The Origins and Differences Between Human Mesenchymal Stem Cells

It was a scientific achievement story that began approximately 40 years ago and was previously met with skepticism. However, despite the criticism, many clinical trials and publications now center their focus on multipotent cells. Today, new studies suggest that not all MSCs are equal, and in this article, we explore this theory in greater depth.

It can take time until an innovative concept takes hold. Inventors with thoughts and ideas ahead of their time rarely receive credit during their lifetimes (Afanasyev et al., 2009). This was the situation for the godfathers of experimental hematology—Alexander Friedenstein (1924-1998) and Alexander Maximow (1874-1928). They set the experimental basis for the transplantation of hematopoietic stem cells and the cellular therapies that ensued. The primary research of Maximow provided the required scientific knowledge for Friedenstein, who had the potential to develop these concepts. At present, Friedenstein is attributed with the discovery of mesenchymal stem cells (MSCs) (Afanasyev et al., 2009).

The work of both Friedenstein and Maximow was met with considerable skepticism. However, thousands of publications dealing with MSCs can now be found in the PubMed database from the US National Library of Medicine at the National Institutes of Health. Around 6,000 publications were added in 2016 alone.

Different Types of Mesenchymal Stem Cells

I’ve been working with MSCs for more than ten years. In that time, the technologies for this field of biological research have advanced. The cells have been used extensively, but regarding fundamental knowledge of MSC physiology, we’ve seen a few new insights.

Dr. Hagen Wieland, the Development Department, PromoCell

Ten years in MSC research: Dr Hagen Wieland has seen significant changes in his field of research. Today he works in the Research and Development Department at PromoCell.

Ten years in MSC research:

Dr. Hagen Wieland has seen significant changes in his field of study. Today he works in the Research and Development Department at PromoCell.

MSCs are considered adult stem cells, and at present, they are thought to emerge from perivascular cells found in the walls of blood vessels (Crisan et al., 2008; Oh and Nör, 2015).

We can find MSCs in virtually every tissue type—closely linked to the number of blood vessels. Their task is tissue homeostasis, and therefore, their presence is vital for the body to function.” Wieland said.

Human mesenchymal stem cells are supposed to be multipotent, as they can differentiate into cells of mesodermal lineages (like myocytes, adipocytes, osteocytes, and, chondrocytes) and also of endodermal lineages (hepatocytes, insulin-producing β-cells) and ectodermal (neurons) (Ullah et al., 2015). Distinct stem cell populations may perform in varying ways and show a changing potential to differentiate. Whether those differences are the result of cell culture, donor variation, or intrinsic properties is still unclear.

When we isolate MSCs from different origins, we find differences. Cells from adipose tissue can be CD34-positive, a contradiction to the criteria of the International Society for Cellular Therapy.

Dr. Hagen Wieland, the Development Department, PromoCell.

The latest studies have demonstrated that the expression of that marker relies on culture conditions, cell origin, and passage number (Lin et al., 2012).

Wieland also said that “I don’t believe that there is only one type of MSCs. I think we are facing different subgroups. But MSCs from the bone marrow are the prototype.”

Scientific Success Depends on Culture Conditions and Cellular Identity

Culture conditions and cellular identity are why both the growth medium and the separation technique play an important role in achieving a distinct MSC population.

Standardization is still an issue in MSC research, even today, roughly 40 years after their discovery. Many labs are still using DMEM with FCS, but the quality of the serum fluctuates from batch to batch. You can avoid those issues if you use defined and serum-free media. There have been many advances in technology, and you can buy defined MSCs and state-of-the-art media with consistent quality. Many scientists are discouraged by the pricing, but when you take the hours of troubleshooting, testing, and the time needed for reproducing deviating experiments into account, it might be an investment that could give you more robust results.

Dr. Hagen Wieland, the Development Department, PromoCell.

Multipotency of mesenchymal stem cells: These adult stem cells can be derived from various tissues and organs. They show the ability to differentiate into a number of cell types, such as myocytes, neurons, and osteoblasts.

Multipotency of mesenchymal stem cells: These adult stem cells can be derived from various tissues and organs. They show the ability to differentiate into several cell types, such as myocytes, neurons, and osteoblasts.Defining criteria of mesenchymal stem cell: The International Society for Cellular Therapy (ISCT) has established particular markers and properties that distinguish MSCs from other cell types.

Defining criteria of a mesenchymal stem cell: The International Society for Cellular Therapy (ISCT) has established particular markers and properties that distinguish MSCs from other cell types.

Experimental results across several laboratories can only be compared if they use a comprehensive protocol of MSC origin, reagents, and techniques, and also with successive cell characterization. In the scientific society, awareness of the need for standardizing mesenchymal stem cell research is increasing, specifically as various journals request authentication of MSCs before they agree to publish the papers.

MSCs: Applications in Biomedicine

Alexander Hackel is a Ph.D. student at Germany’s Essen University Hospital and has a vast array of knowledge around the heterogeneity of MSCs, which is a major challenge in this field of research.

In his research, Hackel is studying the impacts of different types of MSCs on T cell immune function and natural killer cells (Petri et al., 2017). “We are assessing the effects of MSCs in the context of autoimmune and inflammatory diseases such as graft-versus-host disease,” he explained.

Fighting graft-versus-host disease: PhD student Alexander Hackel from Germany’s Essen University Hospital investigates the therapeutic potential of different MSC types. Picture kindly provided by Alexander Hackel.

Fighting graft-versus-host disease:

Ph.D. student Alexander Hackel from Germany’s Essen University Hospital investigates the therapeutic potential of different MSC types. Picture kindly provided by Alexander Hackel.

Soon, the immune regulatory properties of mesenchymal stem cells will be used by doctors to prevent graft-versus-host disease, in the case of cortisol resistance. “One of the next steps is to test our hypotheses in an animal model,” he added. “If everything works out as planned, our findings could translate into clinical use within three to five years – it´s very exciting work.

Scientists will be capable of introducing more specific clinical uses once they completely understand the mechanisms controlling MSC functions. Using MSCs, hundreds of clinical trials were performed for cell therapy in 2013 (Wei et al., 2013). As with the graft-versus-host disease, they can also be used for treating immune diseases such as multiple sclerosis, amyotrophic lateral sclerosis (ALS), stroke, and Crohn’s disease. Tissue repair is another major application. MSCs can be used for treating myocardial infarction and can also assist in the regeneration of periodontal tissue defects. Co-transplantation of both HSCs and MSCs can even be used for treating radiation victims.

Applications are so broad that MSCs could also help to treat a multitude of lifestyle diseases. Such cells could even help to treat Alzheimer’s disease and stroke patients.

Dr. Hagen Wieland, the Development Department, PromoCell.

Diseases of the musculoskeletal system particularly respond to mesenchymal stem cell therapies. Doctors could potentially use adult stem cells to treat patients suffering from slipped disks, osteoporosis, or joint problems.

As MSC research continues to gain traction, standards should be established to create similar research results. This would not only speed up the development of research but would also expedite successive clinical translation. Wieland is confident: “I think the time of MSCs has just begun.”

About PromoCell

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Last updated: Apr 25, 2019 at 7:53 AM

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