Ischemic kidney diseases are serious health issues that lead to irreversible loss of kidney function and are commonly associated with high rates of mortality and morbidity. Many of the conditions captured under the term ischemic kidney disease occur as a result of decreased glomerular filtration rate (GFR) caused by vasoconstriction or loss of autoregulation. Ischemic kidney disease, or ischemic renal disease, is a contributing factor anywhere between 6% – 27% of end-stage kidney disease and is most common among patients 50 years old or older.
The progression of these types of kidney diseases is often multifaceted and involves complex hormonal-immunological cellular interactions. Since ischemic kidney disease often involves damage that occurs to many different types of cells, the conditions have often been demonstrated to be resistant to conventional therapy.
Considering mesenchymal stem cells (MSCs) provide renal protection, their anti-inflammatory and immunomodulatory properties are of interest in an effort to better understand how they can be therapeutically used to treat and prevent acute kidney ischemia (AKI).
In this review, Zhu et al. examine recent progress in the use of MSC to prevent kidney diseases, with a specific focus on chronic ischemic kidney disease (CIKD).
When used to treat CIKD, MSCs have been found to achieve renal cellular repair in a number of different ways. Initially, and upon infusion, MSCs home to the injury site and release homing receptors, growth factors, and anti-inflammatory cytokines to the injury site. They also release similar microparticles that promote kidney repair through internalization in other cells, allowing for reduced intrarenal inflammation and the promotion of vascular regeneration.
Examining the results of clinical trials exploring the use of MSC to treat CIKD, and considering patients with diabetes mellitus often develop chronic kidney issues, including diabetic nephropathy (DN), the authors believe the beneficial application of the anti-inflammatory, antioxidant, and immunomodulating features of MSC could help in the treatment of DN.
While Zhu et al. highlights the potential of MSCs in the treatment of CIKD in this review, they also identify potential limitations, including the potential for MSCs to form teratoma or other tumors (to date, no direct evidence of kidney tumor formation has been reported) and exactly how long the effects of MSC on kidney protection will last. As a way to address both potential limitations, the authors recommend longer follow-up times to ensure all potential detrimental effects of MSC use in humans are known and accounted for.
The review concludes that while further studies are needed to discern the chief elements of their actions and to define the optimal type (tissue source, preconditioning), dose, and delivery route, MSCs demonstrate remarkable potential for future treatment of ischemic kidney disease.
End-stage kidney disease (ESKD) occurs when the kidneys cannot function at a level that supports the body’s needs. The kidneys serve a critical role in the body, removing waste and excess water.
Patients with chronic kidney disease may find the functionality of their kidneys declines slowly over ten to twenty years before reaching this stage. The most common causes of ESKD are diabetes and high blood pressure.
How Is ESKD Treated?
The two primary conventional treatments for ESKD are dialysis and kidney transplants. Patients who have retained only 10%–15% of their kidney function typically require dialysis.
Dialysis takes over the following functions of the kidneys as their performance declines:
Removing excess waste, water, and salt
Maintaining safe levels of vitamins and minerals
Controlling blood pressure
Helping produce red blood cells
Frequently, patients require dialysis while they wait for a kidney transplant.
What Can Peptide BPC-157 Do for the ESKD?
Clinical studies examining peptides’ effects on restoring organ function found significant benefits in treating ESKD with peptide BPC-157. Peptides are strings of amino acids that create proteins in the body. While the body naturally produces peptides, scientists can also form them in a lab to mimic those in the body.
In a 2019 clinical case, a patient whose kidney function had declined to the point that he required five dialysis treatments a week to stay alive underwent peptide therapy to repair the organ damage.
The treatment resulted in a dramatic improvement in his kidney function and overall health. Within two months, the patient’s dialysis needs declined from five weekly treatments to one, and the peptides remarkably restored his gait, strength, and balance.
The Significance of Peptide Treatments
The importance of the healing effects of peptide treatments can’t be understated. Patients with chronic kidney failure, heart failure, and other conditions currently have minimal options through conventional medicine.
As peptide treatments and other innovative medical approaches deliver positive results, it opens the door to further studies and potential therapy options for previously untreatable conditions.
Current estimates indicate that kidney disease currently affects over 37 million US adults and over 10% of the global population[1]. Characterized by gradual loss of function, kidney disease generally progresses over time and culminates in the inability to remove waste and excess fluid from the blood[2].
Often demonstrating little to no symptoms in its early stages, chronic kidney disease tends to demonstrate increasing and dangerous symptoms as the condition advances.
To date, treatment for chronic kidney disease has been centered around causal control as a way of slowing the progression of the condition. However, these therapeutic treatment efforts, including multidrug therapy, have demonstrated an inability to reverse the condition from progressing to end-stage renal disease (ESRD) and requiring additional therapy, dialysis, or kidney transplantation.
Considering the high cost and disruption to normal life function associated with dialysis and the severe shortage of viable kidney donors, neither dialysis nor transplant has proven to be ideal or often recommended treatment strategies. As a result, there has been renewed interest in new and more effective therapeutic options to alleviate, cure, or prevent kidney disease and to improve a patient’s survival and quality of life.
Evaluating the numerous and growing therapeutic applications associated with stem cells’ ability for self-renewal, proliferation, and differentiation, Liu et al.’s review explores the potential benefits offered toward improving renal function and supporting structural repair in those afflicted with kidney disease.
Despite the promising benefits of using stem cells to kidney repair and disease treatment demonstrated through prior preclinical study, the authors point out that certain ethical issues regarding the origin of stem cells, and specifically embryonic stem cells (ESCs) need to be addressed and overcome before clinical application of SCs.
Regardless of the stated drawbacks, Liu et. al concludes that the existing evidence demonstrates that stem cell therapy appears to be a clinically viable alternative for kidney disease, specifically for restoring normal kidney function and for progressing understanding about tissue regeneration, drug screening, and disease modeling.
Although stem cells demonstrate promise in this regard and while the immunomodulatory properties of mesenchymal stem cells (MSCs) appear to make them the most promising SC for treating kidney disease, the authors also point out that further research is needed before definitively concluding which source of SC is best suited for this application.
As a result of this review, and in an effort to realize these findings into clinical applications in the future, the authors call for larger rigorously designed clinical trials to further assist in determining the clinical efficacy of SC therapy in kidney disease – including the appropriate selection of cell types, number of SCs required, and the appropriate route of administration.
Stem cells have been used to repair and regenerate tissue and have been shown in recent years to have the plasticity necessary to improve conditions of solid organs. Given the success of bone marrow stem hematopoietic stem cells in this type of regenerative medicine, scientists have speculated that bone marrow stem cell mobilizers may be beneficial for treating organs that have undergone injury. Let’s discover stem cells for acute kidney injury and what potential they have for this condition.
Bone marrow stem cell mobilizers are substances that act to encourage stem cells from the bone marrow to move into the blood, where they can be collected, stored, and later used to replace bone marrow via a stem cell transplant. A recent paper published in Current Protein and Peptide Science covers about a decade of research on two bone marrow stem cell mobilizers, granulocyte colony-stimulating factor (G-CSF) and Plerixafor (AMD3100).
G-CSF is a
glycoprotein that stimulates both stem cells and granulocytes to be released by
bone marrow and enter the bloodstream. It is produced by a variety of tissues
and immune cells and functionally acts as both a cytokine and a hormone.
Plerixafor also stimulates the immune system and is used in patients with
multiple myeloma and non-Hodgkin lymphoma.
According to the authors, the preclinical studies on the impact of these stem cell mobilizers confirm that these mobilizers may be an effective way to therapeutically approach with stem cells for acute kidney injury. While more research is needed to determine exactly how these bone marrow stem cell mobilizers act in acute kidney injury and what role they may play in therapy, these initial data appear to justify more investigations into the value of these substances for kidney care.
Reference: Xu, Y. et al. (2017). Stem cell mobilizers: Novel
therapeutics for acute kidney injury. Current
Protein Peptide Science, 18(12), 1195-1199.
Kidney diseases are among the most expensive and most debilitating diseases. Total costs are in excess of $50 billion a year, with $30 billion spent on people with end-stage renal disease including hemodialysis and kidney transplantation. People with kidney diseases have diminished quality of life, and substantial amounts of their time are devoted to medical treatment. Not surprisingly, researchers are aggressively pursuing novel therapies to treat kidney diseases before they result in end-stage renal disease. Stem cells and exosomes are among the most exciting and the most promising research topics in this area.
Most cells release tiny packets called extracellular
vesicles. The most notable extracellular vesicles are exosomes. While small,
exosomes are filled with high concentrations of potentially helpful substances
such as RNA, DNA, and proteins. While most cells release exosomes, researchers
are particularly interested in exosomes released by stem cells. It is within
these exosomes that stem cells pass along the substances that make stem cells
helpful in tissue repair and regeneration.
Zhang and
coauthors reviewed the recent advances that have been made using exosomes
to treat kidney diseases. Most of the work has focused on acute kidney injury
or AKI. Acute kidney injury can lead to
chronic kidney disease and kidney failure. Thus, if one could stop AKI, they
could potentially reduce the risk of chronic kidney disease.
Many different research groups have shown the power of
exosomes and other extracellular vesicles in treating acute kidney injury.
Exosomes taken from mesenchymal stem cells protected kidney cells from cell
death and fibrosis and helped them repair themselves. The
same was true of exosomes derived human umbilical cord stem cells.
Even stem cells taken from human liver cells were
able to improve kidney function after injury. There are manyotherexamples.
Gatti
et al. reported that extracellular vesicles derived from human adult
mesenchymal stem cells could protect against acute kidney injury, but, most
impressively, also halted the progression of AKI to chronic kidney disease.
This finding has important implications for people who suffer from serious
acute kidney illnesses, such as kidney ischemia. It means that—if confirmed in
human studies—stem cell-derived extracellular vesicles can help treat kidney
disease in the short term and reduce the risk of that illness becoming a
chronic, debilitating problem.
Further research is needed in this field but, initial
results confirmed by many laboratories have created well-founded enthusiasm for
the future.
Reference: Zhang, W. et al. (2016). Extracellular vesicles
in diagnosis and therapy of kidney diseases. American Journal of Physiology – Renal Physiology. 2016, Nov 1;
311(5): F844-F851.
Tissue injury is common to many human diseases. Cirrhosis results in damaged, fibrotic liver tissue. Idiopathic pulmonary fibrosis and related lung diseases cause damage to lung tissue. A heart attack damages heart tissue, just as a stroke damages brain tissue. In some cases, such as minor tissue injury, the damaged tissue can repair itself. Over time, however, tissue damage becomes too great and the organ itself can fail. For example, long-standing cirrhosis can cause liver failure.
One area of active research is to find ways to protect tissue from injury or, if an injury occurs, to help the tissue repair itself before the damage becomes permanent and irreversible. Indeed, tissue repair is one of the main focuses of regenerative medicine. Likewise, one of the most promising approaches in the field of regenerative medicine is stem cell therapy. Researchers are learning that when it comes to protecting against tissue injury and promoting tissue repair, exosomes harvested from stem cells are perhaps the most attractive potential therapeutic.
Why are stem cell exosomes so promising? Exosomes are small packets of molecules that stem cells release to help the cells around them grow and flourish. While one could inject stem cells as a treatment for diseases (and they certainly do work for that purpose) it may be more effective in some cases to inject exosomes directly. So instead of relying on the stem cells to produce exosomes once they are injected into the body, stem cells can create substantial amounts of exosomes in the laboratory. Exosomes with desired properties could be concentrated and safely injected in large quantities, resulting in a potentially more potent treatment for the disease.
Indeed, researchers have shown that extracellular vesicles (exosomes and their cousins, microvesicles) can be collected from stem cells and used to treat a variety of tissue injuries in laboratory animals.
Exosomes from the same type of stem cell protected the lungs and reduced lung blood pressure in mice with pulmonary hypertension.
Exosomes from endothelial progenitor cells protected the kidney from damage caused by a lack of blood flow to the organ.
In this growing field of Regenerative Medicine, research is constant and building as new science evolves from stem cell studies. Researchers are closing in on the specific exosomes that may be helpful in treating human diseases caused by tissue injury.
Reference: Zhang et al. (2016). Focus on Extracellular Vesicles: Therapeutic Potential of Stem Cell-Derived Extracellular Vesicles. International Journal of Molecular Sciences. 2016 Feb; 17(2): 174.
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