Comprehensive Literature Review: Renal Failure & Stem Cell Therapy

This literature review explores the application of stem cell therapy in treating renal failure, covering the mechanisms of action, challenges, and opportunities in implementation. The review synthesizes research from various studies, including those focusing on embryonic and mesenchymal stem cells, preclinical models, and clinical trials. The main themes discussed are stem cell technology for chronic and acute renal failure, treatment of kidney injury by stem/stromal cells, and the challenges and opportunities in implementing stem cell therapy. The review highlights the potential of stem cells in repairing damaged nephrons, improving kidney function, and offering new treatment options for this incurable disease, while also acknowledging the need for further research and addressing safety concerns. This research analyzes studies that focus on various aspects of renal failure and stem cell therapy and provides a comprehensive view of current and future strategies.

LITERATURE REVIEW ON
RENAL FAILURE

TABLE OF CONTENTS
INTRODUCTION...........................................................................................................................3
MAIN BODY...................................................................................................................................3
CONCLUSION................................................................................................................................8
REFERENCES................................................................................................................................1

INTRODUCTION
Literature review helps in broadening the current knowledge on the particular subject
matter. This helps in critically examining and reviewing the viewpoints of various authors in
relation with effectiveness of stem cell therapy in treating renal failure. Renal failure is occurred
when kidney loses the ability to filter the waste from the blood. Evidence-based outcomes and
incorporating contemporary research with physiology justified claims.
MAIN BODY
According to Chawla and et.al., 2014, renal failure occurs when kidney loses the ability
to filter the waste from the blood. The decreased ability of kidney to maintain electrolyte
homeostasis and fluid in the body is evident to chronic kidney disease. This results in decreased
ability to excrete excess potassium, acid and phosphate. Renal failure is caused due to several
health problems or disease. Diabetes is known to be one of the most common cause of kidney
failure. High blood pressure is referred to as the second most cause of ESRD. There are various
other diseases such as urinary tract problems, autoimmune disease, nephrotic syndrome, etc.
which in turn affect the functioning of the kidney. The common symptom to Kidney disease is,
nausea, vomiting, pruritus, nocturia, stomatitis, muscle twitches, cramps, decreased mental
acuity, fatigue, seizure, under-nutrition, peripheral neuropathies, etc. On the other hand,
symptoms associated with acute renal failure which mainly includes irregular heartbeat,
confusion, fatigue, nausea, fluid retention, chest pain, seizure and lower urine output. However,
Bianchi and et.al., 2014, stated that Renal function is effectively clinically monitored by
measurements of urinalysis, blood urea nitrogen and serum creatinine (Rani and et.al., 2015).
Renal failure is said to be advanced when GFR ≤15 mL/min/1.73 m2 and it in turn results in
concrete urine lost. This is effectively diagnosed by Urinalysis, quantitative urine protein, renal
biopsy and ultrasonography. Treatment associated with renal failure are controlling underlying
disorders, Vitamin D supplements, protein restriction, treatment of anaemia. Therapeutic
management of renal failure which is done by therapies like stem cell and renal replacement.
Theme 1: Stem cell technology for the treatment of chronic and acute renal failure.
Study of Pino and Humes, 2010, was focused on stem cell technology for the treatment of
chronic and acute renal failure. Stem cells helps kidney in repairing damaged nephrons and
restoring kidney function. The motive behind choosing this topic is increasing morbidity and
mortality because of chronic renal failure disorders. Scope of review is based on stem cells, renal

stem cell, embryonic stem cell, acute renal failure, end stage renal disease, cell-based therapy
and tissue engineering. The inclusion criteria of study were review of cell-based therapies to
analyse effectiveness of stem cell therapy as it is promising multifactorial treatment approach.
The pattern of review comprises evaluation of current stem cell technologies like adult stem cell,
induced pluripotent stem cell and embryonic stem cells.
In accordance with a review, it is identified that there is considerable motivation to
improve therapies with the motive of reducing mortality, morbidity and increasing impact on
economy because of acute renal failure (Kidney disease: how could stem cells help?, 2019). Stem
cell therapy is a hopeful approach which comprise native abilities of cell afforded by a billion
years of evolution. In the study, researcher focused on methodology of direct application of stem
cells (Matthay, Pati and Lee, 2017). In accordance with this first step outlined was mode of
action as per which main strength of therapy is introduction of supplementary cells in damaged
kidney of adult. This aid in repairing and regenerating cells and therefore this therapeutic
management for treating renal failure is known as natural healing process. Further, there is trans
differentiation approach of Mesenchymal Stem cells. In this approach obtain easily accessible
stem cells from another that is non diseased tissue. The cells in this process expand in vitro and
then reintroduce to integrate with target damaged tissue.
In accordance with the review, it is outlined that embryonic stem cells have potential for
renal regeneration given their pluripotency (Gupta and Lam, 2016). From the study it is outlined
that embryonic stem cells differentiate kidney structures when placed in embryonic kidney
microenvironment. Injection of ES cells expresses β-galactosidase in embryonic kidneys.
Further, when ES cells expresses β-galactosidase in presence of leukemia inhibitory factor which
suppress differentiation. Before injecting ES cells are infected with Green fluorescence protein.
This affects renal hemodynamic by raising Glomerular hyperfiltration. The main points of
discussion in review was in section of direct application of step cells which comprise mode of
action, tran differentiation of Mesenchymal cells, embryonic stem cells, induced pluripotent stem
cells and Metanephroi transplantation. The questions in review was focused on modes of action
and new development of stem cell therapy which are effective to renal failure. Thus, from the
study, it has been concluded that stem cell therapies are considered as effective clinical
treatment for renal failure because the modes of action of stem cells are based on stage of renal
injury of patient. The disagreement in study was on transformed cells which are easily generated

via stem therapy pose safety issue. The gap in review was limited links of therapies with
pathophysiology of topic (Li and et.al., 2015). Hence, it can be said that research helped in
gaining understanding over the importance of stem cell therapies for treating renal failure.
Theme 2: Treatment of Kidney injury by stem/stormal cells
Crigna and et.al., 2018, has presented his understanding on treatment of kidney injuries
with focus on preclinical models. The reason for writing review is that this article which is based
on treatment of kidney injury is of immense importance in order to gain idea behind ways of
treatment of renal failure. The review is of great importance as it will help in analysing the
treatment options for kidney injuries such as stem cell therapies, diabetic nephropathy, kidney
transplantation etc. The author has done a systematic research and analysis of various literature
which is concerned with the use of stromal cells and stem for different kidney diseases which is
focusing on preclinical models like cisplatin induced acute kidney disease, CKI, DN and KTx.
The literature at the end has summarised MSC mechanism, to monitor therapeutic effects,
applied search strategy and state of art on MSCs therapy for treatment of diseases which has
been mentioned.
The review of article which is on stem/ stromal cells for treatment of kidney injury with
focus on preclinical models. However the as per the article there is no best way to treat renal
failure no dosage, tissue source or mode of action has been there however the preclinical data
gives the beneficial effects of kidney disease. However from studying the article it can be seen
that MSC treatment has protective effect and it helps in reducing renal damage and also helps in
improving kidney function. stated that kidney is one of the target organs in human body of
various diseases some of the common disease includes anaemia, dyslipidemia, hypertension etc.,
it is compromised that it results in emergence of other pathophysiological conditions like
cardiovascular diseases. A long-term disease which is Chronic kidney injury arises due to
decrease of glomerular filtration rate and increase of albuminuria. Cellular therapy could
contribute potentially to create a better outcome of nephropathy.
All the studies which has been related to clinical trials and animal models which were
related with treatment with stem cells has been taken. Studies which was related with allogeneic
and xenogeneic stem cell therapy has also been used. By the electronic search 2677 studies was
found. All the studies were reviewed and after detail analysis 299 studies has been selected. The

various question which was raised in order to provide an overview of the clinical studies and
preclinical studies of kidney disease which has been performed in the stem cell therapy field.
A recent study Song, Y. and et.al., (2019), with EV (extracellular vesicles)
suggests that there is meditation in order to restore ATP supply by the mitochondria transfer to
damaged cells. While the other author, Nguyen, Lapidot and Ruf, (2018)found that MSC
(mesenchymal stromal cells) derived CM does not only result in increase of tabular cell survival
which is due to induced proliferation and migration of kidney epithelial cells but it is also limited
to renal injury. One of the most important question which is where do cells move after
transplantation has also been analysed in study. The other topic which has been analysed in study
is about optical tissue clearing. In the past bio imaging techniques has been used in order to
enhance imaging resolution to subcellular level and to use them for vivo studies. The action
involved in renoprotective activity of MSC has also been analysed. The article which has been
reviewed shows the various other therapy such as diabetic nephropathy, AKI induced by
chemotherapy for treatment of renal failure. In brief the whole article which is Stem/ Stromal
cells for treatment of kidney injuries with focus on preclinical model (2018), gives an overview
of different types of therapies which can be used for treatment of kidney.
It has been found from the article which is on Stem/ stromal cell for treatment of kidney
injuries, that MSC is one of the most investigated cell-based therapy. The literature review
highlights the information about MSC therapy in clinical trials and preclinical studies in diverse
diseases. However, there is not best administration route, tissue sources, specific mode of action
due to high difference between different kidney injuries. The animal model which has been
studied does not fully able to mimic the human disease therefore it is required that preclinical
data should be taken cautiously. Although MSC which has been used in clinical trials and are of
high safety and tolerability.
Theme 3: Challenges/ Opportunities in implementation of Stem Cell Therapy
Hickson, Eirin & Lerman (2017), outlined the challenges and opportunities for stem cell
therapy in patients with chronic kidney disease. The relevance of this article in the present report
lies in the fact that this will help in identifying the importance of stem cell therapy and its various
challenges and opportunities while implementing it on patients with renal failure. The review
would discuss novel interventions for the incurable disease and in order to encourage
regenerating capabilities two main cell types have been studied. Mainly, Clinical Trials and

Preclinical Studies related to EPC and MSC have been used in order to collect literature. In this
Literature review, after exploration of current practices related to stem cell therapy, its
effectiveness in curing renal failure is discussed and an overview or future strategies is presented
to conclude the review.
Renal failure, affecting 8-16% of world's population has always been a horror due to its
in-curability which ultimately leads to last stage of kidney failure and there are only
interventions that can be implemented since no proper treatment is available. In the present
review, researcher has included terms like stem-cell therapy, Mesenchymal Stem Cells,
Endothelial Progenitor Cells etc. and in order to collect data related to these terms, secondary
data is the major methodology that has been used i.e. clinical journals, In-vitro Studies, Mayo
Clinic Centre, Satellite Health Care Foundation etc. have been used to observe the treatment
given to patients suffering from renal diseases. In order to critique relevantly and substantially,
the author has used already researched literature review and references from 177 different
articles out of which some are systematic review related to EPC and MSC, stem cell based
therapy and strategies for improving these functions in future; and some are meta-analysis
covering barriers in the implementation mechanisms of EPC and MSC therapy.
In the review, mainly; in order to cure chronic kidney disease and formulate appropriate
interventions for renal failure; major cells i.e. EPCs and MSCs have been pointed out as most
beneficial cells for implementing stem cell therapy in order to treat renal failure as these cells do
not get damaged and proved to be most efficient cells in kidney disease therapy. This review also
briefly describes the concept of decrease in Urinary protein and urea, Glomerulosclerosis and
Interstitial Fibrosis and its association to renal failure. Author states that best stage for
implementation of Stem cell therapy is when Pathophysiological treatment i.e. Pathogenesis
reaches the stage of Nephrotoxic Inflammation as stem cell therapy acts as a assistant at this
stage in treating the problem. The major questions that have been addressed in this review is that
what are major challenges that implementation of Stem Cell Therapy in order to treat patients
suffering from renal failure. The review of article also discusses various opportunities that are
presented by this stem cell therapy.
The research paper agrees on the aspect that EPC and MSC are major cells that need to
be focused upon in order to boost up the regenerative potential that can help in minimizing the
pace at which deterioration takes place. However, there is need for more development and

advancement in present area but limited fund availability acts as the biggest restriction. Lastly,
those methods through which cell optimization can be improved also needs to be studies and
researched upon.
CONCLUSION
From the above study it has been concluded that, renal failure is occurred when kidney
loses the ability to filter the waste from the blood. The study was based on evidence-based
review which helped in outlining effectiveness of stem cell therapy for treating renal injury.
Stem cells helps kidney in repairing damaged nephrons and restoring kidney function. Hence,
from the study it has been summarized that stem cell therapy are effective for treating renal
failure because it aids in treating causes on the basis of different stages of development.

REFERENCES
Books and journals
Bianchi, F. and et.al., 2014. Potential advantages of acute kidney injury management by
mesenchymal stem cells. World journal of stem cells. 6(5). p.644.
Chawla, L.S. and et.al., 2014. Acute kidney injury and chronic kidney disease as interconnected
syndromes. New England Journal of Medicine. 371(1). pp.58-66.
Crigna, A.T. and et.al., 2018. Stem/stromal cells for treatment of kidney injuries with focus on
preclinical models. Frontiers in medicine. 5.
Hickson, L. J., Eirin, A., & Lerman, L. O. (2016). Challenges and opportunities for stem cell
therapy in patients with chronic kidney disease. Kidney international. 89(4). 767-778.
Pino, C.J. and Humes, H.D., 2010. Stem cell technology for the treatment of acute and chronic
renal failure. Translational Research. 156(3). pp.161-168.
Rani, S. and et.al., 2015. Mesenchymal stem cell-derived extracellular vesicles: toward cell-free
therapeutic applications. Molecular Therapy. 23(5). pp.812-823.
Song, Y. and et.al., 2019. Three-phase bi-directional wireless EV charging system with high
tolerance to pad misalignment. IET Power Electronics, 12(10). pp.2697-2705.
Nguyen, T.S., Lapidot, T. and Ruf, W., 2018. Extravascular coagulation in hematopoietic stem
and progenitor cell regulation. Blood, 132(2). pp.123-131.
Matthay, M.A., Pati, S. and Lee, J.W., 2017. Concise review: mesenchymal stem (stromal) cells:
biology and preclinical evidence for therapeutic potential for organ dysfunction following
trauma or sepsis. Stem Cells. 35(2). pp.316-324.
Gupta, N.R. and Lam, A.Q., 2016. Pluripotent Stem Cells for Kidney Diseases. In Recent
Advances in Stem Cells (pp. 69-84). Humana Press, Cham.
Li, Q and et.al., 2015. Transplantation of induced pluripotent stem cell-derived renal stem cells
improved acute kidney injury. Cell & bioscience. 5(1). p.45.
Online
Kidney disease: how could stem cells help?. 2019. [ONLINE]. Available
through:<https://www.eurostemcell.org/kidney-disease-how-could-stem-cells-help>
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