Mesenchymal Stem Cells Found Around Blood Vessels in the Liver

Mesenchymal stem cells (MSCs) are found throughout the body and it is possible that every organ in our body has a MSC population. MSCs have the ability to differentiate into three main tissues: bone, fat and cartilage. However, the efficiency of this differentiation differs from one MSC population to another. Also, some MSCs can form smooth muscle for blood vessels and there is even evidence that MSCs can form blood vessels under certain conditions (for example, see Wingate K, Bonani W, Tan Y, Bryant SJ, Tan W. Acta Biomater. 2012 8(4):1440-9. doi: 10.1016/j.actbio.2011.12.032).

One of the places MSCs are usually found is around blood vessels. MSCs like to hang out on the outside of blood vessels in some tissues, and for this reason, MSCs are sometimes called “perivascular” stem cells.

One organ that has a stem cell population is the liver, but there is disagreement as to where they reside. Now a new publication has established that cells that hang out near blood vessels in liver are the MSC population in liver.

Eva Schmelzer from the McGowan Institute for Regenerative Medicine at the University of Pittsburgh has published a fine paper in the journal Stem Cells and Development detailing, with the help of her trusty laboratory colleagues, the characterization of liver MSCs.

Briefly, Schmelzer and her colleagues obtained fetal and adult lover tissue from tissue suppliers and minced them up, digested them with the appropriate enzymes, pushed them through cell strainers and then destroyed all the contaminating red blood cells. The remaining cells were grown in a cell culture medium. The stem cells would outgrow all the other cells, which would make their isolation and purification easy.

To purify the cells, Schmelzer’s co-workers used a technique called “flow cytometry.” When they had purified the liver MSCs, they set about characterizing them.

The liver MSCs grew quite well in culture and also grew quickly. They also expressed lots of surface proteins normally found on MSCs, confirming that they are MSCs. When gene expression experiments examined what genes these MSCs expressed, they expressed some smooth muscle genes and a several other genes enriched in cells near blood vessels. When Schmelzer examined cross sections of liver to determine where these cells are located, she found them curled up next to blood vessels.

In culture, the liver MSCs did not make very good cartilage or fat. However, they did make very good smooth muscle and bone. The efficiency of MSC differentiation tends to depend on where they were isolated. The rule of thumb is that MSCs most easily differentiate into those tissues that are closest to their own tissue of origin. Therefore, we would expect bone marrow MSCs to make better bone and cartilage than fat-based MSCs, and we would expect fat-based MSCs to make better fat than bone or liver-based MSCs. The ability of liver MSCs to be so good and making bone might be a little surprising, but when we consider that bone marrow stem cells begin their lives in the liver before they migrate to the bone marrow, perhaps this finding makes more sense.

In short, the adult and fetal liver contain a MSC population that is found on the outside of the blood vessels and these cells have an excellent capacity to make bone and smooth muscle for blood vessels. Thus liver biopsies might provide do more than provide material for diagnostic purposes – they might secure cells for regenerative purposes.