Multipotent Stem Cells

Exploring what these stem cells are and what they can do

With their potential to self-renew and regenerate into tissues and organs, stem cells are promising candidates for regenerative medicine to treat many health conditions. But all stem cells are not created equal, and not all of them can differentiate and develop into any type of cells. Stem cells can be broadly categorized into three types, depending upon their differentiation potential to become specialized cells:

Totipotent stem cells: The word totipotent means having unlimited capacity. These types of stem cells have the potential to give rise to any and all human cells, and in theory can even give rise to an entire functional organism. They can differentiate into cells from all three germ layers.

Pluripotent stem cells: These cells have the ability to differentiate into all cell types in the body, but not the whole organism. Pluripotent stem cells are only present for a very short period of time in the embryo, then they differentiate into more specialized multipotent stem cells.

Multipotent stem cells: These cells develop into multiple specialized cell types present in a specific tissue or organ. They can give rise to all cell types of a particular germ layer, but not all three germ layers, unlike pluripotent cells. Most adult stem cells are multipotent stem cells. The primary function of an adult stem cell is the mantainence and repair of the tissue in which they are found. These cells usually remain quiescent without dividing or differentiating. They maintain the stem cell pool and await signals for activation. Multipotent cells are best exemplified by mesenchymal stem cells or the MSCs. MSCs can be derived from bone marrow stroma, heart tissue, adipose tissue, skin, gingiva and many other tissues.

Unipotent stem cells: These cells differentiate into a single type of cell and are found in adult organisms.

Clinical relevance:

Of all these stem cell type categories, multipotent stem cells are most relevant from clinical perspective. For decades, the best known source of multipotent stem cells has been the bone marrow, but more recently, placenta and umbilical cord have also been discovered as new sources of multipotent stem cells with greater plasticity[1]. Multipotent cells such as MSCs can be isolated by negative enrichment, and further by expression of certain cell surface markers such as Sca1 and c-Kit by flow cytometry.

Multipotent cells can be induced to undergo differentiation into a particular cell type within one germinal layer. For stem cell therapy, multipotent cells from bone marrow have been used in the treatment of blood cancers such a lymphoma and leukemia, owing to the ability of these particular cells to differentiate into blood cells, including lymphocytes and erythrocytes. MSCs derived from bone marrow have also been used for bone and cartilage therapy, as well as in cardiac ailments.

Pros and cons of multipotent stem cell use:

The biggest advantage of multipotent stem cells from a therapeutic perspective is that they are derived from one’s self and thus do not pose a threat by triggering an adverse immunological reaction. Another advantage of using multipotent stem cells is that they don’t come with ethical or religious issues, since these cells are isolated from adult organisms. The disadvantage of these cells, in addition to their limited proliferative potential, is their low yield. Since a large number of cells are needed for replacement therapies, multipotent stem cells are quite challenging to work with.

Challenges in stem cell research

The use of multipotent stem cells to regenerate tissues is a very exciting and remarkable achievement in biomedical science. However, we must acquire a more comprehensive knowledge to fully understand the potential of these cells for their safe delivery into human recipients. There are several challenges with stem cells that must be addressed.

One of the greatest challenges in stem cell therapy is their similarity with cancer cells. Stem cells and cancer cells share a common property of unlimited division. The difference is that the former is tightly regulated while the latter is uncontrolled. It is important to understand the requirements of stem cells to achieve the desired outcomes for these cells to be used in therapy, and to avoid their transformation into cancer cells. More research is needed to better understand the safety of stem cells, both pluripotent and multipotent, for their use in therapy.

In addition to safety, other needs must be met for a successful stem cell therapy. Cells must[2]:

Be able to differentiate into the desired cell types,
Survive in the recipient after transplant,
Integrate into the surrounding tissue after transplant and
Stay functional for the duration of the recipient’s life.

Research is also needed to develop efficient techniques for achieving higher yields of the right types of differentiated cells.

[1] G. Kögler, S. Sensken, J. A. Airey, T. Trapp, M. Müschen, N. Feldhahn, S. Liedtke, R. V Sorg, J. Fischer, C. Rosenbaum, S. Greschat, A. Knipper, J. Bender, O. Degistirici, J. Gao, A. I. Caplan, E. J. Colletti, G. Almeida-Porada, H. W. Müller, E. Zanjani, and P. Wernet, “A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential.,” J. Exp. Med., vol. 200, no. 2, pp. 123–35, Jul. 2004.

[2] “What are the potential uses of human stem cells and the obstacles that must be overcome before these potential uses will be realized? [Stem Cell Information].” [Online]. Available: http://stemcells.nih.gov/info/basics/pages/basics6.aspx. [Accessed: 04-Apr-2016].