Human Embryonic Mesodermal Progenitors Highly Resemble Human Mesenchymal Stem Cells and Display High Potential for Tissue Engineering Applications

Abstract

Adult stem cells, such as human mesenchymal stem cells (hMSCs), show limited proliferative capacity and, after long-term culture, lose their differentiation capacity and are therefore not an optimal cell source for tissue engineering. Human embryonic stem cells (hESCs) constitute an important new resource in this field, but one major drawback is the risk of tumor formation in the recipients. One alternative is to use progenitor cells derived from hESCs that are more lineage restricted but do not form teratomas. We have recently derived a cell line from hESCs denoted hESC-derived mesodermal progenitors (hES-MPs), and here, using genome-wide microarray analysis, we report that the process of hES-MPs derivation results in a significantly altered expression of hESC characteristic genes to an expression level highly similar to that of hMSCs. However, hES-MPs displayed a significantly higher proliferative capacity and longer telomeres. The hES-MPs also displayed lower expression of HLA class II proteins before and after interferon-g treatment, indicating that these cells may somewhat be immunoprivileged and potentially used for HLA-incompatible transplantation. The hES-MPs are thus an appealing alternative to hMSCs in tissue engineering applications and stem-cell-based therapies for mesodermal tissues.

Engineering bone tissue substitutes from human induced pluripotent stem cells

“…Lack of teratoma formation of hESC-derived progenitors is presumably associated with down-regulation of genes involved in pluripotency, stemness, and cell proliferation, and increased expression of lineage-specific genes (30). Our microarray analysis revealed the occurrence of a proliferation/differentiation switch during bioreactor culture, providing the molecular evidence for strong lineage commitment and suppression of the teratoma-forming ability.…”

Osteogenic response of human mesenchymal stem cells to well-defined nanoscale topography in vitro

“…The isolation and enrichment of hMSCs were verified by flow cytometry, as described previously. 43 Three separate sets of experiments were performed for different biological evaluations: a 2-day culture for cell morphology evaluations (SEM, TEM, and fluorescence microscopy of phalloidin-stained cytoskeleton); a 2-week culture for cell proliferation, polymerase chain reaction (PCR) analysis of gene expression and alkaline phosphatase (ALP) activity evaluations; and a 4-week culture for TOF-SIMS analysis of cell-induced mineralization. In short, the samples were placed in cell culture wells (Falcon  CultureSlide 24-well, BD Biosciences, Franklin Lakes, NJ, USA) so that they completely covered the bottom area of the culture wells.…”

Bioreactor Systems for Human Bone Tissue Engineering

“…In addition, hMSCs are recognized to display strong immunomodulatory activity and paracrine regulatory effects [9,10], which could contribute to promote healing, neovascularization and graft integration following in vivo implantation. However, hMSCs display limited proliferation potential and inability to differentiate toward other lineages constituting the mature bone tissue, in addition to exhibiting strong decrease in functionality with protracted in vitro expansion and donor age [11][12][13][14], which might hinder their use for the effective reconstruction of skeletal defects in aged patients. As opposite, human embryonic stem cells (hESC) and human induced pluripotent stem cells (hiPSC) possess virtually unlimited expansion potential and ability to differentiate toward all specialized cell types constituting the human body [15][16][17] including cells of the vascular systems, with an increasing number of scientific reports lately demonstrating the potential of pluripotent stem cells and their mesenchymal derivatives for bone engineering in vitro and in vivo [18][19][20][21][22][23][24][25].…”