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Stem Cell Applications in Exosome Treatment at Liv Hospital

Exosomes are natural vesicles released by cells into the extracellular environment, ranging in size from 50 to 200 nanometers. Enclosed within a double-layered phospholipid membrane, these vesicles contain diverse types of nucleic acids and their derivatives, lipids, and proteins. They function as a communication network in the body, facilitating signaling between cells, transporting materials, and contributing to tissue healing processes.

Reasons for Exosome Secretion

  • Intercellular Communication
  • Genetic Material Transfer
  • Tissue Regeneration
  • Protective Function

Formation of Exosomes 

In the initial stage of exosome formation, the cell membrane undergoes endocytosis, wherein a portion of the membrane is internalized. This inward folding forms a small vesicle known as an intraluminal vesicle. Subsequently, multiple intraluminal vesicles accumulate within a structure called a multivesicular body (MVB). Fusion events between multivesicular bodies and the plasma membrane result in the release of MVB contents outside the cell.

These released microvesicles are termed “exosomes”. Each of these processes is intricately regulated by cellular signaling mechanisms.

Advantages of Exosome

  • Exosomes influence target cells by transmitting signals through the biomolecules they carry.
  • Enclosed within a thin membrane, they facilitate easy transport to different tissues and organs throughout the body.
  • Exosome therapy holds promise for expediting tissue repair and enhancing healing processes.
  • Moreover, their small size, typically ranging from 100 to 150 nm, enables them to effectively traverse the blood-brain barrier.

Exosome Production

Exosome production is a complex and meticulous process that typically spans 1-2 weeks and necessitates specific laboratory conditions.

Umbilical cord-derived mesenchymal stem cells are cultured and expanded in a cGMP (current Good Manufacturing Practices) compliant laboratory using suitable methods. Once an adequate cell population is attained, the cells undergo stress induction through various methods to stimulate exosome production.

The resultant exosomes are then purified using appropriate techniques. The final exosome product is stored in a sterile cold chain as a homogeneous suspension.

Quality Control – GMP Laboratory

Ensuring high-quality standards for exosome production is crucial for their safe application. At LivMedCell Regenerative Medicine, Stem Cell Center, our laboratory adheres to rigorous quality control measures for our exosome products. These include:

  • Mycoplasma Analysis
  • Endotoxin Test Analysis
  • Microbial detection and Gram staining
  • Flow Cytometry Analysis
  • NTA (Nanoparticle Tracking Analysis)

These tests are conducted under the supervision of specialized medical professionals. Furthermore, our exosomes are manufactured in a GMP-compliant facility approved by the Ministry of Health, ensuring stringent laboratory conditions.

Liv Hospital Regenerative Medicine Stem Cell Production Center, which has International Good Manufacturing Practices (GMP) quality standards, is the first center in Turkey where stem cell production is carried out at international standards and hospital conditions.

Exosome Applications

  • Acute Lung Injury
  • Graft versus Host Disease
  • Hair Loss
  • Spinal Cord Injury
  • Duchenne Muscular Dystrophy
  • Regulation of T and B Cells
  • Wound Healing Treatment
  • Photo-aging
  • Atopic Dermatitis
  • Skin Rejuvenation
  • Osteoarthritis
  • Spot Treatment
  • Muscle and Tendon Injury
  • Ligament Injury
  • Bone Healing
  • Joint Calcification
  • Cartilage Damage

Exosome Therapy for Skin Damage

The treatment of scars, spot imperfections, photoaging, and skin rejuvenation are biological responses to skin deformations.

Exosomes derived from mesenchymal stem cells:

  • Stem cell-derived exosomes possess the capability to repair scars.
  • Stem cell-derived exosomes effectively contribute to scar tissue revision.
  • Stem cell-derived exosomes facilitate the restoration of the skin’s elasticity and strength, and aid cells in regaining properties lost due to aging, leveraging their regenerative capabilities.

Exosome Therapy for Hair Loss

Hair loss has become increasingly prevalent among both men and women in recent years, attributed to various factors. Currently, numerous methods are employed to decelerate or halt hair loss and promote the regeneration of new hair follicles. However, many of these methods incorporate chemical drugs, often resulting in adverse effects.

  • Stem cell-derived exosomes offer a promising alternative. They can stimulate dormant hair follicles, thereby promoting the growth of new hair and effectively slowing or preventing hair loss, all without the associated side effects of chemical treatments.
  • Stem cell-derived exosomes accelerate the transition of hair follicles from the telogen phase to the anagen phase, facilitating the growth of new hair. Furthermore, these exosomes are recognized for enhancing cell viability, increasing the expression of growth factors such as insulin-like growth factor (IGF1) and keratinocyte growth factor (KGF), and promoting hair shaft elongation in human hair follicles. 

Exosome Therapy in Immune System Disorders

According to research findings, exosomes have demonstrated various mechanisms for activating the immune system.

  • Exosomes have been observed to effectively induce macrophages to release specific pro-inflammatory cytokines and enhance the secretion of tumor necrosis factors (TNFs).
  • Exosomes are recognized for their role in transporting major histocompatibility complex (MHC) peptide molecules and facilitating antigen presentation.
  • It is also reported that exosomes derived from stem cells support the immune system by promoting the activation of regulatory T cells.

Exosome Therapy for Graft vs Host Disease

It is a clinical condition that arises following tissue, cell, or organ transplantation, triggered by the immune response elicited by donor cells in the recipient.

Dry eye induced by graft-versus-host disease (GvHD) develops due to immune system reactions. In affected patients, its impact has been noted to diminish following the administration of stem cell-derived exosomes.

Stem cell-derived exosomes are employed preventively in the management of GvHD.

Exosome Therapy for Ovarian Rejuvenation

Premature ovarian aging has become increasingly prevalent in contemporary society. This condition is commonly associated with urban lifestyles, smoking, alcohol consumption, stress, autoimmune diseases, premature menopause following chemotherapy, and natural ovarian aging.

In recent years, substantial evidence has emerged supporting the efficacy of cellular therapies for such conditions. Additionally, exosome applications produced under cGMP (current Good Manufacturing Practice) conditions and administered into the ovaries have shown promising results.

Stem cell-derived exosomes have demonstrated beneficial applications in various conditions including polycystic ovary syndrome, ovarian development disorders, uterine diseases, and enhancing endometrial receptivity.

Exosome Therapy for Male Infertility

  • Stem cell-derived exosomes have been shown to reduce reactive oxygen species (ROS) production and their impact on sperm.
  • These exosomes have the potential to enhance sperm quality.
  • Studies have highlighted the significant potential of stem cell-derived exosomes in restoring spermatogenesis and promoting sperm regeneration.
  • Stem cell-derived exosomes can serve as a supplement for stored sperm in in vitro fertilization treatments.
  • Moreover, they mitigate testicular torsion damage by preventing apoptosis in spermatogenic cells through the promotion of their proliferation and migration.
  • Additionally, they facilitate the healing process of spermatogenic processes and germinal tubules.

Exosome Therapy for Spinal Cord Injuries

Exosomes derived from Stem Cells have demonstrated effective reparative effects in spinal cord injuries (SCI).

Exosomes derived from stem cells:

  • Accelerate motor function recovery and mitigate histopathological damage by promoting neuronal regeneration.
  • Suppress apoptosis of neuronal cells and support functional recovery.
  • Enhance locomotor functional recovery and reduce inflammation.
  • It enhances functional recovery and reduces complement activation resulting from spinal cord injury.
  • Improve functional recovery and promote axonal regeneration.
  • Repair spinal cord injury deformities through the contained miRNA-21, miRNA-133b, and miRNA-126.

Exosome Therapy for Orthopedic Diseases

Cartilage Damage and Joint Calcification: Exosomes derived from stem cells promote the regeneration of cartilage tissue. They mitigate inflammation and enhance the proliferation of cartilage cells. This therapy is employed in treating joint disorders such as osteoarthritis and talus.

Muscle and Tendon Injuries: Stem cell-derived exosomes expedite the healing process of muscle and tendon injuries. They reduce inflammation associated with conditions like tendinitis and tendinosis, and facilitate the rapid regeneration of tendon cells.

Bone Healing: Exosomes derived from stem cells accelerate the healing of fractures. They promote the regeneration of bone tissue by stimulating the activity of osteoprogenitor cells.

Ligament Injuries: Stem cell-derived exosomes stimulate the regeneration of connective tissue, specifically ligaments. This treatment facilitates swift recovery from sports injuries and other traumatic conditions.

Exosome Therapy for Intervertebral Disc Degeneration

 Stem cell-derived exosomes containing miR-410 can alleviate the severity of intervertebral disc degeneration.

These exosomes slow down the progression of intervertebral disc degeneration and may delay matrix degradation.

Furthermore, stem cell-derived exosomes can regulate apoptosis related to Endoplasmic Reticulum stress.

Exosome Therapy for Athlete Diseases

Anterior Cruciate Ligament Reconstruction: Stem cell-derived exosomes facilitate tendon-bone healing by regulating the polarization of M1/M2 type macrophages during Anterior Cruciate Ligament Reconstruction.

Rotator Cuff Injuries: Stem cell-derived exosomes promote rapid healing of tears and reduce the incidence of re-tearing post-surgery.

Shoulder Stiffness: Exosomes have demonstrated the ability to suppress TGFBT1 expression through miRNA-let-7a-5p, thereby halting the progression of adhesive capsulitis and alleviating associated pain.

Achilles Tendon Injury: Stem cell-derived exosomes aid healing by modulating mechanisms that balance tendon extracellular matrix synthesis and degradation, thereby accelerating the recovery process and reducing inflammation.

Exosome Therapy for Retinal Diseases

Retinitis Pigmentosa: Stem cell-derived exosomes promote the survival of retinal ganglion cells and aid in axon regeneration. They also help to partially prevent axon loss and dysfunction in retinal ganglion cells.

Optic Atrophy: Stem cell-derived exosomes promote axon regrowth by secreting neuroprotective compounds. They protect retinal ganglion cells (RGCs) and facilitate their integration into existing neural networks, enabling them to reestablish neural connections.

Age-Related Macular Degeneration: Stem cell-derived exosomes inhibit the apoptosis of photoreceptor cells, maintain normal retinal structure, and exert anti-inflammatory, neuroprotective, and anti-apoptotic effects.

Exosome Therapy for Parkinson’s Disease

Stem cell-derived exosomes have the potential to reduce the death of dopamine neurons in Parkinson’s disease.

Because these exosomes can easily cross the blood-brain barrier, they enhance dopamine secretion in the brain.

Moreover, stem cell-derived exosomes contain miRNA known for its neurorestorative effects observed in ischemic stroke, suggesting they can induce beneficial changes in the surrounding environment.

Additionally, these exosomes suppress apoptosis, promote cell proliferation, and facilitate angiogenesis, thereby potentially offering significant therapeutic benefits in degenerative diseases like Parkinson’s.

Exosome Therapy for Diabetic Foot

Stem cell-derived exosomes may facilitate the treatment of tissue damage by reducing inflammation.

These exosomes can promote tissue healing by regulating the polarization of M1/M2 type macrophages.

Moreover, stem cell-derived exosomes containing miRNA-181c-5p can alleviate neuropathic pain caused by chronic constriction injury by reducing neuropathic inflammation.

Exosome Therapy for Peripheral Neuropathy

Stem cell-derived exosomes can improve decreased nerve conduction velocity associated with peripheral neuropathy.

These exosomes can enhance nerve fiber count, myelin thickness, and axon diameter in sciatic nerves.

Furthermore, stem cell-derived exosomes promote functional recovery by alleviating neurovascular dysfunction in patients with peripheral neuropathy, achieved through the suppression of pro-inflammatory genes.

Exosome Therapy for Lung Diseases

Idiopathic Pulmonary Fibrosis: Stem cell-derived exosomes may alleviate respiratory compromise caused by fibrosis. They can reduce alveolar damage and fibrotic scarring.

Chronic Obstructive Pulmonary Disease (COPD): Stem cell-derived exosomes may alleviate shortness of breath associated with COPD. They might also reduce lung inflammation and damage from cigarette smoke, as well as protect against bronchial epithelial damage caused by toxic fumes.

Age Limit

There is no specific age limit for exosome therapy; however, the effectiveness and suitability of the treatment may vary depending on individual factors and health conditions.

Side Effects

The product does not interact with medications and has no known side effects. However, its safety during pregnancy and breastfeeding has not been tested.

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