Human embryonic stem cell-derived mesenchymal progenitors—Potential in regenerative medicine

Abstract

Tissue engineering and cell therapy require large-scale production of homogeneous populations of lineage-restricted progenitor cells that easily can be induced to differentiate into a specific tissue. We have developed straightforward protocols for the establishment of human embryonic stem (hES) cell-derived mesenchymal progenitor (hES-MP) cell lines. The reproducibility was proven by derivation of multiple hES-MP cell lines from 10 different hES cell lines. To illustrate clinical applicability, a xeno-free hES-MP cell line was also derived. None of the markers characteristic for undifferentiated hES cells were detected in the hES-MP cells. Instead, these cells were highly similar to mesenchymal stem cells with regard to morphology and expression of markers. The safety of hES-MP cells following transplantation was studied in severely combined immunodeficient (SCID) mice. The implanted hES-MP cells gave rise to homogeneous, well-differentiated tissues exclusively of mesenchymal origin and no teratoma formation was observed. These cells further have the potential to differentiate toward the osteogenic, adipogenic, and chondrogenic lineages in vitro. The possibility of easily and reproducibly generating highly expandable hES-MP cell lines from well-characterized hES cell lines with differentiation potential into several mesodermal tissues entails an enormous potential for the field of regenerative medicine.

Small Molecule Mesengenic Induction of Human Induced Pluripotent Stem Cells to Generate Mesenchymal Stem/Stromal Cells

“…4). We conclude that iPS-and ES-MSCs displayed a greater propensity to undergo osteogenic and chondrogenic differentiation than adipogenic differentiation, and in this respect, our results resemble findings reported in ESC-derived MSCs [13,19,33], fetal, and other gestational product-derived MSCs [2, 5, 34 -38].…”

“…Similarly, primary deciduoplacental MSCs [34], umbilical cord blood [38], Wharton's jelly [35,36], and fetal MSCs [37,56] have been reported to have less adipogenicity than adult bone marrow MSCs. Consistent with this, the ESC-derived MSC literature to date either reports cells displaying low adipogenesis [13,19,33] or avoids commenting on relative adipogenic capability [8 -10, 12, 14, 16]. There are few reports as yet of iPS-MSCs, although Zhang et al performed a semiquantitative analysis of adipogenic and osteogenic differentiation to claim that differentiation was similar in bone marrow MSCs, fetal MSCs, and ES-and iPS-derived MSCs [57].…”

Concise Review: Epidermal Grafting: The Case for Pluripotent Stem Cells

“…This issue may eventually be much better addressed by pluripotent stem cell derivatives. At this point, in addition to basal keratinocytes, protocols are available for differentiation into melanocytes (unpublished data and [33]) and fibroblasts [34], mesenchymal stem cells [35], and adipocytes [36] that can be introduced into the final cell therapy product to improve its overall quality.…”

Human Embryonic Stem Cells Derived Mesenchymal Stem/Stromal Cells and their Use in Regenerative Medicine

“…Also, our preliminary data showed hESCs derived MSCs (hESCs-MSCs) with fibroblast-like morphology ( Figure 1) expressed CD105 and FIBRONECTIN as MSC specific markers (unpublished data; Figure 1). Karlsson et al [12] used Xeno-free derivation of MSCs from hESCs as an optimal protocol for the first time and reported these cells with MSCs phenotype and differentiation potential into mesodermal tissues do not form teratomas when transplanted under the kidney capsule of severe combined immunodeficiency (SCID) mice [12]. Similar to these potential, reports demonstrated that hESCs-MSCs not only were phenotypically similar to bone marrow derived MSCs (BM-MSCs) and adipose derived MSCs (AMSCs), but also, showed higher in vitro proliferation capacity and equivalent differentiation potential into adipocytes and osteocytes [13].…”