Regenexx Blog
5-13-19
Dr. Chris Centeno

Because our cells are smaller than we can see with the naked eye, ideas like cell stiffness seem foreign to us. However, it turns out that if a stem cell is stiff or squishy plays a major role in how it functions in the body. This morning we’ll dive into some new research that shows what happens when blood-forming stem cells go soft.

What Are Hematopoietic Stem Cells?
Hematopoietic stem cells (HSCs) are the stem cells in our bone marrow that make blood cells (e.g., red blood cells, white blood cells, platelets), via a process known as hematopoiesis. As blood cells wear out and die, HSCs pump new ones out of the bone marrow (and spleen) and into circulation. In other words, HSCs keep our circulating blood cells constantly restocked at the rate of hundreds of billions of new blood cells produced each day.

Our bone marrow makes up the core of our long bones, and as I’ve mentioned before, bones aren’t just the framework for the body, they are cell-producing factories. In addition to hematopoietic stem cells the bone marrow there are also mesenchymal stem cells (MSCs), which form into specialized cells of the musculoskeletal system, such as muscle cells, bone cells, and cartilage cells. However, today we’ll focus on HSCs.

The Results of Damaged HSCs
HSCs are more sensitive than their hardy MSC neighbors and can become irreversibly damaged. How? We can inherit mutations through our genes (i.e., genetic mutations) passed down from Mom, Dad, or earlier relatives. Environmental factors (e.g., smoking, pesticide exposure, etc.) can also create mutations (i.e., somatic mutations) in these cells. The blood cells produced by these mutated HSCs can be affected, which can lead to cancer and other diseases. Normally, our immune cells are on the job and destroy these mutated cells before they can become cancerous, but risks of somatic mutation increase with age or as the health of the immune system declines, and as a result when the mutation occurs in our hematopoietic stem cells, this is a marker for the chance of diseases such as hematologic cancers, stroke, and heart disease.

Making HSCs More Pliable May Result in Higher Blood Cell Yields in Cancer Treatment
HSCs aren’t typically extracted from the bone marrow for harvesting for cancer treatment, but to get higher numbers are instead induced using a drug out of the bone marrow and into the blood, which increases blood cell production count. But this technique doesn’t work for every patient, and the purpose of the new study was to investigate how to mobilize more HSCs into the bloodstream and therefore increase blood cell production.

Believing that in order to stay in place in the bone marrow where hematopoiesis takes place, HSCs must stay stiff, the researchers found a way to soften these stem cells, or make them more “deformable.” They did this by getting rid of a gene which produces a stiff cytoskeleton (Ptpn21). This allowed the HSCs to become more squishy and as a result, they were able to squeeze through bone marrow pores and to mobilize out of the bone marrow and into the blood. Stiffness could be returned to the HSCs in the mice by then increasing the protein Septin1, allowing the HSCs to remain in their bone marrow niches. Researchers believe this finding could lead to more effective ways to treat blood diseases, such as cancer, in the future.

The upshot? It’s hard to imagine that a little thing like how stiff or squishy cells are can make such a big difference. In this case, this new technology may add another way to treat cancer patients by finding subtle ways to get more healthy stem cells from the bone marrow and into the rest of the body.