Molecular and Functional Phenotypes of Human Bone Marrow-Derived Mesenchymal Stromal Cells Depend on Harvesting Techniques

Abstract

Mesenchymal stromal cells (MSC) harvested in different tissues from the same donor exhibit different phenotypes. Each phenotype is not only characterized by a certain pattern of cell surface markers, but also different cellular functionalities. Only recently were different harvesting and processing techniques found to contribute to this phenomenon as well. This study was therefore set up to investigate proteomic and functional properties of human bone marrow-derived MSCs (hBM-MSC). These were taken from the same tissue and donor site but harvested either as aspirate or bone chip cultures. Both MSC populations were profiled for MSC markers defined by the International Society for Cellular Therapy (ISCT), MSC markers currently under discussion and markers of particular interest. While classic ISCT MSC markers did not show any significant difference between aspirate and outgrowth hBM-MSCs, our additional characterization panel revealed distinct patterns of differentially expressed markers. Furthermore, hBM-MSCs from aspirate cultures demonstrated a significantly higher osteogenic differentiation potential than outgrowth MSCs, which could be confirmed using a transcriptional approach. Our comparison of MSC phenotypes obtained by different harvesting techniques suggests the need of future standardized harvesting, processing and phenotyping procedures in order to gain better comparability in the MSC field.

Therapeutic Properties of Mesenchymal Stromal/Stem Cells: The Need of Cell Priming for Cell-Free Therapies in Regenerative Medicine

“…MSCs are found in several tissues, including bone marrow (BM) [ 15 ], adipose tissue (AT) [ 16 ], umbilical cord (UC) [ 17 ], dental pulp [ 18 ] and placenta [ 19 ], where these cells are surrounded by different cell types such as immune cells, epithelial cells, endothelial cells and stromal cells, and can exhibit immunomodulatory [ 20 , 21 ], angiogenic [ 22 , 23 ] and anti-oxidative properties [ 24 ]. Over the past decade the therapeutic action of MSCs has been investigated in several clinical trials for the treatment of many disorders including cardiovascular, neurodegenerative, immune, lung, liver, kidney and orthopedics diseases ( ).…”

Conditioned Medium from Human Amnion-Derived Mesenchymal Stromal/Stem Cells Attenuating the Effects of Cold Ischemia-Reperfusion Injury in an In Vitro Model Using Human Alveolar Epithelial Cells

“…MSCs are found in several tissues, including bone marrow (BM) [ 22 ], adipose tissue [ 23 ], umbilical cord (UC) [ 24 ], and placenta [ 25 ], where these cells exhibit both immunomodulatory and angiogenic [ 26 , 27 , 28 ] as well as antioxidative properties [ 29 ]. In recent years, due to both the ethical issues regarding the source of MSCs and the fact that the sampling of some MSCs is very invasive, increasing evidence supports the use of neonatal tissues, such as UC tissue and placenta tissue (e.g., amniotic membrane), as interesting sources of MSCs [ 28 , 30 , 31 ].…”

Extracellular Vesicles in Musculoskeletal Pathologies and Regeneration

“…It is well-established that MSC populations from different tissue sources are not identical but exert tissue-specific characteristics and functions (Sacchetti et al, 2016 ). Next to differences between MSCs from different tissues and anatomical localizations, isolation procedures and in vitro culture itself may also change the phenotype of MSCs (Bara et al, 2014 ; Herrmann et al, 2016 , 2019 ; Haddouti et al, 2020 ; Walter et al, 2020 ). Similarly, donor characteristics such as age and sex, as well as co-morbidities have been suggested to result in differences in MSC populations (Muschler et al, 2001 ; Dexheimer et al, 2011 ; Cassidy et al, 2020 ).…”