Regenerative medicine
has tried to change the approach to treating heart disease. Molecular changes
in the fibroblasts in the laboratory have enabled scientists to convert these
cells into cardiomyocytes. The cells are first converted into pluripotent
cells, cells that can convert into other types of cells. These are referred to
induced pluripotent stem cells (iPSC). They are then converted into
cardiomyocytes. Methods have also been developed where fibroblasts can be
directly converted into cardiomyocytes without the conversion into pluripotent
stem cells.
‘Scientists have discovered the molecular changes that take place in the scar-forming fibroblast cells during their conversion into healthy heart muscle cells called cardiomyocytes.’
Scientists have now been
able to chalk out the details of this conversion.
They have been able to identify the step-by-step changes that occur
during this conversion including the molecular pathways and the important
regulators that control the conversion. This knowledge will help scientists
replicate the process in a live heart and make the treatment a reality.
The scientists used
single cell RNA sequencing technology along with mathematical modeling and
genetic and chemical approaches in their studies.
During their research, t
hey
found that during the direct conversion of non-cardiomyocytes into
cardiomyocytes, all the cells do not mature at the same times, and therefore
while some cells are fully reprogrammed, some are partially reprogrammed while
others may remain unconverted. The scientists hope to use this phenomenon
to optimize treatment outcomes in a patient with heart attack.
Working on mouse
fibroblast cells, the scientists found that:
- By changing the
cell cycle status of the fibroblasts, the outcomes of the new myocyte
formation could change.
- The
susceptibility of the fibroblasts to reprogramming varies. Those formed
more recently may be easier to be reprogrammed into cardiomyocytes.
- Changes were
noted in the machinery responsible for protein synthesis. Depletion of a
splicing factor called Ptbp1 involved in the process appeared to favor the
conversion of fibroblasts to cardiomyocytes.
- New surface
markers for the enrichment of the induced cardiomyocytes were also
discovered.
The researchers hope
that these discoveries will not only benefit research related to heart attack,
but also other conditions like nervous system-related disorders, diabetes and
cancer.
Heart Attack
During a heart attack,
the blood supply to a particular part of the heart stops due to a block in the
supplying artery. The muscle cells of the heart called cardiomyocytes in the
affected area die. Other cells called fibroblasts proliferate in these areas,
resulting in the formation of fibrous or scar tissue. The scar tissue does not
contribute to the pumping effect of the heart. Thus, following a large attack,
the pumping ability of the heart reduces, and the patient could suffer from
heart failure. Emergency treatment is primarily directed to minimize damage to
the heart muscle.
Reference:
- Ziqing Liu, Li Wang, Joshua D. Welch, Hong Ma, Yang Zhou, Haley Ruth Vaseghi, Shuo Yu, Joseph Blake Wall, Sahar Alimohamadi, Michael Zheng, Chaoying Yin, Weining Shen, Jan F. Prins, Jiandong Liu and Li Qian. Single-cell transcriptomics reconstructs fate conversion from fibroblast to cardiomyocyte. Nature (2017) doi:10.1038/nature24454
Source: Medindia
