Human Bone Marrow Mesenchymal Stem/Stromal Cells Preserve Their Immunomodulatory and Chemotactic Properties When Expanded in a Human Plasma Derived Xeno-Free Medium

Abstract

Due to their immunomodulatory and chemotactic properties, hMSC are being explored to treat immune-related diseases. For their use in human therapies, it is necessary to culture hMSC in xeno-free conditions. In this study, the impact that a xeno-free medium based on a human plasma derivate has on these properties was analysed. Bone marrow-derived hMSC preserved their immunosuppressive and immunostimulatory properties, as observed with in vitro assays with hMSC cocultured with mixed leukocyte reactions or with mitogen-stimulated leukocytes. Moreover, hMSC expanded in xeno-free medium were recruited by macrophages in both migration and invasion assays, which indicates that the cells maintained their chemotactic properties. These data suggest that xeno-free expanded hMSC preserved their immunomodulatory and chemotactic properties, indicating that the described xeno-free medium composition is a potential candidate to culture and expand hMSC for human cell therapies.

The Potentials and Caveats of Mesenchymal Stromal Cell-Based Therapies in the Preterm Infant

“…Isolation and expansion techniques are still not standardized harboring the risk of variable quality of MSC cell preparations. Currently, MSC differentiation during expansion and related loss of function cannot be monitored by quality control assays, but expansion in cell culture using xeno-free media represents a promising research direction [ 147 ]. Furthermore, expansion of autologous MSCs should be taken into the conceptual consideration to overcome the risks and ethical concerns of allogenic transplantation.…”

Application Prospects of Mesenchymal Stem Cell Therapy for Bronchopulmonary Dysplasia and the Challenges Encountered

“…Still, allotransplantation risks are present, although phase I clinical trials do not show any short-term side effects [ 57 , 66 , 67 ]. Presently, the differentiation of MSCs and the loss of related functions cannot be monitored by quality control experiments [ 68 ]. Most recently, GMP-grade MSCs derived from hiPSCs have been used in refractory graft-versus-host-disease (GVHD) in clinical trials [ 69 ].…”

“…MSC transplantation for BPD treatment requires ethical review and evaluation before clinical trials. The differentiation and related functional loss of MSCs during amplification cannot be monitored by quality control analysis, but cell culture without animal components is a promising research direction [ 68 ]. Moreover, conceptually, the expansion of MSCs should be considered to overcome the risks and ethical concerns of allotransplantation.…”

Stem Cells from Human Extracted Deciduous Teeth Expanded in Foetal Bovine and Human Sera Express Different Paracrine Factors After Exposure to Freshly Prepared Human Serum

“…Moreover, it has been suggested that these supplements are suitable for in vitro expansion of MSCs (Haque and Abu Kasim 2017;Bieback et al 2012;Blazquez-Prunera et al 2017b). Several recent studies suggested that the immunomodulatory properties of MSCs are dependent on the type of supplements such as FBS, pHS and commercially produced cell culture supplement that used for their expansion (Blazquez-Prunera et al 2017a;Komoda et al 2010). However, no major complications have been reported in clinical trials using MSCs expanded with different supplements (Yubo et al 2017;Yim et al 2016).…”