Case Study Building New Bones with Skin Cells

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					                                          Case Study
                     1.11                 Building New Bones with Skin Cells
                                          For the past thirty years, scientists have been developing new technologies and
                                          products to help replace damaged organs with parts grown in the laboratory.
                                          Biologists have recently been able to change human skin cells into bone and
                                          cartilage, the tissues that ears, noses, knees, and hips are made of. Recently,
                                          biologists have been studying certain types of cells that can be forced to
stem cell an unspecialized cell that      change their identities. Most of these biologists are focusing on stem cells—
may transform into a specialized cell     immature (unspecialized) cells that can, in theory, be transformed into any of
                                          the specialized cells of the body. Other researchers are working with certain
                                          mature (specialized) cells, such as skin cells, that they have been able to
DID YOU       KNOW     ?                  transform into other types of specialized cells, such as bone and cartilage cells.
Organ Donation in Canada
Canada’s organ-donation rate is
among the lowest of all the               Stem Cells
developed countries. More than            Every human being begins life as a single cell called a zygote—formed from
3000 Canadians are waiting for an         the combination of a sperm cell and an egg cell. This cell is not a bone cell, a
organ transplant. One organ donor
can donate numerous organs and            brain cell, or a skin cell. It is not specialized. However, in the cell’s nucleus,
tissues, including lungs, heart, liver,   there are 46 DNA molecules containing all of the instructions (genetic
kidneys, pancreas, bowel, eye tissue,     information) necessary to transform it into any of the specialized cells of the
skin, heart valves, bone, tendons,
veins, and ligaments. You can
                                          mature human body. The information in DNA is organized into sections
indicate your wish to become an           called genes, each gene coding for a particular characteristic of the cell. Why
organ donor on your health card or        does a cell like a zygote not use all of the information in its genes? Biologists
your driver’s licence. Discuss this       don’t yet have a satisfactory answer to this question, but experiments seem
decision with your family so your
wishes are known.
                                          to indicate that some of the chemical reactions controlling the genetic
                                          information are blocked. In other words, some of the genes are “turned off.”
                                          Therefore, in a zygote, the genes for producing the characteristics of a muscle
                                          cell or a bone cell are turned off, and only the genes for producing an
                                          unspecialized cell are turned on. These are stem cells. As the zygote divides by
                                          mitosis, it becomes a collection of unspecialized stem cells called an embryo.
                                             As an embryo continues to develop, various genes turn on in some of its
                                          cells, causing them to transform or differentiate into specialized cells.
                                          Specialized cells form tissues and organs, such as bone, heart, liver, and skin.
                                          However, not all cells specialize. Even in the adult human, stem cells may be
                                          found in bone marrow, skin, the spinal cord, and the brain. Stem-cell research
                                          has shown that under certain experimental conditions, embryonic and adult
                                          stem cells can be encouraged to become almost any kind of specialized cell.

                                          Embryonic Stem Cells and Cloning
                                          The use of tissues from human embryos raises many moral and ethical
                                          concerns, and while stem cells are found in adult tissues, they are difficult to
                                          isolate and collect because they make up only one out of every 10 000 cells.
                                          Using stem cells to produce tissues for transplantation may also cause
                                          medical complications. Just as the body rejects transplanted organs from
                                          donors, it can reject tissues grown from donated stem cells. Scientists have

48   Unit 1                                                                                                               NEL
                                                                                                       Case Study 1.11

discovered ways of avoiding this type of tissue and organ rejection through
a process called cloning. Cloning produces cells that are genetically identical
to the cells of the recipient, and thus are not rejected by the recipient’s
immune system. Nevertheless, cloning is a highly controversial process.
Two forms of cloning are therapeutic cloning and reproductive cloning.
In therapeutic cloning, the nucleus of a human egg cell is replaced with the        therapeutic cloning the
nucleus of a body cell (such as a skin cell) from the person who needs the          production of cloned embryos for
                                                                                    the purpose of obtaining stem cells
organ transplant. The egg cell is stimulated with a short pulse of electricity,
and it then develops into an embryo from which stem cells can be removed.           reproductive cloning the
These stem cells are genetically identical to those of the donor of the body-       production of fully formed cloned
cell nucleus and can be used to produce tissues that will not be rejected by        organisms
the donor’s immune system. Therapeutic cloning raises moral and ethical
dilemmas because human embryos are created and then destroyed in the
   Reproductive cloning begins like therapeutic cloning. An egg-cell nucleus is
replaced with a body-cell nucleus and stimulated to develop into an embryo.
The only difference is that in reproductive cloning the embryo is not used as a
                                                                                        epidermis            dermis
source of stem cells; instead, it is implanted in a uterus and allowed to develop
into an adult clone—an exact genetic copy of the donor. Dolly, the first cloned                          hair shaft
sheep, was produced by this method. Reproductive cloning also raises serious
moral and ethical dilemmas because it creates embryos artificially, and
because it introduces the possibility of creating humans for the sole purpose
of providing tissues and organs for other humans.

Skin Stem Cell Research
In 2001, Dr. Freda Miller and colleagues at the University of Montreal
Neurological Institute (MNI), discovered that skin contains stem cells that
may transform into a number of other cell types, including nerve cells, muscle
cells, and fat cells. Further research has shown that some types of stem cells in
                                                                                        fat tissue       hair root
skin may transform into bone and cartilage cells.
   Skin is the largest and most accessible organ in the body. Within the                hypodermis
dermis, the middle layer of human skin (Figure 1), are specialized cells called     Figure 1
fibroblasts. Recently, a number of researchers have been able to transform          Human skin
fibroblasts into bone and cartilage cells. From a small piece of skin no more
than a few cubic millimetres in volume, scientists have been able to produce        fibroblast an unspecialized skin cell
enough bone or cartilage to fill a cavity 200 to 300 times that size. And
because the original fibroblasts come directly from the patient, there is no
risk of rejection.
   In order to change fibroblasts into bone cells, scientists attach skin cells
to sticky netting made of protein, and surround the cells with phosphate
minerals like those normally found in bone. Within weeks, the fibroblasts act
just like bone cells and begin to produce the hard material that makes bones
rigid. When fibroblasts are packed tightly together and deprived of oxygen (a
condition normally found in cartilage tissue), they soon transform into
cartilage cells.

NEL                                                                                                  Cellular Biology 49
                                           Some of the promising applications of this research include the treatment of
                                        gum disease (also called periodontal disease) (Figure 2(a)) and osteoarthritis,
                                        a degenerative disease of the joints (Figure 2(b)). In advanced gum disease, the
                                        bone in the jaws deteriorates and teeth are lost. In osteoarthritis, a breakdown
                                        in the cartilage of hips, knees, and other joints causes thousands of patients
                                        every year to undergo painful hip- and knee-replacement surgery. Cartilage
                                        and bone replacement using skin fibroblasts may some day help cure these

Figure 2
(a) Advanced gum disease
(b) Osteoarthritis (in the knee on
    the right)                          (a)                                          (b)

        Case Study 1.11 Questions
  Understanding Concepts                                            (b) Injury to the cartilage in knee joints is common
   1. (a) What is a stem cell?                                          among athletes. A procedure called autologous
      (b) How may stem cells be used to help humans?                    chondrocyte transplantation (ACT) is sometimes
   2. Explain how genes determine whether a cell is a                   used to replace damaged knee cartilage. Briefly
      stem cell or a specialized cell.                                  describe the ACT procedure, and explain how the
                                                                        research described in this case study could help
   3. (a) What are fibroblasts?
                                                                        improve the process.
      (b) Why are fibroblasts of interest to transplantation
          biologists?                                                     GO
      (c) What medical advantages do fibroblasts have
          over stem cells in transplantation?                    6. Some scientists have been able to change stem cells
                                                                    obtained from fat tissue into cells that resemble nerve
     4. Describe the processes biologists use to change
                                                                    cells. Conduct research to determine how newly
        fibroblasts into bone and cartilage cells.
                                                                    transformed fat cells can function as nerve cells.
  Making Connections                                                 GO
  5. (a) What are some of the uses of bone and cartilage
         cells that have been made from fibroblasts?

50    Unit 1                                                                                                                  NEL