Differentiation Potential of Human Postnatal Mesenchymal Stem Cells, Mesoangioblasts, and Multipotent Adult Progenitor Cells Reflected in Their Transcriptome and Partially Influenced by the Culture Conditions

Abstract

Several adherent postnatal stem cells have been described with different phenotypic and functional properties. As many of these cells are being considered for clinical therapies, it is of great importance that the identity and potency of these products is validated. We compared the phenotype and functional characteristics of human mesenchymal stem cells (hMSCs), human mesoangioblasts (hMab), and human multipotent adult progenitor cells (hMAPCs) using uniform standardized methods. Human MAPCs could be expanded significantly longer in culture. Differences in cell surface marker expression were found among the three cell populations with CD140b being a distinctive marker among the three cell types. Differentiation capacity towards adipocytes, osteoblasts, chondrocytes, and smooth muscle cells in vitro, using established protocols, was similar among the three cell types. However, only hMab differentiated to skeletal myocytes, while only hMAPCs differentiated to endothelium in vitro and in vivo. A comparative transcriptome analysis confirmed that the three cell populations are distinct and revealed gene signatures that correlated with their specific functional properties. Furthermore, we assessed whether the phenotypic, functional, and transcriptome features were mediated by the culture conditions. Human MSCs and hMab cultured under MAPC conditions became capable of generating endothelial-like cells, whereas hMab lost some of their ability to generate myotubes. By contrast, hMAPCs cultured under MSC conditions lost their endothelial differentiation capacity, whereas this was retained when cultured under Mab conditions, however, myogenic capacity was not gained under Mab conditions. These studies demonstrate that hMSCs, hMab, and hMAPCs have different properties that are partially mediated by the culture conditions.

Multipotent adult progenitor cells improve the hematopoietic function in myelodysplasia

“…We also demonstrated that MAPC cells can provide stromal support for MDSderived hematopoietic cells. We know from previous microarray data that human MAPCs express hematopoiesis-supporting cytokines SCF, CXCL5, IL-8, IL-11, TGF-1β, VEGF, ANGPT1 and SPARC [11], but future studies will need to investigate the secretome of MAPC cells when co-cultured with MDS BM cells to determine the responsible factor(s) for hematopoietic improvement seen in MDS. A general secretome analysis of human MAPC cells revealed the presence of molecules that are involved in extracellular matrix regulation and angiogenesis as well as secretion of cytokines that influence cells from the innate and adaptive immune system in their recruitment and effector function [21].…”

“…Compared with MSCs, they have significantly greater proliferation potential and differentiation potential (e.g., functional endothelium in vitro as well as in vivo) [11]. Like MSCs, MAPC cells have potent immunomodulatory effects in T cells [12][13][14], are nonimmunogenic for T-cell proliferation and cytokine production and even suppress T-cell activation and proliferation induced by alloantigens and mitogens in vitro.…”

Soliciting Strategies for Developing Cell-Based Reference Materials to Advance Mesenchymal Stromal Cell Research and Clinical Translation

“…Maintaining a hypoxic environment during culture, supplementing with growth factors including basic fibroblast growth factor, epidermal growth factor, and platelet-derived growth factor, and maintaining cells at subconfluent levels are important parameters that are associated with these improvements [11,12]. These conditions are known to influence retention of telomerase activity and maintenance of signaling pathways that are associated with pluripotency in other environments [13].…”

Titanium-Enriched Hydroxyapatite–Gelatin Scaffolds with Osteogenically Differentiated Progenitor Cell Aggregates for Calvaria Bone Regeneration

“…16,17 MAPCs are also capable of forming the three germ lineages, including the mesoderm that gives rise to bone tissue when dexamethasone is supplemented. 18,19 Recent studies demonstrate that clinical grade human MAPCs (Multistem Ò ) offer clinical relevance for the treatment of autoimmune disorders and cardiac infarction (ClinicalTrials.gov NCT00677859, NCT00677222); however, no in vivo applicability studies for bone regeneration have been reported.…”