A new study by scientists from University
School of Medicine in St. Louis at Washington have found that a particular type
of stem cells are responsible for the calcification of the blood vessels in
chronic kidney patients, raising hope for better control and care.
‘Altering Gli1 cells to become healers instead of sealers could lower atherosclerosis risk.’
An associate professor of medicine and the director
of the Division of Nephrology Dr. Benjamin Humphreys who is also the senior
author of the study talks about the active process involved in the process "In
the past, this calcification process was viewed as passive -- just mineral
deposits that stick to the walls of vessels, like minerals sticking to the
walls of water pipes. More recently, we've learned that calcification is an
active process directed by cells. But there has been a lot of controversy over
which cells are responsible and where they come from."
Vascular Calcification in Chronic Kidney
There are two types of calcification of the
arteries that take place in chronic
kidney disease patients.
A) Atherosclerotic calcification:
- This is present in the intimal layer
- Leads to
- Deposition of
- Osteogenesis that
includes induction of osteoblasts
B) Medial Artery Calcification:
- This type of calcification is found to be common in chronic
kidney disease patients and people with diabetes.
- Occurs in
the vascular smooth muscle cells.
- It is also known as
Earlier it was believed that calcification of
the arteries was a passive process but current studies point towards an active
process. The passive process was believed to be due to an elevated serum
phosphate levels and an increase in the product of serum calcium phosphate.
This was thought to lead to an over saturation of the plasma.
Current studies are aimed at the association
between vascular calcification and osteogenesis. In calcified medial arterial
layers as well as in atherosclerotic plaques, there have been expression of key
regulators of bone structural proteins.
Gli1 Positive Stem Cells
Gli1 cells are adult stem cells that are
present in the outer layer of the arteries. These stem cells have the ability
to differentiate into a number of connective tissue like fat, bone and smooth
muscle. The study by Dr. Benjamin Humphreys and colleagues has found that these
stem cells are responsible for the mineral deposits that clog the arteries.
Mechanism of Clogging
Gli1 cells are stem cells that are directed
to generate smooth muscle cells in the arteries to enable healing and effective
contractive ability of the arteries. In chronic kidney disease, this mechanism
is disrupted with changes in signaling pattern resulting in these stem cells
being converted into osteoblasts, which are a type of bone cells that increase
the deposition of calcium in the arteries.
Dr Humphreys adds, "We expect to find
osteoblasts in bone, not blood vessels. In the mice with chronic kidney
disease, Gli1 cells end up resembling osteoblasts, secreting bone in the vessel
wall. During kidney failure, blood pressure is high and toxins build up in the
blood, promoting inflammation. These cells may be trying to perform their
healing role in responding to injury signals, but the toxic, inflammatory
environment somehow misguides them into the wrong cell type."
The researchers from The University School of
Medicine in St. Louis studied tissue samples of people who died from chronic
kidney disease to understand the effects on the aorta. The
scientists found that mineral deposits in the aorta of humans was found in the
same place as those found in mice, suggesting the mice studies would be
accurate in understanding the pathogenesis of this condition.
The researchers removed the adult stem cells
Gli1 in mice and observed the deposition of calcium in their aorta. It was
found that the there was no calcification of the aorta in mice.
Another study by researchers from Brigham and
Women's Hospital (BWH) ablated the Gli1 cells in mice with cardiac and kidney
fibrosis, without harming any other cell. It was found that the there was a
reduction in fibrosis with a rescue of the function of the heart.
Such studies point towards
- Gli1 being a possible target for drug therapy to lower
calcification and to restore the functions of the organs.
- Cautious prescription of oral calcium for people on
dialysis or with chronic kidney disease
- The Gli1 cells can
be induced to produce smooth muscle cells which will aid in healing the blood
However, Dr Humphrey cautions "Now that
we have identified Gli1 cells as responsible for depositing calcium in the
arteries, we can begin testing ways to block this process. A drug that works
against these cells could be a new therapeutic way to treat vascular
calcification, a major killer of patients with kidney disease. But we have to
be careful because we believe these cells also play a role in healing injured
smooth muscle in blood vessels, which we don't want to interfere with."
A considerable number of individuals with
chronic kidney disease die of atheroscleroses which can be avoided by effective
targeted treatment such as targeting the Gli1 cells. Stems cells have always
held an enviable position in medical studies and with the right kind of
stimulation, the Gli1 cells reverted as healers rather than sealers.
- Vascular Calcification: The Killer of Patients with
Chronic Kidney Disease - (http://jasn.asnjournals.org/content/20/7/1453.full)
calcification in chronic kidney disease - (http://www.ncbi.nlm.nih.gov/pubmed/16502129)
- Researchers have identified the cells responsible
for fibrosis, the buildup of scar tissue - (https://health-innovations.org/2014/12/02/researchers-have-identified-the-cells-responsible-for-fibrosis-the-buildup-of-scar-tissue/)