By Frances Matteck/editor-in-chief
More than 100,000 people in the U.S. wait on a list for organ transplants, the director of the Genetic Education Center told a NE Campus audience last week.
Sam Rhine brought the latest information on tissue engineering and stem cell research in a Feb. 11 presentation.
“We’ve tried everything we can think of to get more people to donate organs,” Rhine said. “It just doesn’t happen.”
REGENERATIVE MEDICINE
“So some people have taken an alternative approach.”
That alternative approach is regenerative medicine — inducing human tissues that are worn-out, damaged or missing.
Rhine used a bladder as an example and a recipe analogy to explain the creation process.
The required ingredients include epithelial and muscle cells from the patient’s existing bladder, a biodegradable scaffold and a laboratory.
The existing bladder receives a biopsy. Then the epithelial cells and muscle cells are separated from one another and expanded in vitro.
The cells are then transferred to the scaffold, which, in the case of the bladder, is shaped like a baggie. The scaffold is created in a beaker and molded in the shape of the organ needed.
The transfer process is known as seeding. During seeding, in the simplest terms possible, the epithelial cells are sprayed in a layer inside the bladder scaffold, and the muscle cells are sprayed in a layer outside the bladder scaffold.
As the cells develop, the scaffold disintegrates until only a bladder in a beaker remains.
Scientists remove the original bladder and insert the artificial one. Peripheral nerves, which are regenerative, from the urethra provide the bladder’s nerves. Its blood supply is provided by gluing the omentum drape, a vascular-rich flap in the abdomen, to the bladder.
In seven to eight weeks, a person with bladder cancer can get a brand new organ. Since the cells were taken from the patient’s original bladder, it decreases the percentage of organ rejection.
Rhine also gave the example of Lee Spievack, whose fingertip was cut off in a work-related injury.
Spievack’s brother researched regeneration at the University of Pittsburgh and sent him a powder composed of extracellular matrix, a mix of protein and connective tissue from a pig’s bladder.
The fingertip was regenerated after four weeks of applying the powder to the damaged portion.
REPRODUCTIVE CLONING
Rhine also discussed cloning — reproductive and therapeutic — and its medical applications.
Reproductive cloning creates a genetically identical copy of a particular individual born as a new baby.
Humans have 220 types of cells present by the eighth week of embryo development.
All of these cells develop during a process known as differentiation from either pluripotent or multipotent stem cells. Pluripotent cells have the potential to become any of the 220 somatic, or specialized, cells while multipotent only have the potential to become many of the somatic cells.
The cells follow one-way streets, Rhine said. They start out as stem cells and are directed to take certain streets by signals sent out by gene-produced proteins. When they reach their final form, it is known as terminal differentiation.
To date, scientists have cloned 17 species of animals from their somatic cells.
To clone, scientists remove the nucleus from an egg of a female of the species. Without the nucleus, the egg does not have genetic instructions.
The scientists then transfer the nucleus of a somatic cell into the egg, which provides it with the genetic instructions of the donor, and shock it to artificially activate it. On the sixth day, the egg has developed into an eight-cell embryo. It is transferred to a surrogate mother where the fetus develops normally and is, eventually, born.
Dolly, the famous sheep, is an example of reproductive cloning.
THERAPEUTIC CLONING
Therapeutic cloning involves the same process as reproductive cloning, except for the last step. Instead of the embryo’s being transferred to a surrogate mother, it is allowed to grow in vitro in a lab.
“A clone is a genetically identical copy of anything you choose,” Rhine said.
In therapeutic cloning, the clone stays in the petri dish.
Between the sixth and 10th days, scientists can remove the stem cells from the embryo and develop them in a lab until 10 billion embryonic stem cells become available.
With the appropriate sets of protein signals, scientists can create any somatic cell from these stem cells. This process is called in vitro differentiation.
The Human Embryo Project wants to define all 220 signals used to generate each somatic cell.
This process can be clinically applied in two different ways.
Cells can be created for people who do not have all of the somatic cells in their bodies. For example, sufferers of Type I diabetes do not produce the insulin their bodies need because they do not have the beta cells in their pancreas to create it.
With therapeutic cloning, those beta cells can be artificially created in a lab for the patient.
In the second application, scientists can take the nucleus from a patient who suffers from a genetic disease and insert it into the egg. They can then follow the cellular development of the disease in a lab environment and develop therapy. Examples of this include Lou Gehrig’s disease, Huntington’s disease and Down syndrome.
However, medical and bioethical issues arise with this avenue of research.
This type of research requires eggs donated by human females, a costly and painful process that, in the case of stem cell research, insurance companies will not cover. Successfully creating stem cells also takes time and money. After the cells are created, if any of the embryonic stem cells are transplanted into the host with the newly created somatic cells, the stem cells will develop into tumors.
The controversial bioethical issue is that the embryo is destroyed in the process.
ALTERNATIVES
A hundred people can look through a microscope at the embryo and see something different, Rhine said.
U.S. policy states no federal taxpayer dollars can be used to fund any research that involves the destruction of a human embryo.
In the face of these concerns and limitations, scientists have sought alternatives to obtaining pluripotent stem cells including altered nuclear transfer, biopsy of an eight-cell embryo and reprogramming, Rhine said.
Reprogramming is taking differentiation backward, Rhine said. In 2007, Shinya Yamanaka and James Thomson each led one of two teams of researchers that figured out how to revert adult skin cells to pluripotent cells. They are known as induced pluripotent stem cells (iPS).
This discovery bypasses all of the bioethical issues because there is no need to utilize the cells from an embryo.
“We’re supplanting the technical, tedious surgical stuff with a 30-second skin biopsy,” Rhine said.
For the first time in medical history, the cells for ALS, Huntington’s disease, Parkinson’s disease, Down syndrome, Becker muscular dystrophy and more are growing in petri dishes in a lab because of skin biopsies and iPS.
“You ain’t seen nothing yet,” Rhine said. “This has just started.”
