete a number of cytokines to enhance tissue regeneration, suppress inflammatory reactions, and alleviate the severity of sepsis and organ injury [7,13].…”