Energy Metabolism Analysis of Three Different Mesenchymal Stem Cell Populations of Umbilical Cord Under Normal and Pathologic Conditions

Abstract

Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a pivotal source of therapeutically active cells for regenerative medicine due to their multipotent differentiation potential, immunomodulatory and anti-inflammatory proprieties, as well as logistical collection advantages without ethical concerns. However, it remains poorly understood whether MSCs from different compartments of the human umbilical cord are therapeutically superior than others. In this study, MSCs were isolated from Wharton's jelly (WJ-MSCs), perivascular region (PV-MSCs) and cord lining (CL-MSCs) of hUC. These cells expressed the mesenchymal markers (CD90, CD73), stemness marker (OCT4), endothelial cell adhesion molecular marker (CD146), and the monocyte/macrophage marker (CD14) found within the MSC population implicated as a key regulator of inflammatory responses to hypoxia, was displayed by WJ-, PV-, and CL-MSCs respectively. A direct consequence of oxygen and glucose deprivation during stroke and reperfusion is impaired mitochondrial function that contributes to cellular death. Emerging findings of mitochondria transfer provide the basis for the replenishment of healthy mitochondria as a strategy for the treatment of stroke. Cell Energy Phenotype and Mito Stress tests were performed the energy metabolic profile of the three MSC populations and their mitochondrial function in both ambient and OGD cell culture conditions. PV-MSCs showed the highest mitochondrial activity. CL-MSCs were the least affected by OGD/R condition, suggesting their robust survival in ischemic environment. In this study, MSC populations in UC possess comparable metabolic capacities and good survival under normal and hypoxic conditions suggesting their potential as transplantable cells for mitochondrial-based stem cell therapy in stroke and other ischemic diseases.

Stem Cells as Drug-like Biologics for Mitochondrial Repair in Stroke

“…The mitochondria in the perivascular region MSCs showed the greatest activity while the MSCs from the cord lining demonstrated the highest survival rate. These findings suggest that hUC-MSCs may be a good source for mitochondrial transplantation for ischemic stroke treatment [77]. Additionally, co-culturing human umbilical vein endothelial (HUME) cells with MSCs improves aerobic respiration and TNT formation in in vitro IR injury models [66].…”

Mitochondrial activity of human umbilical cord mesenchymal stem cells

“…MSCs were harvested from cord lining (CL-MSCs), perivascular region (PV-MSCs), and Wharton's jelly (WJ-MSCs) of the human umbilical cord. [ 15 ] Mesenchymal markers (CD90 and CD73) were expressed by all three cell populations. Stemness marker (OCT4), endothelial cell adhesion molecular marker (CD146), and monocyte-macrophage marker (CD14) were expressed by WJ-MSCs, PV-MSCs, and CL-MSCs, respectively.…”

“…Stemness marker (OCT4), endothelial cell adhesion molecular marker (CD146), and monocyte-macrophage marker (CD14) were expressed by WJ-MSCs, PV-MSCs, and CL-MSCs, respectively. [ 15 ] OGD, apparent during stroke and reperfusion, results in dysfunctional mitochondria and consequently cell death. Evidence indicates that restoring mitochondrial function through mitochondrial transfer may be effective in treating stroke.…”

“…Data indicated that CL-MSCs number decreased the least post-OGD/R exposure, and PV-MSCs exhibited the greatest mitochondrial activity. [ 15 ] All three hUC-MSCs populations presented similar metabolic activity and survival in normal and hypoxic environments [ Figure 1 ]. These beneficial characteristics bolster hUC-MSCs therapeutic potential in stroke and other ischemic diseases.…”

“…Data indicated that all three cell populations displayed quiescent phenotypes and therefore preserved glycolytic and mitochondrial metabolism at low levels. [ 15 ] When subject to stressful conditions, hUC-MSCs augmented glycolytic metabolism to offset reduced mitochondrial activity. When the rate of decrease in oxygen concentration (OCR) was measured, only a minimal decrease in OCR was observed across OGD/R groups when compared to MSCs in normal conditions.…”