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Stem cells

Stem cells are capable of self-renewal as they can divide numerous times and maintain their undifferentiated state. They can be pluripotent or multipotent, as they have the potential to differentiate into several different adult cell types. Stem cells are able to repair or regenerate damaged tissues. Interestingly, even after our birth and into adulthood, every tissue in our body harnesses a store of these stem cells.

Adult stem cells are multipotent, which can produce more limited cell types than embryonic stem cells. Since adult stem cells can be harvested from and used for the same patient, both immunogenic rejection and ethical controversy can be precluded.  As a result, scientists and clinicians are excited about the role of stem cells to treat various diseases, injury, and the deterioration of tissues due to aging or trauma. The growing number of clinical trials and available scientific data raises the expectation of clinicians delivering future treatment procedures using stem cells.

There are two broad types of stem cell:

  1. Pluripotent stem cells like embryonic stem cells (ESC) derived from embryos and induced pluripotent stem cells (iPSC) derived by reprogramming adult tissue cells or blood cells. These cells can be differentiated into all cell types in the body and hence possess huge therapeutic potential. However, ESC continue to be contentious because they are derived from embryos and will remain allogeneic and likely to be rejected. However, iPSC are also pluripotent and can produce all cell types in our body, albeit can be autologous and less likely to be rejected if used for transplantation purposes. Both ESC and iPSC can form tumours if not differentiated fully to adult cell types.
  2. Adult Stem Cells like Hematopoietic stem cells (HSC) derived from blood cells and are typically found in bone marrow or umbilical cord blood and Mesenchymal stem cells (MSC) generally derived from bone marrow, fat tissue and dental pulp tissue from teeth. These adult stem cells are multipotent and have limited differentiation potentials but less controversial than ESC for developing therapeutics.

What are iPSCs:

Embryonic stem cells (ESC) derived from embryos are naturally pluripotent (i.e. they can differentiate into any cell type). In 2006, Shinya Yamanaka found a new way to ‘reprogram’ adult cells and turn them into pluripotent stem cells, called induced pluripotent stem cells (iPSC). This procedure of generating laboratory-grown pluripotent stem cells allows any dividing cell in the body to become an iPS cell. The most common sources of iPS cells are adult skin or blood cells (Fibroblasts or PBMCs) that are genetically reprogrammed by forced expression of some or all of the genes – Oct4, Sox2, Klf4 and c-Myc.

Advantages:

The primary advantages of iPSCs compared to other stem cells are: That they are able to self-renew and differentiate into any cell lineage, and can be obtained using minimally invasive, low-risk procedures; thus, overcoming ethical issues and immune rejection associated with the use of ESC.

Since iPSCs carry the inherent ability to develop into any cell type, patient-specific cell lines can be generated which can help model human diseases (a reconstruction of the disease-state in the laboratory using patient-derived iPSCs) and for gene therapy.

Additionally, patient-specific iPSCs can be differentiated into any cell type and transplanted to the site of injury or disease-degenerated tissue, and are used in tissue engraftment.  iPSC technology is a powerful tool to test new pharmaceutical drugs, toxic compounds and hazardous chemicals for toxicity and side effects in a patient-specific manner. Thus, iPSCs have extensive applications in regenerative medicine, disease modelling and drug screening [1, 2].

iPSC conversion to MSCs:

Use of Mesenchymal stem cells (MSCs) in tissue regeneration is preferred over other approaches because they constitute a stem cell niche, support growth of tissue-specific stem cells, are hypoimmunogenic and are able to differentiate into cells of three lineages: osteogenic, chondrogenic and adipogenic. The promising therapeutic potential of MSCs is hampered owing to limitations in their proliferative potential, loss in their ability to differentiate over time, and replicative senescence in vitro.

Controlled differentiation of patient-specific iPSCs into MSCs or cells resembling adult MSCs is a distinguished approach to obtain a source of progenitor cells that can differentiate into any tissue and are clinically relevant owing to circumventing their aging-associated drawbacks.

The approaches to drive MSC-like differentiation from iPSCs are elegant, and can be achieved by supplementing the culture medium with a cocktail of growth factors, or by formation of Embryoid Bodies (EB), or by serial passaging of cells growing in culture.

Mesenchymal Stem Cells (MSCs)

Adipose tissue derived stem cells (ADSCs)

Zuk and co-workers3 introduced a multipotent and self-renewing progenitor cell population isolated from adipose tissue. ADSC’s have become a popular source of stem cells due to ease of accessibility to procure subcutaneous adipose tissue by a minimally invasive method, the simple isolation procedure, stem cell quality and proliferation capacity. More recently, ADSCs secreted cytokines have shown great potential in a variety of clinical applications as a cell-free way for regenerative medicine therapies including skin regeneration and wound repair, neurodegenerative disease and joint osteoarthritis.

Dental tissue derived stem cells (DPSCs)

Dental pulp stem cells (DPSC) are adult stem cells obtained from the dental pulp tissue in the tooth chamber. Since the discovery of Dental pulp stem cells in 2000, dental pulp tissue within the wisdom teeth in adults have become an important source of stem cells. Stem cells located within the pulp tissue can be isolated and stored for stem cell-based therapies. Additionally, the efficacy of these cryopreserved wisdom dental stem cells has been validated by few studies showing that the viability and clinical potential after both short and long-term storage remains unaffected.  For these reasons dental stem cells make a popular source for banking and clinical applications in the future.

Publications

Download latest publication: Wound Healing Study

Clinical Applications and banking possibilities for Mesenchymal stem cells

Stem cells biobanking

Through partnership with doctors and dentists and their collaboration, following proper screening and consent, patient clinical samples are obtained for processing and stored in the collection kit, which is optimized to maintain the viability of the tissue and transfer of the samples to the laboratory.  Rapid transfer of tissue to the laboratory is a critical factor in the success of stem cell biobanking.

Osteoarthritis

Osteoarthritis (OA) is a degenerative and inflammatory joint disease resulting in the degradation of joint cartilage. The available treatment options provide symptomatic relief but do not reverse chondral loss, leading to future pain and disability. Mesenchymal stem cells (MSCs) have been successfully recruited in pre-clinical and clinical models, aiming to regenerate the tissue. MSCs via release of essential cytokines that aid in regeneration and repair of degraded tissue. Moreover, the functional improvement reported in several clinical trials indicate that MSC therapy represents an exciting advancement in the treatment of OA leading to pain reduction and potential articular cartilage regeneration.

Skin regeneration

The skin is the largest organ in the body and contains stem cells that are indispensable for skin renewal. These stem cells also contribute in wound repair, resulting in restoration of tissue integrity and function. Skin ageing is a biological process where cells are no longer able to maintain normal skin thickness, strength and function. Skin stem cell biology has the potential to provide key insights into the mechanisms of regeneration of the epidermal tissue. Ongoing clinical studies, on the applicability of stem cells such as epidermal stem cells and mesenchymal stem cells from adipose tissue brings promise for development in clinical skin regeneration and repair process. Recently the secretory products derived from these cells; conditioned media and exosomes are being used to develop cell-free cosmeceuticals and therapeutics taking the controversy of stem cells away.

Neurodegenerative diseases

The central nervous system being the most sophisticated and least understood system of the human body, its disorders/diseases (such as Alzheimer’s disease – AD and Parkinson’s disease – PD) usually lead to an irreversible deterioration of the structure and function of nervous tissue, and is often accompanied by serious cognitive or physical loss in affected patients. Progress in understanding the molecular basis of neurodegenerative disorders is impeded as brain tissue samples are not easily available. iPS cells address issues of limited cell sources, inherent complexity of the human brain, and ethical constraints, all of which interfere with understanding disease onset and mechanisms. Patient-derived iPSCs can be reprogrammed into brain cells to mimic and study the diseased state, or disease-free iPS cells can be used for gene targeting to repair disease-causing mutation. A notable potential of iPSC technology is the differentiation into 3D organoid structures, that aid drug screening and toxicity studies. Although in its initial phase, iPS cell technology has the potential to aid neurodegenerative disease studies and also their treatment4. There are many more applications of stem cells that are being tried through clinical development for diseases that are untreatable at the moment and the scope is broadening with new discoveries in this field.

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References:

  1. Takahashi K, Yamanaka S. Induced pluripotent stem cells in medicine and biology Development 2013 140: 2457-2461
  2. Sidhu K. S. New approaches for the generation of induced pluripotent stem cells. Expert Opinion on Biological Therapy 2011 11, 569-79.
  3. Zuk PA, Zhu M, Ashjian P, et al. Human adipose tissue is a source of multipotent stem cells. Mol Biol Cell. 2002;13(12):4279–4295.
  4. Sidhu, K. S. Induced pluripotent stem cells a slippery slope for neurodegenerative disease modelling? The Open Stem Cell Journal Suppl. 2011 Issue 3, 46-51.