Use of Stem Cells in Urology and Andrology

Use of Stem Cells in Urology and Andrology

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In modern medicine, we are increasingly trying to use the most accurate and personalized medicine. What could be more personal than your stem cells that get into target organs and help them to resume their natural function?

A Bit of the Different Types of Stem Cells

Most cells in the human body have a narrow specialization, i.e., form a single type of cell. This determines the specifics of the formation of various tissues and organs with unique functions. There are more than 350 species of such cells in the human body. In the process of embryogenesis, especially in the early stages, the body’s cells do not yet have a narrow specialization. Still, they can differentiate and be the ancestor of different types of cells. Such cells are called stem cells. They are a versatile building material from which anybody’s cells are differentiated against specific biochemical reactions under the appropriate functional and anatomical environment.

These cells, primarily embryonic stem cells (ESCs), have proven promising not only for solving many fundamental issues of genetics and developmental biology but also in practical biotechnology, gene therapy, transplantation, hematology, veterinary medicine, pharmacotoxicology, drug testing, and other areas. Suppose ESCs are grown in culture, in vitro. In that case, they produce normal stem cells (undifferentiated, self-renewing) cells that can transform into different types of cells and tissues (hematopoietic, sex, muscle, nervous, etc.) and remain in cryopreservation for a long time.

Two Stem Cell Classifications Are Used

According to the source of the cells:

  • embryonic
  • fetal
  • bone marrow cells
  • umbilical cord blood cells
  • tissues of an adult organism

By differentiation ability:

  • Totipotent cells of all types
  • Pluripotent, forming cells of many kinds, but not all
  • Multipotent, including various types of cells
  • Unipotent, creating only one type of cell
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Cell differentiation and their normal development (proliferation and differentiation) control specific development genes. After the injury, a blastema (a cluster of cells capable of growth and regeneration) is formed at the site of damage. Then it is differentiated into specific types of cells, and the lost tissue is regenerated. Recent advances in tissue bioengineering have brought scientists closer to the ability to grow individual organs in the laboratory, suggesting an unprecedented level of personalized medicine that previously could only be read about in science fiction novels.

Reliable biomaterials are essential to help improve the results of surgical bladder enlargement, urethroplasty, surgical treatment of urinary incontinence, erectile dysfunction and elongation, augmentation, and reconstruction of the penis.

The cell approach involves using donor cells that are either used independently or with a matrix.

There are three potential cell sources:

  1. embryonic stem cells — associated with critical ethical issues, and they also retain allogenous potential.
  2. Gestational stem cells (from the umbilical cord, placenta, and amnion) — their extraction is more straightforward and associated with fewer ethical problems.
  3. Adult stem cells are derived from bone marrow, blood, fat/connecting tissue, and skeletal muscles — unlike other stem cells, they have low oncogenic potential and the greatest biosafety, and the ability to treat many diseases.

Stem Cells in Urology

  1. Urethral stricture is a common disease associated with a high level of relapse and the need for retreatment. Substitute urethroplasty involves implanting healthy tissue (such as the mucous membrane of the cheek) to improve results. However, limited tissue resources and donor tissue-related complications affect overall success rates.

    Raya-Rivera et al. took bladder tissue from five boys (average age 11 years) with urethra defects because of injury. They transplanted it to a synthetic polylactoglycolic acid (PLGA) matrix to create a new urethra. After three months, the matrix formed a standard urethra architecture with satisfactory functional results in all cases.

    Bhargava et al. demonstrated the development of an autologous tissue-engineered mucous graft because of the cultivation of only a few cells from the cheek mucosa. This technique is promising, even though most patients required further surgical modification. The results are commensurate with those achieved with existing materials, although the small number of participants and a short observation period are apparent limitations in these studies.

OUR CLINIC, IN ASSOCIATION WITH THE UKRAINIAN ASSOCIATION OF BIOBANKS, WILL ACHIEVE SUCCESS IN GROWING THE NEXT GENERATION OF URETHROPLASTY IN URETHRA STRICTURES

Also, now the Andrology Laboratory is studying the effectiveness of treatment of patients with stress incontinence by introducing pluripotent autologous stem cells into the sphincter area. They reproduce the function of a sphincter by growing the corresponding muscles.

Stem cells in the Treatment of Male Infertility

Another promising area is the administration of collagen with the patient’s stem cells to treat retrograde ejaculationassociated with the insufficiency of the locking mechanism, usually due to diabetic polyneuropathy, which causes sperm during sexual intercourse not to go forward but to be ejected back into the bladder. We have long used the method of introducing fillers — hyaluronic acid gel — into the posterior parts of the urethra to create a locking mechanism. However, any gel dissolves after one year, and the problem returns. The use of collagen and stem cells, which will then grow in this zone and contribute to its reinnervation, will solve the problem of retrograde ejaculation for an extended period (up to 3-6 years).

Also exciting is the treatment of male infertility by administering autologous stem cells in non-obstructive azoospermia, i.e., a situation where the testicles do not ultimately produce sperm because they do not have spermatogenic epithelium. In some cases, the testicular administration of stem cells into the parenchyma can restore sperm production, sensitivity to follicle-stimulating and luteinizing hormones, and improve testosterone synthesis, which can return lost fertility and improve sexual function.

Stem Cells in Andrology

The use of PRP therapy and autological stem cells to treat erectile dysfunction is highly effective. Erectile dysfunction can involve both a decrease in arterial inflow and an increase in the venous outflow. The introduction of VGF, a factor contributing to the growth of new vessels from PRP fraction, and the introduction of autologous stem cells contribute to the development and restoration of cavernous tissue of the penis and strengthens the venous-occlusion mechanism, which prevents venous leakage and restores the hardness of the erect penis.

Intracavernous injections of stem cells during operations to treat Peyronie’s disease are indispensable. The standard corporoplasty procedure involves the excision of the plaque and the resumption of the tightness of the protein shell of cavernous bodies. Large plaques form a significant defect in cavernous tissue, resulting in incomplete filling of this hollow body and erectile dysfunction and curvature of the penis. Often with large plaques, urologists immediately offer the installation of penile implants, even at an average level of preoperative erection. The introduction of stem cells during surgery and the postoperative period allows restoring the volume of cavernous tissue and normal erection after corporoplasty surgery, even without prostheses.

The use of stem cells in clinical methods of penile enlargement has also been very effective. The standard surgical extension of the penis provides for ligamentotomy surgery, which is 2-3 cm. The subsequent wearing of an extender stretches the penis by another 1.5-2 cm in 6 months. However, such a stretch should be carried out extremely carefully so as not to cause an overgrowth of the internal structures of the penis and, as a result, vein-occlusive erectile dysfunction. Monthly injections of autological stem cells contribute to the growth of cavernous tissue, and therefore faster and safer growth of the penis, which will increase the penis by a total of 5-7 cm and is an alternative technique for an initially small, less than 10 cm in an erected form, penis.

For penile thickening surgery, we most often use a polysaccharide matrix soaked in autologous stem cells or non-surgical administration of collagen and polylactic acid, also with stem cells. Fillers disappear after a while, but stem cells form structures that increase the penis by 3 cm in girth.

Patient stories

A patient from America with Peyronie’s disease: a pronounced plaque curving the penis.
The world practice is corporoplasty, in which the excised plaque is replaced by the bovine pericardium, which aligns the penis.

However, the patient wanted to thicken the penis at the same time. But here the rule applies: you cannot put two different implants (bovine pericardium and prolene mesh for thickening). Non-acceptance and rejection may occur.

For this patient we have grown from his OWN stem cells the mesothelium (a thin film), with which we have closed the defect of the tunica albuginea and aligned the penis. And a prolene mesh was installed under the skin, which added almost 4 cm in circumference.