Stem Cells and Regenerative Medicine
WHAT ARE STEM CELLS?
Stem cells and nanotechnology collaborate in regenerative medicine, using nanomaterials for targeted delivery and enhancing stem cell potential in tissue engineering. The contribution of stem cells to modern medicine is of paramount importance, both for their broad use in basic research and for the opportunities they give us to develop new therapeutic strategies in clinical practice. Their characteristics make them valuable in a wide range of applications in the biological and medical sciences. For example, embryonic stem cells (ESCs) are excellent tools to understand human development and organogenesis. Stem cells such as iPSCs (induced pluripotent stem cells) will be critical in the investigation of new and safe therapies. In addition, stem cells may be able to replace damaged tissue or even regenerate organs. iPSCs provide the opportunity to set up human models of diseases that would improve the understanding of the pathogenetic mechanisms of human diseases and would enable improvements in cell-based therapy for degenerative disorders.
WHY STEM CELLS?
Stem cells give rise to all other cells with specialized tasks from existing cells where clonality can be seen- they generate new cells called daughter cells after division in the laboratory or under the correct conditions in the body. They have the ability to self-renew, can differentiate into a variety of cell types, or potencies, and can be utilized to replace tissues that have been destroyed. Although there are various uses of stem cells, a few are: bone marrow transplants, tissue engineering, gene therapy, treatment for ocular disorders, wound healing, dental applications, neurological disorders, and cardiovascular repair.
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The most important properties of stem cells are:
1. Self-renewability (ability to multiply widely)
2. Clonality (usually due to a single cell)
3. Efficiency (ability to differentiate into different cell types)
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Stem cells, known for their pluripotency, play a crucial role in repairing organ damage in postnatal and adult life. They can renew themselves by dividing and developing into the three main cell groups in the human body: ectoderm, which gives birth to the skin and nervous system, and endoderm, which forms the digestive tract, respiratory tract, endocrine glands, liver, and pancreas.
Stem cells have the potential to act like saviors in multiple scenarios. In regenerative medicine, stem cells are used to repair or replace damaged tissues and organs in the body, offering potential treatments for conditions such as heart disease, Parkinson's disease, spinal cord injuries, and diabetes. In drug development and testing, stem cells are used in drug screening to study the effects of new drugs on specific cell types, offering a more accurate and ethical way to test potential treatments. Stem cells in bioprinting are utilized to create living, functional tissues and organs. They hold immense potential for regenerative medicine, enabling personalized treatments and addressing organ shortages. Bioprinting with stem cells aims to revolutionize healthcare by offering groundbreaking solutions for tissue repair and replacement. Stem cells and nanotechnology collaborate in regenerative medicine, using nanomaterials for targeted delivery and enhancing stem cell potential in tissue engineering. To protect stem cells, cryopreservation is a technique used to preserve them at very low temperatures, typically in liquid nitrogen, to keep them viable for long periods of time. It enables the storage of stem cells for future use in regenerative medicine and research, offering a valuable resource for potential therapies and scientific advancements.
3D Bioprinting Using Stem Cells
Using a computer-generated design, 3D printing, sometimes called additive manufacturing, is a technique for building three-dimensional objects layer by layer. This can be achieved by several techniques where the material is brought along, often layer by layer, and then the deposition, bonding, or solidification is controlled by computers.
It utilises additive manufacturing techniques to create bioengineered tissues and structures using cells, substances, and biomaterials. This method uses models to create "bioink," a combination of biological and inorganic components. By precisely positioning biological components, biochemicals, and living cells, 3D bioprinting allows for the printing of tissue and organ models, enabling drug and therapy research. New techniques include layer-by-layer cell and hydrogel layering, bioprinting extracellular matrix, and scaffold printing for 3D bioprinting, restoring ligaments and joints.
The concept of SWIFT, short for functional tissue transfer, involves using stem cells in organ tissues to create grafts, implants, and supporting organs. This is a new bioprinting technique that makes use of bio-ink, to create models. Living cells are used as matrices, and 3D-printed blood vessels are printed on them. The 3D-printed material is then removed using heat, leaving channels for blood flow. SWIFT technology bypasses the need for cells to mature in a bioreactor and lacks the true density of human tissue. This innovative approach to 3D printing offers a more efficient and effective way to create functional organs.
Working principle of 3D bioprinting
Let's take a few examples to highlight how 3D bioprinting works.
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3D bioprinting of heart tissue: It starts with an MRI, the heart is scanned, and doctors take blood samples from the patient. The blood cells in the sample are modified to produce induced pluripotent stem cells (iPS). Because cells in the body have the same number of genes and the same composition, they can transform into any other cell, so these iPS cells become heart cells again through the differentiation process. Heart cells are mixed with nutrients and growth materials to create bio-ink for a 3D bioprinter. The printer protects cells from degradation and prints the organ layer by layer with MRI measurements. The heart is placed in a bioreactor that mimics the human body's internal conditions. The cells self-organise and fuse into a network of living tissue and begin to beat together, and the framework dissolves, leaving a brand new, viable human heart, guided by MRI and printed from the patient's cells.
3D bioprinting of the musculoskeletal system: Bioprinting techniques have been used to create 3D skeletal muscle constructs using C2C12 myoblasts, resulting in high vitality and synchronized electro-pulse responses. Inkjet printers were used to differentiate primary muscle-derived stem cells into osteogenic and myogenic cell subpopulations based on BMP-2 growth patterns on fibrin-coated glass slides. Timelapse microscopy was used to show the development of multinucleated myotubes in bioprinted muscle-derived stem cells, and immunocytochemistry showed myosin heavy chain expression. These results showed how bioprinting can be used to create carefully regulated multilineage stem cell differentiation using structured immobilised growth factors.
3D bioprinting of neural tissue: 3D bioprinting technology has successfully developed neurons with voltage-gated potassium and sodium channels, maintaining basic cell phenotypes and functionality for over two weeks. Gu et al. used micro extrusion bioprinting to generate brain progenitor cells using a polysaccharide-based bio-ink. Neural stem cells can expand and differentiate into functional neurons and supporting neurons, resulting in spontaneous activity, synaptic contact, an increased calcium response, and GABA expression.
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In 2018, the WFIRM team published a study using rat heart cells to 3D-print function and contractile heart tissue. They assessed the effects of hormones like adrenaline and charcoal on implanted heart tissue, resulting in changes in heart rate and biological structures. In 2019, the research group and South African company Strait Access Technologies collaborated to create 3D-printed artificial heart valves that could replace leaking or damaged valves in real patients. These valves are made from body-compatible materials and are custom-made for each patient using MRI and CT imaging.
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Use of Artificial Intelligence in 3D Bioprinting
AI is rapidly transforming 3D bioprinting by creating biotissues using cells, growth factors, and biomaterials. By analyzing data and patterns, AI provides recommendations for optimal settings, ensuring biocompatible tissue that suits the patient's physiological composition. Machine learning can monitor the entire process and detect flaws like wrongly positioned cells, curved layers, and microstructure defects. Tissue repair and organ regeneration in regenerative medicine could revolutionize medical therapies. Stent-based therapies are a popular and adaptable regenerative medicine method. Stem cells' self-renewal and cell type differentiation make them ideal for treating many diseases and injuries. By leveraging the body's natural healing abilities, regenerative medicine is a medical paradigm shift. Regenerative medicine relies on stem cells, which can mend damaged tissues and organs like no other factor. Stem cells can self-renew and specialize into specific cell types, making them promising transplant candidates.