At our Anti-Aging and Regenerative Medicine Center in Thailand, we primarily utilize mesenchymal stem cells (MSCs) from diverse sources for our cellular therapy treatment protocols due to their remarkable regenerative properties and ability to promote tissue repair. By harnessing the power of MSCs, we aim to enhance our patients’ natural healing processes and improve their overall health and quality of life.
Mesenchymal Stem Cells (MSCs) are nonhematopoietic stem cells that are capable of differentiating into a variety of cell types.
MSCs are currently being evaluated in various pre-clinical and clinical studies and offer significant potential as a novel cellular therapy for tissue regeneration and repair.
They were first identified in bone marrow. They are a rare cell type and in BM they make up about 1 in 10,000 nucleated cells.
MSCs reside in diverse host tissue and organs, such as circulating blood, adult and fetal Bone Marrow, spleen, amniotic fluid, cartilage, muscle, tendons, placenta, adipose tissues, fetal tissues, trabecular bone, dental pulp, etc.
They are not immortal however they are capable of many population doublings in culture without loss of functionality. Age-related changes that could affect the biologic features of mesenchymal stromal cells (MSC), such as a decrease in proliferation and osteoblast differentiation capacity and an increase of senescence markers and apoptosis, have been reported recently.
When delivered systemically they migrate to sites of injury in animals. This property is called “homing”. MSC’s are regarded as nonimmunogenic. MSC exhibits low expression of histocompatibility complex (MHC) class I molecules and are negative for MHC class II antigens. They also show the ability to suppress T cell activation.
Malignant transformation is a potential risk with any cell therapy. The risk is high with embryonic stem (ES) cells and the newly discovered induced pluripotent (iPS) cells. Both ES and iPS cells are immortal in culture and can be expanded without limit. A defining characteristic of these cells is their ability to produce tumors when administered to animals. The risk of tumorigenicity is far less with cells from adult tissues.
If stem cells are expanded too many passages in culture, many cells from adult tissues display a limited lifespan in culture, and regularly progress to senescence. However, attention must be paid to culture conditions.
decrease in proliferation
decrease in differentiation capacity
increase in major histocompatibility complex (MHC II) molecules
increase of senescence markers and apoptosis
immunomodulation
anti-apoptosis
angiogenesis,
supporting the growth and differentiation local stem and progenitor cells,
anti-scarring and chemoattraction
self-renewal capacity
multi-lineages differentiation potential
homing and migration ability
immunomodulatory properties
and paracrine secretion activity
Dental pulp is the soft, connective tissue located in the central cavity of a tooth. It contains blood vessels, nerves, and specialized cells called odontoblasts that produce dentin, the hard tissue that makes up the bulk of a tooth [1][2][3].
Dental pulp is a rich source of mesenchymal stem cells, known as dental pulp stem cells (DPSCs). These stem cells have the ability to differentiate into various cell types, including odontoblasts, osteoblasts, chondrocytes, and neural cells [4][5].
Key features of dental pulp stem cells:
– Isolated from the dental pulp tissue of both permanent and deciduous teeth [4]
– Capable of self-renewal and multi-lineage differentiation [4][5]
– Express mesenchymal stem cell markers such as STRO-1, CD146, and CD44[5]
– Demonstrate high proliferative capacity in vitro [5]
– Able to form mineralized nodules and express odontogenic markers when induced to differentiate into odontoblasts [4]
– Exhibit angiogenic and neurogenic potential [5]
The unique properties of dental pulp stem cells make them a promising source for regenerative therapies in dentistry and beyond. Research is ongoing to explore their potential applications in tissue engineering, bone regeneration, and neural repair [4][5].
Dental pulp contains a population of multipotent stem cells that can be isolated and expanded for various therapeutic purposes, highlighting the importance of this tissue as a valuable source of adult stem cells.
Umbilical Cord (Wharton’s Jelly) is a gelatinous connective tissue found within the umbilical cord that surrounds and protects the blood vessels. It is named after the English physician Thomas Wharton, who first described it in 1656.
Wharton’s jelly is composed primarily of:
– Mucopolysaccharides, mainly hyaluronic acid and chondroitin sulfate [4]
– Collagen fibers
– Fibroblast-like cells
– Occasional mast cells [5]
It acts as a mucous connective tissue derived from the extra-embryonic mesoderm of the connecting stalk [4]. The tissue is divided into three regions based on the distribution of stromal cells and extracellular matrix components [1]:
1. Perivascular Wharton’s jelly: Most abundant in stromal cells, near the umbilical vessels
2. Intervascular Wharton’s jelly: Less abundant in stromal cells
3. Sub-amniotic Wharton’s jelly: Least amount of stromal cells, near the umbilical epithelium
Umbilical Cord Stem Cells (UCSCs)
Wharton’s jelly is a rich source of mesenchymal stem cells (MSCs), known as umbilical cord stem cells (UCSCs). These stem cells exhibit several unique properties:
– Express mesenchymal stem cell markers such as CD105, CD73, CD90, Oct-4, Sox-2, and Nanog [1]
– Capable of self-renewal and multi-lineage differentiation into various cell types, including osteogenic, adipogenic, and chondrogenic lineages [1]
– Demonstrate high proliferative capacity in vitro [1]
– Do not express MHC-II and exhibit immunomodulatory properties, making them suitable for allogeneic and xenogeneic transplantations [1]
Clinical Applications
UCSCs derived from Wharton’s jelly are a promising source for regenerative medicine and cellular therapies due to their stemness potency and immunomodulatory properties. Ongoing research explores their potential applications in tissue engineering, bone regeneration, and neural repair [1].
Wharton’s jelly is a unique and valuable component of the umbilical cord, providing structural support and serving as a rich source of mesenchymal stem cells with great potential for clinical applications in regenerative medicine.
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Amniotic Membrane (AM) is the innermost layer of the placenta and fetal membranes. It is a thin, avascular, and transparent tissue that serves as a protective barrier for the developing fetus. AM has been used therapeutically for over a century in various medical applications, particularly in ophthalmology and wound healing.
AM consists of a single layer of cuboidal to columnar epithelial cells attached to a basement membrane. The underlying stromal layer is relatively acellular and avascular. AM is composed of:
– Epithelial cells
– Basement membrane
– Stromal matrix
– Collagen types I, III, IV, V, and VI
– Fibronectin
– Laminin
– Proteoglycans
AM exhibits several beneficial properties that make it suitable for various medical applications:
– Anti-inflammatory: AM contains anti-inflammatory cytokines like IL-10 that downregulate pro-inflammatory cytokines.
– Anti-scarring: AM inhibits fibroblast proliferation and myofibroblast differentiation, reducing scar formation.
– Anti-microbial: AM possesses antimicrobial properties against various bacteria and fungi.
– Pro- or anti-angiogenic: AM can either promote or inhibit angiogenesis depending on the surface it is applied to.
– Tissue growth promotion: AM provides a conducive environment for epithelial cell migration, attachment, and proliferation.
AM is a rich source of mesenchymal stem cells (MSCs), known as amniotic membrane stem cells (AMSCs). These stem cells exhibit several unique properties:
– Express MSC markers like CD105, CD73, CD90, and CD44
– Capable of multi-lineage differentiation into various cell types, including osteogenic, adipogenic, chondrogenic, and neurogenic lineages
– Demonstrate high proliferative capacity in vitro
– Possess immunomodulatory properties, making them suitable for allogeneic transplantation
Clinical Applications
AM has been used in various medical fields, including:
– Ophthalmology: Treating ocular surface disorders, corneal ulcers, and perforations
– Wound healing: Promoting healing in chronic wounds, burns, and skin injuries
– Gynecology: Treating vaginal agenesis and adhesions
– Plastic surgery: Preventing adhesions and promoting healing after reconstructive procedures
– Gastrointestinal surgery: Preventing adhesions and promoting healing after intestinal anastomosis
Amniotic membrane is a versatile and valuable tissue with a wide range of applications in regenerative medicine and tissue engineering. Its unique properties and the presence of stem cells make it a promising source for various therapeutic interventions.
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Adipose tissue, commonly known as body fat, is a specialized type of loose connective tissue primarily composed of adipocytes, which are cells that store energy in the form of lipids. This tissue plays crucial roles in energy storage, thermal insulation, cushioning of organs, and serving as an endocrine organ that produces hormones and cytokines involved in metabolic regulation.
Adipose tissue can be categorized into two main types:
1. White Adipose Tissue (WAT):
– Predominant in adults, WAT is responsible for energy storage, insulation, and cushioning of vital organs.
– It contains large lipid droplets and is involved in the secretion of hormones such as leptin, which regulates energy balance and appetite.
2. Brown Adipose Tissue (BAT):
– More prevalent in infants, BAT is specialized for thermogenesis, generating heat by burning calories.
– It contains numerous mitochondria and smaller lipid droplets, contributing to its energy-burning capabilities.
Adipose tissue is not only a storage depot for fat but also a rich source of stem cells known as Adipose Tissue Stem Cells (ADSCs). These cells are part of the stromal vascular fraction (SVF) of adipose tissue, which includes various cell types such as preadipocytes, fibroblasts, and immune cells.
– Multipotency: ADSCs have the ability to differentiate into multiple cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells), and myocytes (muscle cells). This multipotency makes them valuable for regenerative medicine applications.
– High Yield: Compared to other sources of stem cells, such as bone marrow, adipose tissue provides a significantly higher yield of stem cells. Approximately 1 gram of adipose tissue can yield around 5,000 stem cells, which is about 100 times more than that obtained from an equivalent amount of bone marrow.
– Ease of Harvesting: ADSCs can be easily harvested through minimally invasive procedures like liposuction, making them more accessible than other stem cell sources.
– Immunomodulatory Properties: ADSCs possess immunosuppressive qualities, which can help in reducing inflammation and promoting tissue repair, making them suitable for therapeutic applications in autoimmune diseases and tissue regeneration.
ADSCs are being extensively researched and utilized in various clinical applications, including:
– Regenerative Medicine: Due to their ability to differentiate into various cell types, ADSCs are being explored for treating conditions such as osteoarthritis, cardiovascular diseases, and soft tissue injuries.
– Wound Healing: ADSCs can enhance wound healing processes by promoting angiogenesis (formation of new blood vessels) and tissue regeneration.
– Cosmetic Procedures: They are increasingly used in aesthetic medicine for fat grafting and facial rejuvenation, as they can improve skin quality and volume.
Adipose tissue serves multiple essential functions in the body, and its associated stem cells (ADSCs) are a promising resource for regenerative medicine, offering significant potential for therapeutic applications due to their multipotency, ease of harvesting, and immunomodulatory properties.
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Exfoliated human deciduous teeth, also known as baby teeth or milk teeth, are teeth that naturally fall out during childhood as the permanent teeth emerge. These teeth contain a unique population of stem cells called Stem Cells from Human Exfoliated Deciduous Teeth (SHED).
Mesenchymal Stem Cells (MSCs) were isolated from human exfoliated deciduous teeth. The selected MSCs could be sub-cultured under standard conditions for more than 30 passages. The MSCs, designated Dentachymal will be sub-cultured not more than 5 passages.
– SHED are a highly proliferative and clonogenic population of stem cells capable of differentiating into various cell types, including neural cells, adipocytes, and odontoblasts [1][2].
– After in vivo transplantation, SHED can induce bone formation, generate dentin, and survive in mouse brain while expressing neural markers [1][2].
– SHED are derived from an accessible tissue resource and can provide enough cells for potential clinical applications [1][2].
– These stem cells are negative for HIV-1, HBV, HCV, mycoplasma, bacteria, yeast, and fungi [3].
Characteristics and Potential Applications
– SHED have a high proliferative capacity, easy accessibility, multilineage differentiation potential, and low immunogenicity, making them a valuable source for regenerative medicine and tissue engineering[4].
– They can be successfully differentiated in vitro and in vivo into odontoblasts, osteoblasts, chondrocytes, adipocytes, and neural cells[4].
– SHED can remain undifferentiated and stable after long-term cryopreservation, allowing for potential banking and future therapeutic use[4].
– Conditioned medium derived from SHED (SHED-CM) has shown promising results in treating neurological disorders like amyotrophic lateral sclerosis (ALS) by reducing mutant SOD1-induced intracellular aggregates and neurotoxicity[5].
Stem cells from exfoliated human deciduous teeth are an accessible, versatile, and valuable source for regenerative medicine and tissue engineering applications due to their unique properties and therapeutic potential.
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