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Stem Cell Therapy for Chronic Bladder Ischemia

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Stem cells help in tissue regeneration by providing progenitor cells and chemokines. They are capable of differentiating into new cell types.

Written by

Dr. Kavya

Published At September 14, 2022
Reviewed AtFebruary 16, 2023

Introduction

Among various problems associated with voiding dysfunction, stress urinary incontinence (SUI) and overactive bladder (OAB) are two of the challenges urologists face. Stem cell therapy shows a promising future in treating lower urinary tract dysfunction, erectile dysfunction, bladder trauma, and renal disease. Stem cells have a role in multilineage differentiation and self-renewal, which helps in tissue repair and regeneration. In addition, stem cells secrete bioactive factors such as anti-scarring, neovascularization, and antiapoptotic and immunomodulatory effects and direct the cells (progenitor and stem cells) to the site of injury.

What Are the Clinical Problems Associated With Urinary Incontinence?

Stress Urinary Incontinence in Women:

Involuntary leakage of urine due to the absence of bladder contraction resulting due to increased abdominal pressure. This happens when there is a failure of the pelvic floor muscles, urethral sphincter, and fascial tissues to provide closure. When Intra abdominal pressure exceeds urethral pressure, it leads to SUI. Incidence is higher in older women than compared in younger women. Urethral pressure depends on factors such as urethral sphincter musculature, bladder neck position, sphincter innervation, and vascular supply.

Pregnancy and Childbirth Are Risk Factors That May Cause Injuries Such as :

  1. Vascular damage due to fetal compression of pelvic structures.

  2. Injury to connective tissue during vaginal birth.

  3. Traumatic injury to pelvic muscles and nerves.

  4. Injury to the lower urinary tract during childbirth.

Treatment involves conservative approaches such as biofeedback, electrical stimulation, pelvic floor physiotherapy, and sometimes pharmacotherapy. Surgical modalities involve urethral slings and suspensions, artificial urethral sphincters, transurethral bulking agents, and bulbar urethral slings.

Stress Urinary Incontinence in Men :

Radical prostatectomy is one of the major causes of SUI in men. Post prostatectomy results from failure to store urine which is further caused by inadequate resistance of the outlet sphincter.

Overactive Bladder:

Around 12 % of men and women are affected by an overactive bladder. With increasing age, overactive bladder without urgency incontinence is common among older men, and OAB with urgency is common in females. Signs and symptoms include urgency, with or without urgency, incontinence, frequency, and nocturia. Treatment options involve pharmacological interventions such as anticholinergic drugs and beta-3 adrenergic. Non-pharmacological options involve biofeedback, behavioral and dietary modifications, and sacral neuromodulation.

What Are the Sources of Stem Cells?

Stem cells are divided into the following categories:

  1. Stem Cells Are Derived From Early-Stage Embryos (ESCs): They contain all adult cell types and are a pluripotent cell source, and have great therapeutic potential.

  2. Derived From the Placenta or Amniotic Fluid (AFPS): They are heterogeneous stem cell populations obtained from amniotic fluid and placental membrane, and they contain mesenchymal cells and multipotent AFPS that have renewal capacity. AFPS cells can be differentiated into all three germ layers, which include cells of osteogenic, myogenic, endothelial, adipogenic, hepatic, and neural lineages.

  3. Induced Pluripotent Stem Cells (IPSC): Have potency of multipotent differentiation and self-renewal. The disadvantages involve the time required in setting the cells in the pluripotent stage and also the time required to differentiate them into the desired lineage.

  4. Adult Stem Cells (ACS): These cells have been used in urologic applications. They help in acting on tissue-specific progenitors, which help in repairing damage and restoring functions. Multipotent adult progenitor cells (MCS) are a subset of adult stem cells which is obtained from bone marrow stroma and vascularized tissues such as the endometrium, kidney, adipose, and muscle.

  5. Urine-Derived Stem Cells (USC): These cells have potential in urologic applications and can be isolated from voided urine. They show features of multipotent differentiation, self-renewal, and clonogenicity. It can differentiate in multicell lineages at the cellular, gene protein expression, and tissue levels. Holds advantages in urinary incontinence and voiding dysfunction as a cell source.

What Is the Mechanism of Action of Stem Cells?

Stem Cell Homing:

The delivery of stem cells to the site of injury is called homing. The progenitor cells, along with multipotent adult progenitor cells, enter the systemic circulation and reach areas of acute injury along with chemokine gradients which help in regeneration and healing. The homing of stem cells depends on the leukocytic migration to hematopoietic stem cells, metastatic cancer cells, and injured tissue. The MSCs also help in cellular migration and homing by chemoattraction, adhesion to vascular endothelial cells, and transmigration across the endothelium to the site of injury. Integrins and selections help in the direction of migration and adhesion of cells, including the MSCs.

Stem Cell Differentiation:

Stem cell differentiation is one of the major factors considered for the treatment of various urological dysfunctions, such as voiding dysfunction and urinary incontinence. For example, in stress urinary incontinence, the MSCs restore function mainly by their ability to differentiate into multiple cell lineages and also play a major role in the regeneration process.

How Is Stem Cell Therapy Used for Voiding Dysfunction?

Stem Cells for Stress Urinary Continence:

Voiding dysfunction causes damage to the surrounding muscles and nerves responsible for urinary incontinence. Several studies have been conducted to analyze the mechanism of injury to the continence mechanism; they include:

  1. Stimulation of nerve injury by pudendal nerve crush (PNC).

  2. Stimulation of anatomic nerve support with pubourethral ligament injury or urethrolysis.

  3. Stimulation of intrinsic urethral defects with periurethral cauterization, urethral sphincterotomy, or pudendal nerve transection.

  4. Combination of both voiding dysfunction and pudendal nerve crush.

In studies conducted on animals, medals show the efficacy of MSCs and ADSCs for mechanical, nerve, or external urethral sphincter injury. For example, in a study conducted by Kim et al., MDSCs were injected into the urethra of rats that had pudendal nerve dissection. Four weeks after the MDSCs, the urethral closure pressure was restored, and the injected MDSCs stained positive for muscle-specific markers, which helped in the repair of damaged muscle tissue.

Stem Cells for Overactive Bladder:

In a study conducted by Lee et al., 2012 MSCs with nanoparticles were injected into the bladder wall of rats following partial bladder outlet obstruction. It was followed up by histology, magnetic resonance imaging, and functional tests. It increased TGF-β protein and collagen factors. The study concluded that MSCs restore bladder function in rats with bladder outlet obstruction.

Conclusion

Stem cell therapy shows a promising future in urological complications such as voiding dysfunction and urinary incontinence. Applications have shown a success rate in animal clinical trials. With limited treatment to urological complications, its approach towards it through cell regeneration and differentiation will help in a better prognosis.

Frequently Asked Questions

1.

How Does Stem Cells Benefit Patients With Interstitial Cystitis?

Stem cells have the potential to help patients suffering from interstitial cystitis. In addition, the bladder can benefit significantly from the potent anti-inflammatory properties of fat-derived stem cells. This also encourages bladder healing.

2.

What Are the Diseases That Can Be Cured Using Stem Cells?

It is possible to direct stem cells to differentiate into particular cells used in people to regenerate and repair tissues that have been harmed or impacted by illness. Spinal cord injuries, Parkinson's disease, type 1 diabetes, amyotrophic lateral sclerosis, heart disease, Alzheimer's disease, burns, cancer, stroke, and osteoarthritis are among the conditions that stem cell therapies may help.

3.

What Are the Different Types of Stem Cell Therapy?

Autologous and allogeneic stem cell transplants are the two main types of stem cell therapies. In an autologous transplant, stem cells are taken from the patient's blood and administered once the treatment has eliminated the cancerous cells. An allogeneic transplant uses stem cells from a different patient. Induced pluripotent stem cells (iPSCs), embryonic stem cells (ESCs), and adult stem cells (ASCs) are the main types of stem cells. Adult stem cells include neural stem cells (NSCs), hematopoietic stem cells (HSCs), skin stem cells (SSCs), and mesenchymal stem cells (MSCs).

4.

How Quickly Does Stem Cell Therapy Heal?

Some patients report starting to feel better in just a few days. However, the patient may experience stiffness and soreness in the affected joint, in addition to some mild pain from the site of the stem cell extraction, for one to two weeks following the procedure. Patients typically report slowly increasing relief from their symptoms over the following months after the initial few weeks of recovery. Many patients only need one treatment session, and stem cells can continue to heal the damaged area for up to a full year after the initial procedure.

5.

What Are the Risks Associated With Stem Cell Therapy?

Stem cell therapy carries some risks, such as immune rejection of the cells, just like any other form of medical care. However, the great promise of stem cells is that they can divide repeatedly and differentiate into a wide variety of cell types. Ironically, stem cells can also develop tumors because of these capabilities. This potential risk necessitates that medical professionals and patients proceed cautiously, making it imperative that more research be done.

6.

Describe Chemokines and Provide Some Examples.

Chemokines are tiny protein molecules that the immune system's cells produce. These serve as chemoattractants, causing immune cells to migrate to an infection site where they can target and eliminate invaders like microbes. Chemokines are also crucial for biological processes like morphogenesis and wound healing because of their significant contribution to the activation of host immune responses. They also play a vital role in the pathogenesis of diseases like cancer. A few examples include CCL2 (chemokine ligand 2), CCL3, CCL5, CCL14, CCL19, CCL20, CCL21, and CCL11.

7.

What Are the Characteristics of Inflammatory Chemokines?

Inflammatory chemokines are a type of chemokine and are produced in pathological settings (in response to pro-inflammatory stimuli like IL-1 (interleukin 1), TNF-alpha (tumor necrosis factor), LPS (lipopolysaccharides), or viruses) and actively contribute to the inflammatory response by drawing immune cells to the site of inflammation. Following are some examples: CXCL-8, CCL2, CCL3, CCL4, CCL5, CCL11, and CXCL10.

8.

What Are the Symptoms of Bladder Dysfunction?

Typical symptoms of bladder dysfunction include:
- Persistent and an intense urge to urinate.
- A burning sensation and pain while urinating.
- Bladder leakage.
- Frequent urination in small amounts.
- Urine that smells strong.
- Bloody urine.
- Pain during sexual intercourse.
- Cloudy urine.

9.

What Are the Signs of Permanent Bladder Damage?

The muscles in the bladder may suffer permanent damage and lose their capacity to contract properly if they are stretched excessively or for an extended period of time. Bladder injury also results from pelvic fractures less than one in ten times. Blood in the urine, difficulty urinating, and pain in the pelvis and lower abdomen before or after urinating are the most typical signs of a bladder injury.

10.

How Is Stress Incontinence in Men Treated?

A combination of approaches to treating incontinence is usually suggested. The stress incontinence episodes might be reduced or eliminated with the help of behavior therapies. This include:
- Kegel exercises and other exercises for the pelvic floor.
- A sufficient amount of fluid intake.
- Bladder training.
- Losing weight, quitting smoking, or treating a persistent cough.
Surgical procedures to treat stress incontinence aim to support the bladder neck or enhance sphincter closure. Options for surgery include: 
- Sling procedure.
- Injectable bulking agents.
- Retropubic colposuspension. 
- Inflatable artificial sphincter.

11.

Does Stem Cell Therapy Have Any Disadvantages?

The efficacy of stem cell therapy can vary based on the medical condition treated. The cells have the potential to repair diseased cells, however, the effectiveness is influenced by factors like the type of stem cells and the method of administration. More research is required to understand the therapeutic potential of stem cells.

12.

Is Permanent Bladder Damage A Medical Condition?

Permanent bladder damage may occur due to underlying causes or factors. It refers to permanent bladder damage and may lead to urinary tract infection and chronic inflammation. The condition is also observed in patients with urinary stones. Leading to bladder obstruction. Other causes include neurological disorders, bladder cancer, and spinal cord injury.

13.

Does Stem Cell Therapy Have A Success Rate?

The success rate of stem cells depends on the condition being treated. In some individuals, the results are promising, and the outcomes are successful. However, the success rate may vary depending on the type and quality of stem cells. Stem cell therapy is used in combination with comprehensive treatment, hence it is better to approach with realistic expectations.
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Dr. Samer Sameer Juma Ali Altawil
Dr. Samer Sameer Juma Ali Altawil

Urology

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