Proteomic Comparison of the Secreted Factors of Mesenchymal Stem Cells from Bone Marrow, Adipose Tissue and Dental Pulp

Abstract

Mesenchymal stem cells (MSCs) have therapeutic potential in various diseases, including myocardial infarction. Recently, the importance of the therapeutic effects of secreted factors from MSCs is increasing, but their identification has not progressed. In this study, we uncover the secreted protein profiles of MSCs derived from bone marrow, adipose tissue and dental pulp. Shotgun proteome analysis of conditioned MSC media by mass spectrometry identified 1533 proteins totally and 124 secreted proteins commonly produced among all three MSCs. The commonly secreted factors include already well-known factors whose functions are linked to MSCs' biological effects, such as CTGF, SERPINE1, TGFB1, DKK3 and MYDGF, and also include newly identified factors whose roles are not well investigated, for example AIMP1, CLEC11A, GAS6, HDGF, INHBA, and PCSK5. Computational biological pathway analysis revealed that these common factors strongly relate to tissue regeneration pathways such as angiogenesis, migration, and inflammatory response. Further analysis showed enrichment of ossification, sprouting, and organ survival factors, suggesting connection to the functions closely related to MSCs' therapeutic effects. This list of commonly secreted proteins could provide a reliable resource of biological factors which explain various effects of MSCs and would be useful for identifying new therapeutic factors produced from MSCs.

Dental Stem Cell-Derived Secretome/Conditioned Medium: The Future for Regenerative Therapeutic Applications

“…The secreted extracellular proteins were suggested to be responsible for the regenerative effects of MSCs including angiogenesis, migration, inflammatory response, ossification, and organ survival. A closer resemblance was notable between protein sets isolated from bone marrow MSC-CM and adipose MSC-CM rather than dental pulp MSC-CM [103]. Comparing MSCs from apical papilla-CM to bone marrow MSC-CM, proteins responsible for angiogenesis, immunomodulation, chemotaxis, neuroprotection, antiapoptosis, and extracellular matrix formation were detected in both CM.…”

Secreted factors from adipose tissue-derived mesenchymal stem cells suppress oxygen/glucose deprivation-induced cardiomyocyte cell death via furin/PCSK-like enzyme activity

“…Recently, we identified a numerous number of trophic factors secreted from three different types of MSCs, bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (ASCs), and dental pulp-derived mesenchymal stem cells (DPSCs), by conducting comprehensive proteomic analysis of CM from these cells [17] . In the study, we also identified 124 commonly secreted factors.…”

“…In the study, we also identified 124 commonly secreted factors. Because the CM of all the 3 MSCs has been known to show similar cardioprotective activities [13] , [17] , it could be expected that those MSCs protect cardiomyocytes in the same fashion with identical trophic factors. In this context, the list of commonly secreted factors could provide promising candidates to identify factors which explain the protective activity against MI commonly observed in MSCs.…”

Current Status and Future Prospects of Genome-Scale Metabolic Modeling to Optimize the Use of Mesenchymal Stem Cells in Regenerative Medicine

“…One potential use for GEMs would be to explore the different metabolic capacities of hMSCs from different sources. There have been some reports, albeit limited, explaining possible differences in the proliferative, differentiation, and immunomodulatory abilities of hMSCs isolated from various tissues (Liu et al, 2007;Hass et al, 2011;Secunda et al, 2015;Tachida et al, 2015). As hMSCs are isolated from disparate microenvironments, some with large differences in their surroundings, their optimal survival conditions and, possibly, utilization potential may differ.…”