Download Mesenchymal Stem Cell Based Therapeutic Intervention

JSCG
Journal of Stem Cells and Genetics
Opinion Article
Open Access
Mesenchymal stem cell based therapeutic intervention
against viral hepatitis: A perspective
Vikas Saxena
University of Maryland, Baltimore, USA
*Corresponding Author:
Vikas Saxena DVM, Ph.D.
Center for Vascular and Inflammatory Diseases, School of Medicine, University of Maryland, Baltimore, MD 21201, USA
Tel: +1-614-607-4216
Email: [email protected]
Received on: February 27, 2017 | Accepted on: February 27, 2017 | Published on: March 13, 2017
Citation: Vikas Saxena. Mesenchymal stem cell based therapeutic intervention against viral hepatitis: A perspective. J Stem Cells and Genetics 2017; 1(1): 1-2.
doi: 10.00000/jscg.2017.104
Copyright: © 2017 Vikas Saxena. This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC-BY)
(http://creativecommons.org/licenses/by/4.0/) which permits commercial use, including reproduction, adaptation, and distribution of the article provided the
original author and source are credited.
Published by Scientific Synergy Publishers
Abstract
Viral hepatitis is the seventh leading cause of mortality around the world resulting in 1.5 million deaths annually. Acute viral
hepatitis is mostly self-limiting in nature, but chronic infection leads to liver failure and hepatocellular carcinoma. In those cases,
liver transplantation is indicated. Limited supplies of donor livers require development of alternative approaches. Use of
mesenchymal stem cells as a source of hepatocyte in cases of viral hepatitis is discussed.
Keywords: Viral Hepatitis; Hepatitis A; Hepatitis B; Hepatitis C; Hepatitis D; Hepatitis E; Liver Transplantation; Mesenchymal
Stem Cells.
Abbreviation: HAV: Hepatitis A Virus; HBV: Hepatitis B Virus; HCV: Hepatitis C Virus; HDV: Hepatitis Delta Virus; HEV: Hepatitis
E Virus; DAA: Direct Acting Antiviral.
Opinion
The liver is an important organ of the body. Being nutrient
rich, it is also a target for several infectious diseases. Infectious
viral hepatitis, which is inflammation of liver due to viral
infection, is the seventh leading cause of mortality around the
world [1]. There are five major classes of viruses inducing
hepatitis: hepatitis A virus [HAV], hepatitis B virus [HBV],
hepatitis C virus [HCV], hepatitis Delta virus [HDV] and hepatitis
E virus [HEV]. HAV, an RNA virus, is transmitted mainly through
fecal-oral route by ingestion of contaminated food. HBV, a DNA
virus, is transmitted through exposure to contaminated blood,
semen and other body fluids. HBV can also be transmitted from
mother to child at the time of birth. HCV, an RNA virus, and like
HBV, can be transmitted through exposure to infective blood
and blood products. HDV is a satellite RNA virus to HBV, i.e.
HDV infections occur only in those who are already infected
with HBV. Dual infection of HBV and HDV results in more
serious disease and worse outcome. HEV, an RNA virus, is
mostly transmitted through consumption of contaminated food
and water.
J Stem Cells and Genetics 2017
All these infectious hepatotropic viruses induce hepatitis
that pose a greater challenge to health worldwide. HAV and
HEV are endemic viruses in several low incomes, third-world
countries. Viral hepatitis is generally acute and self-limiting in
nature. However, it can turn in to a chronic form of infection,
mostly in Immunocomprised individuals or under immune
suppressed conditions e.g. in a solid organ transplant recipient
undergoing immunosuppressive drug treatment, which may
lead to fulminant hepatitis and liver failure. Viral hepatitis
induced by HBV and HCV more commonly progress towards
liver cirrhosis which leads to fibrosis and poses an increased
risk of hepatocellular carcinoma or liver cancer. HAV, HBV, and
HEV are controllable due to availability of vaccines; however, in
2011 vaccine against HEV was licensed in China only, and is not
widely available. There is no vaccine available against HCV;
however, recent developments of direct acting antiviral [DAA]
drugs led to an important breakthrough. These new drugs can
cure viral infections in most patients.
Despite availability of vaccine and drugs, there has been a
steady increase in the number of deaths worldwide attributable
to viral hepatitis. According to an estimate, between 1990-2013
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there was an increase of 63% deaths due to viral hepatitis of
which 96% were due to HBV and HCV. There were 1.5 million
deaths due to viral hepatitis in year 2013 alone [1].
Liver transplantation is recommended treatment for endstage liver diseases. However, in the cases of viral hepatitis, viral
recurrence after liver transplantation is a universal phenomenon.
It is more so because the use of immunosuppressive drugs
required during solid organ transplantation, which renders
host more vulnerable to spread of viral infection. Use of
antivirals before and after liver transplantation has been
recommended, but these antivirals have several side effects.
Also, it is complicated, with availability of an appropriate liver
donor as well as transplant rejection. Therefore, safe, cost
effective, and practical alternatives to liver transplantation,
especially in cases of viral hepatitis, are under investigation.
Mesenchymal stem cell [MSC] based therapeutic
intervention holds promise to overcome several challenges in
hepatic transplantation. MSCs are adherent, fibroblast-like cells
with the ability of self-renewal and to differentiate into multiple
mesenchymal cell lineages such as osteoblasts, chondrocytes,
adipocytes, and importantly, hepatocytes [2]. MSCs can be
derived from a variety of tissues, such as umbilical cord bone
marrow, trabecular bone, synovial membrane, and fetal tissues
such as lung, pancreas, spleen and liver, etc. [3-6]. By culturing
MSCs in chemically-defined media, they can differentiate into
hepatocyte-like cells possessing liver-specific genes and
functions [3, 7]. In animal models of liver injury, hepatic
engraftment of transplanted MSCs highlight clinical potential of
MSCs in the treatment of liver diseases in general and viral
hepatitis in particular [8, 9]. Since identification of MSCs as a
source for hepatocyte, a standardized procedure in compliance
with current Good Manufacturing Practices has been formulated
to ensure the safety, quality, and identity of cell products [6].
MSC derived hepatocyte as source of hepatocyte transplantation
are in clinical practice. Peng et. al. [10] had used HBV patientderived autologous marrow MSCs and transplanted them
through proper hepatic artery. It leads to a short-term
improvement in patients’ liver health. However, improvements
are needed in the long term.
Recently Wang et al. [11] made attempts to obtain MSCs
from liver. It was found that liver-derived human MSCs
[LHMSCs] are partially committed towards development into
hepatocytes and produce pro-angiogenic, anti-inflammatory,
and anti-apoptotic cytokines. LHMSCs were found to contain
MSC-like properties in form of morphology, immune functions
and differentiation. By growing LHMSCs in defined media
authors were able to generate hepatocytes; however, their
clinical significance needs to be assessed. Studies of this kind
give hope for the development of an effective hepatocyte pool
to be used in cases of terminal liver failure.
Transplantation of stem cell derived hepatocytes poses its
own challenges. There are chances that injected cells may
proliferate in other organs. By injecting cells directly into the
liver or through hepatic artery and also by modifying MSCs via
expression of liver-specific homing receptors, this challenge
can be overcome. Hepatocytes derived from MSCs need to have
a standard evaluation to assess their potential as fully functional
primary hepatocytes. Such evaluation parameters need to be
developed and standardized. Another important question is to
J Stem Cells and Genetics 2017
know how many cells to inject in a particular disease. The
evaluation criterion should include recommendation on
number of cells to be injected in a particular disease based on
the damage sustained by the liver. Finally, in cases of viral
hepatitis, there are chances that virus may infect newly
transplanted hepatocytes. Therefore, a treatment regimen
comprising pre- and post-transplantation viral suppression or
clearance will be required. By analyzing all above aspects in
empirical manner, hepatocyte transplantation in cases of liver
failure could soon become an effective therapeutic regimen.
Thus overall, viral hepatitis is a big burden on public health
being the leading cause of deaths worldwide. Despite availability
of vaccines and drugs to treat and control specific pathogens,
alternative methods of treatment, especially at the end-stage of
viral hepatitis progression provides an important opportunity
to improve public health. Liver transplant is one of the options
and among them mesenchymal stem cell derived hepatocytes
gives new hope to the patients.
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Mesenchymal stem cells in viral hepatitis Vikas Saxena 8 mesenchymal
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