Stem Cell Research

Developing embryos in their blastocyst phase have so called embryonic stem cells, which are pluripotent in character. This means that they can differentiate into any cell type present in our body.

Besides differentiated cells, which form our tissues and organs, our body has undifferentiated cells, which have an ability to differentiate into specialized cell types. These cells are called adult stem cells or mesenchymal stem cells. These cells are multipotent, which menas that although they can give rise to other differentiated cell types, their ability to differentiate is limited compared with pluripotent stem cells.

Stem cells have raised a lot of interest as a source for replacement of various diseased cells, tissues and organs of our body, particularly after the invention of the method to generate so-called induced pluripotent stem cells from differentiated skin cells by cellular reprogramming was published in 2007 (1,2). Professor Shinya Yamanaka was awarded Nobel Prize in Physiology or Medicine already in 2012.

Despite the importance of this innovation, further research has been, and will still be needed, before wide use of clinical applications with differentiated pluripotent stem cells can be achieved, due to the potential difficulties in controlling the differentiation process of the implanted (differentiated) pluripotent stem cells.

Therefore, the adult stem cells have been considered safer source for regenerative medicine purposes. Homing of mesenchymal stem cells (MSCs) to the injured body sites is important.  Characterization  of  the  MSCs  has shown that they express  a  receptor  called  CD44  in  their  plasma membrane, which binds to extracellular carbohydrate hyaluronan.

This has relevance to the homing of the MSCs, since injured locations tend to accumulate a large amount of hyaluronan (3). We have also revealed that human bone marrow MSCs have an extensive CD44-dependent hyaluronan coat (4), and even secrete hyaluronan-coated extracellular vesicles (5).

Expansion of the MSCs may attenuate their ability to differentiate properly into specific lineages. Thus, optimization of expansion culture conditions may be beneficial in order to maintain the good properties of the stem cells. In our studies using titanium-coated surfaces (6,7) we observed that titanium oxide coating may improve the proliferation capacity of the MSCs without adverse effects on the differentiation capacity.

For pluripotent stem cells to fulfill the prospects they have been given, the differentiation protocols to generate the desired cell types must be strictly developed. We have taken efforts to find optimize the culture conditions to differentiate pluripotent stem cells into chondrocytes, and even compared the chondrogenic potential between HS306 embryonic stem cell line and our own induced pluripotent stem cell line (8). Later, the differentiation protocol was further simplified (9).

Related articles

  1. Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S: Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131: 861-872, 2007 [Pubmed] [Full text]

  2. Yu J, Vodyanik MA, Smuga-Otto K, Antosiewicz-Bourget J, Frane JL, Tian S, Nie J, Jonsdottir GA, Ruotti V, Stewart R, Slukvin II, Thomson JA: Induced pluripotent stem cell lines derived from human somatic cell. Science 318: 1917-1920, 2007 [Pubmed] [Full text]

  3. Lammi PE, Lammi MJ, Tammi RH, Helminen HJ, Espanha MM: Strong hyaluronan expression in the full-thickness rat articular cartilage repair tissue. Histochem Cell Biol 115: 301-308, 2001 [Pubmed] [Full text]

  4. Qu C, Rilla K, Tammi R, Tammi M, Kröger H, Lammi MJ: Extensive CD44-dependent hyaluronan coats on human bone marrow-derived mesenchymal stem cells produced by hyaluronan synthases HAS1, HAS2 and HAS3. Int J Biochem Cell Biol 48: 45-54, 2014 [Pubmed] [Full text]

  5. Arasu UT, Kärnä R, Härkönen K, Oikari S, Koistinen A, Kröger H, Qu C, Lammi MJ, Rilla K: Human mesenchymal stem cells secrete hyaluronan-coated extracellular vesicles. Matrix Biol 64: 54-68, 2017 [Pubmed] [Full text]

  6. Kaitainen S, Mähönen AJ, Lappalainen R, Kröger H, Lammi MJ, Qu C: TiO2 coating promotes human mesenchymal stem cell proliferation without the loss of their capacity for chondrogenic differentiation. Biofabrication 5: 025009, 2013[Pubmed] [Full text]

  7. Qu C, Kaitainen S, Kröger H, Lappalainen, Lammi MJ: Behavior of human bone marrow-derived mesenchymal stem cells on various titanium-based coatings. Materials 9: 827, 2016 [Pubmed] [Full text]

  8. Qu C, Puttonen KA, Lindeberg H, Ruponen M, Hovatta O, Koistinaho J, Lammi MJ: Chondrogenic differentiation of human pluripotent stem cells in chondrocyte co-culture. Int J Biochem Cell Biol 45: 1802-1820, 2013 [Pubmed] [Full text]

  9. Qu C, Lammi MJ: Induction of chondrocyte-specific gene expressions in human embryonic stem cells differentiated under feeder-free culture conditions. Curr Regen Med 7: 54-63, 2017 [Full text]

Last updated April 27, 2020