By Debosree Pal, Jawaharlal Nehru Centre for Advanced Scientific Research, India

During the development of an embryo, the initial mass of cells that possess the capacity to constantly divide and give rise to all mature cell types of an organism are referred to as the stem cells. Stem cells have a capacity known as pluripotency, derived from the Latin term plurimus meaning very many and potens that refers to their capacity to differentiate into all cell types. Two independent reports, one by Martin Evans and Mathew Kaufman and another by Gail R. Martin in 1981 established the in vitro culture of embryonic stem cells from mice. In 1995, James Thomson and his colleagues at the Wisconsin National Primate Research Center, University of Wisconsin-Madison reported the successful culture of non-human primate embryonic stem cells from rhesus monkeys. These ground-breaking discoveries laid the foundation for stem cell therapy.

The first ever stem cell therapy to be practiced clinically was in 1956 in the form of bone marrow transplantation. Bone marrow has multipotent stem cells that give rise to all type of cells of the blood and hence can be effectively used as a treatment for leukaemia. Along similar lines, limbal stem cell therapy for replacing wounded or lost corneal tissue has been a success too.

A multitude of diseases such as Parkinson’s disease, Alzheimer’s disease, or Duchenne muscular dystrophy do not have a permanent cure. In this scenario, stem cell therapy to replace and replenish degenerated neural cells or muscle cells may be the only possibility of a potential cure. But major efforts are still needed in this area. Recently, efforts are also being focused on the re-programming of adult cells into naïve stem-cell like cells called induced pluripotent stem cells (iPSCs), which can be further differentiated into the required cell type. The advantage of iPSCs is since they are derived from the cells of the patient who needs them, the problem of foreign tissue rejection by the body is ruled out.

Long non-coding RNAs as emerging players of stem cell dynamics

As we know, DNA is coded into RNA which is translated into proteins, the molecular players of all physiological processes. However, as has been proved by the ENCODE and FANTOM projects, approximately 2% of the DNA is transcribed protein-coding RNA, whereas 90% of the remaining RNA molecules are not. The question arises, what is the function of these ‘non-coding’ transcripts? More than a decade of research has revealed that non-coding (nc)RNAs participate in various housekeeping and regulatory functions in the body. The subset of these ncRNAs that are more than 200 nucleotides in length are called long non-coding (lnc)RNAs. In the context of stem cells, these lncRNAs have been shown to coordinate and fine-tune their pluripotency, cell fate specification, tissue morphogenesis and cellular differentiation. In such a scenario, it has become crucial to study the roles of lncRNAs in stem cell dynamics to achieve a step further towards making stem cell therapy a routine procedure.

 LncRNAs as potential candidates for regenerative medicine for arthritis?

According to studies by the CDC, between 2013 and 2015, 22.7% of the adults in the US had been diagnosed with some form of arthritis, osteoarthritis being the most common. By 2040, 26% of adults (aged above 18 years) are predicted to be diagnosed with arthritis and joint inflammation. A more chronic form of arthritis, rheumatoid arthritis, affects as much as 1% of the worldwide population and puts 3.6% of women along with 1.7% of men at risk of developing rheumatoid arthritis. In India, an incredible 15% of the population is affected by arthritis. Like other diseases such as cancer, diabetes and AIDS, arthritis does not have any permanent cure and contributes to disability, limitation of capacity to work and activity and also increased risk of fall injuries.

 

A recent study published in the journal Bioscience Reports by Zhang et al. focused on the role of a particular lncRNA, named DANCR (Differentiation Antagonizing Non-Protein Coding RNA) in the process of chondrogenic differentiation. Mesenchymal stem cells derived from the synovial membrane and synovial fluid of joints (SMSCs) have been shown to possess a high potential to differentiate into cells of the chondrogenic lineage specifically which in turn can be used for engineering of cartilage tissue.

Patients suffering from rheumatoid arthritis or osteoarthritis could resort to such regenerative medicine for the reversal of joint damage in the future.

Zhang et al showed that DANCR lncRNA promotes the proliferation of SMSCs and contributes to their ability to differentiate into the chondrogenic lineage. They have additionally delved into the mechanistic aspects of this phenomena.

Future directions

Stem cell therapy promises to be an attractive option to replace lost tissue with a new one, one that is sustainable and derived from one’s own body. Although regenerative medicine is being successfully used to treat arthritis, there is always room for improving current treatments. Can lncRNAs such as DANCR thus be considered as key players whereby the survival and differentiation capacities of synovial stem cells can be better regulated? Can lncRNAs become the future of improving stem cell therapy for arthritis and other similar diseases?

Reference:        

Zhang L, Sun X, Chen S, Yang C, Shi B, Zhou L and Zhao J (2017) Long noncoding RNA DANCR regulates miR-1305-Smad 4 axis to promote chondrogenic differentiation of human synovium-derived mesenchymal stem cells. Bioscience Reports 37

About Me:

I am a 5^th year PhD student at the Molecular Biology and Genetics Unit, JNCASR, India. Designing problems and troubleshooting them to understand biological phenomena is what attracts me to the world of molecular biology. I also like travelling and reading in my spare time.