What Is Regenerative Medicine?
Regenerative medicine is a relatively new term for a transformative branch of medicine that has been evolving for quite some time. Even as far back as the 1800s, scientists understood that cells are the basic building blocks of the body, and that some cells can generate other cells. By the late 1900s, scientists had found replicating cells in every tissue of the body. These cells are now broadly known as “stem cells.”
Regenerative medicine is a promising field that aims to restore the function and structure of damaged organs in both acute and chronic diseases settings, possibly providing a cure for previously incurable diseases and injuries, including diabetes, rheumatoid arthritis, heart disease, autoimmune disorders — the list of possibilities is growing at an astounding rate.
Strategies in Regenerative Medicine
The field of regenerative medicine continues to evolve rapidly. In addition to medical applications, non-therapeutic applications include using tissues as biosensors to detect chemical or biological threat agents and tissue chips to test the toxicity of an experimental medication. Current medical applications in regenerative medicine include the following:
Tissue Engineering and Biomaterials
This strategy involves implanting biologically compatible tissue scaffolds at the site where the new tissue is to be regenerated. The scaffold, consequently, attracts cells, which regenerates the tissue. If the tissue scaffold is in the geometric shape of the original tissue, the resulting tissue will form this desired shape.
Biomaterials stimulate tissue regeneration by mimicking the tissue framework, called the extracellular matrix, on which the body of the tissue is organized. For instance, with this approach, 3D polymer scaffolds are used in cartilage injuries and venous ulcers to provide an expansion of cartilage cells (chondrocytes) and specific cells that promote tissue thickening (fibroblasts) respectively.
Moreover, these biomaterials may be impregnated with growth factors to enhance tissue repair and regeneration. In bone repair and formation, biomaterials may be incorporated with bone morphogenic proteins 2 and 7, and for wound healing, the biomaterial may be impregnated with platelet-derived growth factor (PDGF) to stimulate and sustain the growth of the respective cells.
Cellular therapies employ the potency of the stem cells in regenerating tissues — this involves harvesting stem cells and injecting them into the site of the damaged tissue or organ. Under the right conditions, the stem cells renew and reconstruct the tissue.
Harvested stem cells come from various organs and tissues, such as blood, bone marrow, dental pulp, skeletal muscles, and cord blood. It is not clear how similar stem cells derived from a non-bone marrow source are to those from bone marrow stroma. These cells may be harvested from the same person (autologous) or from someone else (allogeneic) when regeneration is needed. Orthopedic specialists are finding the use of regenerative medicine very promising to support injuries and degenerative diseases. Other examples of cellular therapies involves the injection of fibroblasts into the skin to reduce wrinkling, as well as use of skin cells, or keratinocytes, for skin repair in patients with severe burn wounds.
Medical Devices and Artificial Organs
In an attempt to bypass obstacles associated with organ transplants, such as immune complications and low donor supply, medical devices and artificial organs have been developed to provide temporary or permanent restoration of function of the diseased or injured organ. For instance, ventricular assist devices (VAD) have found promising use in patients with severe heart failure and ventricular dysfunction both as a long-term cardiac support and as a bridge to cardiac transplant.
Also, bioartificial liver tissue has been developed to support liver function in patients with severe hepatic insufficiency who require a liver transplant. Other engineered tissue includes pancreas, bladder, lung, skin, and bone — these have been created to provide the required support in patients with diseases affecting each organ.
The Future of Regenerative Medicine
The overall aim is to bring advanced solutions that aid and supplement the natural healing mechanisms of the body. One such solution is recapitulating tissue and organ structures by the decellularization and recellularization of organs before transplantation.
Decellularization of organs involves several processes to remove immunogenic cells and molecules from the organ, sparing the framework substance of the tissue, or the extracellular matrix. Decellularized tissue (without recellularization) has been used to repair large tissue damage. A variation of the method is in use for kidney dialysis where blood vessels are processed and decellularized before placing them in patients. While excellent progress has been made in regenerative medicine through decellularization, it is necessary that protocols be further developed to optimize the process.
Another approach in development is altering the host environment and immune system to promote tissue repair. This involves the administration of specific cells, which can indirectly trigger natural therapeutic responses, such as growth factors, without injecting the cells directly into the damaged tissue. An example is injecting cord blood stem cells into a patient with acute stroke to promote migration of neuroblasts to the injury site for the repair and regeneration of brain tissue.
How Do Stem Cells Work, and What Are Their Capabilities?
It’s important to understand that stem cells are only one, a single component that catalyzes many larger cellular components — a plethora of nucleated cells. When stem cells are put into the body, they are innately attracted to damaged cells. This is because damaged cells in your body give off a chemical signal in their vicinity, known as the paracrine space. Stem cells will attach themselves to a nearby blood vessel, where they can function as pericytes. Pericytes are cells that give nutritional support to the damaged cells, with the goal of regenerating them back to their normal, functioning condition.
Perhaps one of the most important aspects of the stem cell is its natural anti-inflammatory effect. When a tissue injury is inflicted, a spectrum of biochemical reactions erupts at the injured site — whether that’s a joint or soft tissue. Within that spectrum of biochemical reactions is the production of tumor necrosis factor alpha (TNF alpha) and interferon gamma, as well as interleukins 1, 2, and 12. These are known as type 1 helper (Th1) cells, and they’re necessary for the inflammatory process to take place.
Anti-inflammatory Proteins and Immunomodulatory Cytokines
Mesenchymal stem cells also deliver a plethora of anti-inflammatory proteins and immunomodulatory cytokines, including: prostaglandin E2 (PGE2, also known as dinoprostone), which relaxes smooth muscle, tissue-growth factor beta 2 (TGFB2), hepatocyte growth factor (HGF), nitric oxide, interleukins 4, 6, and 10, and many more. They also deliver an essential protein called Interleukin-1 Receptor Antagonist (also known as IL-1RA) — these function as type 2 helper (Th2) cells that aid significantly in balancing the inflammatory process. This is important, as nearly all autoimmune disorders are T1 weighted, meaning they’re pro-inflammatory disorders. Umbilical cord-derived stem cells have the ability to rapidly modulate these T1 and T2 helper cells so that they discontinue their attack on the body. Remember, IL-1 is pro-inflammatory; thus, IL-1RA inhibits the expression of IL-1, or the inflammatory process. This makes IL-1RA an incredibly efficient natural inhibitor of inflammation. Additionally, it inhibits tumor necrosis factor alpha, which is indicated in many autoimmune diseases.
Anti-Apoptotic and Antimicrobial Effects
Another major function of stem cells is their anti-apoptotic effect. Apoptosis is defined as programmed cell death, and as cells get old and cease to function properly (called senescence cells), eventually they collapse their cell walls and expel the DNA stored. Stem cells have the remarkable capacity to give trophic support to the senescence cell (the aged cell that is no longer functioning correctly) and restore it to a functioning state. And, when one cell functions in a healthy state, it aids in keeping the cells around it functioning correctly.
Furthermore, a recent new and exciting use of stem cells is for their antimicrobial effects. Stem cells are programmed with innate immune defense against microbial infections, which comes from a handful of polypeptides. There are also studies being done against acute, chronic, and even significant systemic infections, to which there has reportedly been an excellent response.
Regenerative medicine and cell-based therapies are breaking boundaries and improving the lives of people suffering from damaged tissues resulting from injury, disease, or age. The rapid expansion of scientific knowledge creates new frontiers for continuing the advancement in this field of medicine. As research moves forward, the opportunities for more extensive patient treatments will provide advanced solutions to the treatment of previously fatal and untreatable diseases.
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