ARTIFICIAL ORGANS

ARTIFICIAL ORGANS (REGENERATIVE MEDICINE)

Scientists are calling regenerative medicine the "Holy Grail" of stem-cell research! The field of regenerative medicine works under the theory that organs can be grown outside the body. This science could revolutionize organ transplants.

Regenerative medicine is the process of creating living, functional tissues to repair or replace a tissue or an organ function lost due to damage, or congenital defects. This field holds the promise of regenerating damaged tissues and organs in the body by stimulating previously irreparable organs to heal themselves.

Regenerative medicine also empowers scientists to grow tissues and organs in the laboratory and safely implant them when the body cannot heal itself. Regenerative medicine has the potential to solve the problem of the shortage of organs available for donation compared to the number of patients that require life-saving organ transplantation, as well as solve the problem of organ transplant rejection, since the organ's cells will match that of the patient.

An artificial organ is a man-made device that is implanted or integrated into a human to replace a natural organ, for the purpose of restoring a specific function or a group of related functions so the patient may return to as normal a life as possible.

Let’s take a look at an artificial bladder.

On April 4, 2006, it was announced that a team of biologists at the Wake Forest University School of Medicine, led by Professor Anthony Atala, had created the world's first lab-grown organ, a bladder, and transplanted it into a human. Seven people between the ages four and 19, received transplants. The bladders were grown from a small sample of the patients' own bladder tissue, so there was no risk of transplant rejection. Usually, damaged urinary bladders are stitched back together using other tissue from the stomach or intestine. Patients with bladders made of intestinal tissues suffer unpleasant side-effects because intestinal tissues reabsorb chemicals that are meant to be eliminated through the urine.

Professor Atala and his team successfully extracted muscle and bladder cells from several patients’ bodies, cultivated these cells in petri dishes, and then layered the cells in three-dimensional molds that resembled the shape of bladders. Within a few weeks, the cells in the molds began functioning as regular bladders which were then implanted back into the patients’ bodies.

Artificial Organs
Pros	Cons
Allows the patient to possibly conquer a disease or illness	Possible presence of latent or hidden disease or illness in the base tissue (if the foreign body tissue used to reconstruct a particular organ or tissue is infected or hiding a disease)
Has the possibility of prolonging life and making the general quality of life better	Ethical issues
Can help burn victims regenerate skin
Organ transplant lists will become unnecessary
Solve the problem of organ transplant rejection because the organ’s cells with match that of the patient
Solve the problem of the shortage of organs available for donation compared to the number of patients that require life-saving organ transplantation

STEM CELLS

Stem cells have been a very controversial topic since they were discovered in the mid 1970s. The use of embryonic stem cells has caused many moral and practical dilemmas. Embryonic stem cell research requires the creation, usage, and destruction of human embryos. But today scientists are researching new ways to cure diseases without the use of embryonic stem cells.

Glossary

Stem cells: cells with the ability to divide for indefinite periods in culture and to give rise to specialized cells

Embryonic stem cells: undifferentiated cells derived from a 5-day preimplantation embryo that are capable of dividing without differentiating for a prolonged period in culture and are known to develop into cells and tissues of the three primary germ layers

Induced pluripotent stem cells (iPSC): a pluripotent stem cells artificially derived from a non-pluripotent cell, typically a somatic cell, by inducing a forced expression of specific genes which preprograms the cell to enter and embryonic stem cell-like state

Adult stem cells (somatic stem cells): a relatively rare undifferentiated cell found in many organs and differentiated tissues with a limited capacity for both self renewal (in the laboratory) and differentiation

Pluripotency: the capacity to morph into any tissue in the body

Preimplantation: embryo has not yet implanted in the wall of the uterus

Some depth

Stem cells have the potential to develop into many different cell types in the body during early life and growth. They may for tissues that serve as a sort of internal repair system, dividing essentially without limit to replenish other cells. Each new stem cell, when it’s dividing, has the potential to either remain and stem cell or become another type of cell with a more specialized function. Two fundamental properties of stem cells are that they are capable of renewing themselves through cell division, sometimes after long periods of inactivity, and they can be induced to become tissue-specific or organ-specific cells with specialized functions, under certain experimental conditions.

iPSCs demonstrate important characteristics of pluripotent stem cells. They include the expression of stem cell markers, the formation of tumors contain cells from all three germ layers, and the ability to contribute to many different tissues when injected.

Somatic cells vs. embryonic stem cells: Both types of stem cells have potential for cell-based regenerative therapies. However, there are some major differences. Embryonic stems cells are pluripotent. Somatic stem cells are thought to be more limited to differentiating into different cell types of their tissue of origin. Embryonic stems cells can be grown relatively easily in culture while somatic stem cells are rare. Embryonic stem cells have a higher chance of rejection than somatic stem cells because somatic stem cells contain the host’s DNA so they are perfect matches as opposed to an embryo.

Medical experiments

Parkinson’s disease: Researches have created embryonic stem cells to become the types of cells damaged by this neurodegenerative disease and grafted them into the appropriate brain area of mice (who were injected with a deficit similar to Parkinson’s disease). Results showed that the neurons integrated themselves into the mice’s tissue and made proper connections. However, some cells were cancerous because they had a high potential to divide.

Spinal cord injury: Researches grafted human neural stem cells into mice with spinal cord injuries. The results produced appropriately differentiated cells and helped the mice recover motor function. But this stem cell therapy will take years before a clinical therapy is available for humans.

Experimental heart repair: Stem cells are currently used in a human clinical trial to repair the heart muscle that was damaged or destroyed during heart attacks. These stem cells come from bone marrow and circulating blood. Data suggests that these cells may help make moderate repairs, but there is no significant date to make a conclusion yet.

Differentiation

Scientists can harvest and maintain stem cells and they can cause stem cells to differentiate in to many different lineages, but some types of differentiation are hard to control. For example, the proper differentiation and growth of neurons are still difficult to perform, whereas the differentiation to muscle is easier. Scientists use growth additives to encourage differentiation. For example sonic hedgehog and retinoic acid are used to tell cells what to do. Also, activin is similar in function to sonic hedgehog. Hormonal environments also affect the path a stem cell can take in its differentiation.

EMBRYOLOGY

Embryology, what exactly is embryology? It is the science concerning the development of an embryo form the fertilization of the ovum to the fetus stage. Fertilization occurs in a series of steps: contact between the sperm and egg, entry of sperm into the egg, fusion of egg and sperm nuclei, and activation of development .During fertilization, a sperm must fuse with and penetrate the female egg for a successful fertilization. Fusing is the easy part, but penetrating through the egg’s hard protective shell is a problem for sperm. Thus, sperm go through a process called the acrosome reaction. An acrosome reaction is the reaction that occurs in the acrosome of the sperm as it approaches the egg. The acrosome is a cap-like structure over the frontal (anterior) half of the sperm’s head. As the sperm approaches the zona pellucid (glycoprotein membrane) of the egg, which initiates the acrosome reaction, the memebrane surrounding the acrosome fuses with the plasma membrane of the sperm. The contents (surface antigens and enzymes to break through egg’s hard shell) are exposed allowing fertilization to occur. The cortical reaction occurs directly after the acrosomal reaction. It happens when a sperm cell fuses with the egg’s plasma membrane which alters the zona pellucid preventing other sperm from binding and entering the egg. It is the exocytosis of the egg’s cortical granules (secretory vesicles below the plasma membrane). When the sperm is in contact with the egg’s plasma membrane, calcium is released from storage sites in the egg triggering the fusion of cortical granule membranes with the egg plasma membrane. The wave of calcium surrounds the egg and a wave of cortical granule fusion results.

Cleavage is the first step in development for all multicellular organisms. It converts a single-celled zygote into a multicelled embryo via mitosis. It is the division of cells in the early embryo. The blastula is produced by mitosis of the zygote. A blastula is a ball of cells surrounding the blastocoel (fluid-filled cavity). As a result of rapidly dividing cells, their size decreases. However, it increases their surface area to volume ratio to increase allowing more efficient oxygen exchange between cells and their environment. The blastula receives RNA and information carrying molecules to start the differentiation of cells and early development.

Grastrulation occurs next. It is a series of cell migration to positions where they will form three primary cell layers: ectoderm (outer layer), endoderm (inner layer), and mesoderm (middle layer). This single-layered blastula is reorganized into a gastrula. The ectoderm forms tissues such as skin, hair, sweat glands, and epithelium. It also develops the brain and nervous system. The mesoderm forms structures associated with body movement and support. Mesoderm structures include muscles, cartilage, bone, and blood. It also forms kidneys and reproductive organs. Reproductive organs are also developed by the archenteron. The archenteron is the primitive gut that forms during gastrulation in the developing blastula. Lastly, the endoderm forms tissues and organs that aid in digestion and respiration. Endocrine structures such as the thyroid and parathyroid glands are formed by the endoderm. The liver, pancreas, and gall bladder are also developed by the endoderm.

Organogenesis is summed up by its name, the creation of organs. It is the process by which the ectoderm, endoderm, and mesoderm develop into internal organs. For humans, this process usually occurs between the third and eighth week in utero. The germ layers in organogenesis differ by three processes. These three processes are folds, splits, and condensation.  

Let’s take a closer look at fertilization in sea urchins.

Fertilization is external. Most sea urchins have their eggs free floating in the sea, but others keep them on their spines for protection. To prevent the sperm and egg from being washed away they have evolved mechanisms to bring the gametes together. When a sperm cell encounters an egg of the same species, components of the jelly coat bind to specific egg receptors in the plasma membrane. This triggers the release of calcium that facilitates fertilization.

In the sea urchin, early cell divisions are rapid. The proteins that are synthesized during cleavage utilize mRNA found in the cytoplasm provided by the mother. The first three cell divisions bisect the embryo equally; the fourth cleavage divides the cells in the top half equally, but those in the bottom half unequally. The cells continue to divide until the form the blastula.

A sea urchin embryo has ten cycles of cell division to make a single epithelial layer enveloping a blasteocoel. The embryo then begins grastrulation, a multipart process which dramatically rearranges and invaginizes cells to produce three germ layers.

The fertilized egg develops into a free-swimming blastula embryo in as little as twelve hours! The simple blastula transforms into a cone-shaped echinopluteus larva which has elongated arms, nutrients, a cilia to capture food particles. It may take several months for the larva to be fully developed. The larva sinks to the bottom of the sea after development is completed and metamorphoses into an adult in as little as one hour.