The tissue specific nature of mesenchymal stem/stromal cells: gaining better understanding for improved clinical outcomes

Ofer Shoshani ,Dov Zipori ,Nir Shani

doi:10.14800/rd.780

Abstract

Mesenchymal stem/stromal cells (MSCs) are multipotent progenitors that are derived from most adult tissue as well as cord blood and placenta. MSCs are defined by their adherent nature, ability to propagate in culture and capacity to differentiate into bone fat and cartilage. However, many studies have shown that MSCs, derived from different tissues, differ both in their in situ and in vitro phenotypes. Despite abundance of MSCs studies, little is known about the molecular events that control their tissue specific nature. Two recent studies comparing MSCs derived from different tissues have now found clues to the molecular mechanisms that control the tissue specific nature ofthese cells. In the first, the superior genomic stability of adipose derived MSCs (ASCs), compared to bone marrow (BM) MSCs, was explained by reduced H19, a long non-coding RNA expression and increased p53 activity of ASCs. In the second, a compression of abdominal and subcutaneous ASCs reveals poor propagation, differentiation and migration capacities of abdominal ASCs that is explained by their increased tendency to over-accumulate reactive oxygen species (ROS) in culture. ROS over production in abdominal ASCs was shown to be controlled by the NADPH oxidase NOX1. The unique features of MSCs derived from different tissues suggest a tissue specific molecular signature arising from the tissue of origin that is retained during culture. The implications of this phenomenon on our understanding of the role and function of MSCs in situ as well as on their clinical utilization, is discussed.

Highlights

Mesenchymal cells from bone marrow (BM) and adipose tissues were isolated and propagated under tissue culture conditions since the 1960's [1,2,3]
In spite of the common properties of Mesenchymal stem/stromal cells (MSCs) that were listed in the International Society for Cellular Therapy (ISCT) guidelines, significant differences between mesenchymal stem/stromal cells that were derived from different tissues were observed since their identification
The perivascular niche was proposed as an origin for MSCs of various tissues [15], but it was recently shown that CD34 positive adipose derived MSCs (ASCs) (CD34+ cells were demonstrated to be responsible for the CFU-F capabilities of stromal fat cells) do not localize in proximity to blood vessels and are not of perivascular origin [16]

Summary

RESEARCH HIGHLIGHT

The tissue specific nature of mesenchymal stem/stromal cells: Gaining better understanding for improved clinical outcomes. In light of the above, our recent findings regarding the increased tendency of aASCs and not of scASCs to express NOX enzymes, accumulate reactive oxygen species, accumulate pro-inflammatory cytokines and undergo extensive apoptosis, may provide novel mechanistic clues to the involvement of ASCs progenitors in the development of the metabolic syndrome [19] This notion is further substantiated by the claim that MSCs are derived from a perivascular cells [15] and by the many evidences that connect ROS production by vascular cells to the development of obesity: NOX1 was shown to be expressed in vascular smooth muscle cells, and its mRNA expression was up-regulated and activated by vascular pathological stimuli [40, 41]. Further studies of the specific nature of abdominal ASCs may provide additional mechanistic indications to the genetic signature that promote ASCs phenotype and possibly ROS accumulation in obese individuals

Does the epigenetic state of MSCs dictate their tissue specific traits?

Findings

Conclusions