Joshua Hare, MD, FAHA, Program Co-Chair for the AHA’s Basic Cardiovascular Sciences (BCVS) 2011 Scientific Sessions; Roberto Bolli, MD, FAHA from the University of Louisville; and Piero Anversa, MD, FAHA from Brigham and Women’s Hospital discuss stem cell translation research at the BCVS 2011 Scientific Sessions, held at the Ritz-Carlton Hotel in New Orleans, Louisiana from July 18-21, 2011.
In this video I will lay out my thinking as to why stem cell therapy is the next boom; it will in fact, change the world. What do you think?
www.cellmedicine.com
Stem Cell Types And Their Use In Internal Stem Cell Therapeutics
Introduction
This short paper will focus on stem cell therapeutics where stem cells are injected into the patient, as opposed to other stem cell-based therapeutics where the cells, or their products (such as proteins released from the stem cell) are applied topically to the patient. As injectables, stem cells have been demonstrated to be the most important therapeutic for many diseases and conditions because of three important characteristics that they possess. First, stem cells are unspecialized cells that can replenish their numbers for long periods through cell division. Second, after receiving certain chemical signals, they can differentiate, or transform into specialized cells with specific functions, such as a heart cell or nerve cell. Third, and research and clinical practice suggests this aspect of stem cells may be their most important, stem cells have been shown to release and respond to a number of tissue regenerating proteins, including growth factors and cytokines. These three important characteristics distinguish stem cells from other cells in the body that do not possess these characteristics and therefore cannot be used in cellular therapeutics nearly as effectively as can the stem cells.
2. Classification Of Stem Cell Type
Stem cells are often classified by the extent to which they can differentiate into different mature cell types, (but this classification does not specify what the cell types are able to release and respond to as signaling molecules):
A. Totipotent stem cells can differentiate into any cell type in the adult body, and into the placenta to nourishe the embryo. A fertilized egg is a type of Totipotent stem cell. Cells produced in the first few divisions of the fertilized egg are also Totipotent.
B. Pluripotent stem cells are descendants of the Totipotent stem cells of the embryo. These cells, which develop about four days after fertilization, can differentiate into any cell type, except for Totipotent stem cells and the cells of the placenta.
C. Multipotent stem cells are descendants of Pluripotent stem cells and antecedents of specialized cells in particular tissues. For example, hematopoietic stem cells, found primarily in the bone marrow, give rise to all of the cells found in the blood, including red blood cells, white blood cells, and platelets. Another example are the neural stem cells that can differentiate into nerve cells and neural support cells called Glia.
D. Progenitor cells (or Unipotent stem cells) can produce only one cell type. As an example, Erythroid Progenitor cells differentiate into only red blood cells. At the end of the long chain of cell divisions are “terminally differentiated” cells, such as a liver cell or lung cell, that are permanently committed to specific functions. These cells stay committed to their functions for the life of the organism or until a tumor develops. In the case of a tumor, the cells differentiate, or return to a less mature state. Research continues on both adult and embryonic stem cells to determine the characteristics and potential of both to cure disease.
Stem cells is a term used to describe all cells that can give rise to cells of multiple tissue types. However, there are different types of stems cells. Totipotent cells, like the cells of a fertilized egg in the first few days after fertilization, can give rise to a fully functional organism. During normal development, the Totipotent cells become more specialized and are considered Pluripotent, meaning that they can give rise to every cell type in the body, but will not give rise to the placenta or supporting tissues necessary for fetal development. Because their potential is not total, they are not Totipotent and they are not embryos. Pluripotent stem cells undergo further specialization into stem cells committed to generating cells that are specialized for a particular function. Multipotent cells can give rise to the cell types found in the tissue from which they were derived, such as blood stem cells that give rise only to red blood cells, white blood cells and platelets, or skin stem cells that give rise only to the various types of skin cells.
3. Stem Cells Used For Cell Therapy
Stem cell therapy can be defined as a group of new techniques and technologies that rely on replacing diseased or dysfunctional cells with healthy, functioning cells, or replacing the molecules that the transplanted stem cells normally release into the area of tissue that is the recipient of the therapy. These new techniques are being applied to a wide range of human diseases, including many types of cancer, neurological diseases such as Parkinson’s, Lou Gehrig’s disease, multiple schlerosis, spinal cord injuries, and diabetes. Further, replacing dysfunctional cells in the retina with new ones may someday cure even presently incurable neurodegenerative eye diseases such as glaucoma and macular degeneration. To understand how cell therapy works, we need to understand the role of cells in the body.
4. The function of cells
Cells are the basic building blocks of the human body. These tiny structures compose the skin, muscles, brain, bones and all of the internal organs. They also hold many of the keys to how our bodies function. Cells serve both a structural and a functional role in the body, performing an almost endless variety of actions to sustain the body’s tissues and organs underlying our mentation and our actions.
There are thousands of different specialized cell types in the adult body. All of these cells perform very specific functions for the tissue or organ in which they reside. Specialized cells in the heart muscle intrinsically “beat” rhythmically through the internal propagation of electrical signals are an example, while the cells of the pancreas produce and secrete insulin to help the body convert food to energy are another example. These two mature cells types have been differentiated, or dedicated, to performing their special tasks. Until recently, scientific evidence suggested that under normal conditions, once a cell has become specialized, it cannot be changed into a different type of cell.
Like the body itself, cells have a finite life span and will eventually die. Most of the cells in the body divide and duplicate throughout life, but some cells either don’t replenish themselves, or do so in such small numbers that they cannot replace themselves fast enough when faced with disease or injury where a large number of cells are destroyed at one instance.
5. How stem cell therapy works
While cells are indispensable in performing vital functions for the body, they can also exist outside the body using special scientific laboratory techniques. The cells can live and divide outside the body in “cultures,” utilizing special solutions in test tubes or Petrie dishes. This ability of certain cell types to live isolated from other cells under controlled conditions has allowed scientists to study them independently of the organ or system in which they are normally a part. Through the isolation and targeted manipulation of cells, biotech companies are finding ways to identify young, regenerating cells that can be used to replace damaged or dead cells in diseased or damaged organs. This therapy is similar to the process of organ transplant, however in stem cell therapy the treatment consists of the transplantation of cells rather than organs. The cells that have shown by far the most promise of supplying diseased and damaged organs with healthy new ones are called stem cells.
A key question in stem cell research and therapy is, do adult stem cells have the same therapeutic capability as embryonic stem cells? For many years, scientists have conducted studies to determine whether the stem cells in adult tissue have the same developmental capability as embryonic stem cells. The answer is yes and no, depending on the exact capability that is required for the therapeutic regimen. If we think of using stem cells for the conversion of the stem cell into a new, differentiated cell type (e.g. turning the stem cell into a heart cell) then the general consensus is that adult stem cells seem to be less versatile. However, if we think of stem cells as a means for repairing tissue through the release of “healing-molecules” into the damaged tissue, then adult stem cells may prove to be more effective then embryonic stem cells. Thus therapies for different types of conditions may require one or the other type of stem cell, or may require both the embryonic and the adult stem cell for proper reparation of the tissue.
6 The current use of cell therapies
Even though most of the work done in this field has been experimental in the USA, most scientists here find cell therapy so promising that they believe in a short time stem cell therapy will be routine. And while many uses of stem cell therapy may be years away, there are a few forms of this technique that have already been in use for years. Bone marrow transplants are an example of cell therapy in which the stem cells in a donor’s marrow are used to replace the blood cells of the victims of leukemia and other cancers. Cell therapy is also being used in experiments to graft new skin cells to treat serious burn victims and diabetic ulcer wounds, and to grow new corneas for the sight-impaired. In all of these uses, the goal is for the healthy cells to become integrated into the body, acting as new cells that begin to function like the patient’s own cells and/or releasing growth factors and proteins into the damaged tissue to begin the regeneration process.
Thus far results of such experiments have exceeded expectations. In a recent advance, pancreatic cells grown from stem cells were implanted into the body of a diabetic and began to produce and release insulin. Results of the aforementioned therapies have caused great optimism in the scientific and medical communities. However, there are a number of scientific challenges that must be overcome before we can harness the complete power of stem cells for therapeutic use.
7. Current challenges of stem cell therapies
One of the first challenges to be overcome before stem cell therapies become commonplace is the difficulty of identifying stem cells in tissue cultures, which contain numerous types of confounding cells. While scientists are discovering new cell types almost every day, estimates are that thousands of human cell types exist. The process of identifying any desired type of stem cell will involve painstaking research. A second challenge, once stem cells are identified and isolated, the right biochemical solution must be developed to cause these progenitor cells to differentiate into the desired cell type, or to release their “healing-molecules.” This too will require a great deal of experimentation.
A third challenge arises when the cells are implanted into a person. The cells must be integrated into the patient’s own tissues and organs and function in concert with the body’s natural cells. Cardiac cells that beat in a cell culture, for example, may not beat in rhythm with a patient’s own heart cells. And neural stem cells injected into a damaged brain must become “wired into” the brain’s intricate network of cells and their connections in order to work properly.
Another challenge is the common phenomenon of tissue rejection. Similar to organ transplants, the body’s immune cells will recognize transplanted cells as “foreign,” setting off an immune reaction that could cause the transplant to fail and possibly endanger the patient. Yet another concern is the possible risk of inducing cancer. Cancers result when cells lose their internal stop mechanisms and keep dividing when further proliferation is no longer desirable. Researchers must find a delicate balance between fostering the growth of new cells to replenish damaged tissues , while preventing them to overgrow and become cancerous. Recent studies suggest that these obstacles can be overcome and the power of stem cells can be fully harnessed.
Beyond the scientific and medical challenges, there are also ethical, social, financial and political issues affecting this new industry. One of the hardest issues for this industry to overcome is that patients are generally offered stem cell therapy after all other treatments have been exhausted, therefore limiting the chance for success. As is natural in the business world, success of stem cell therapy poses a serious financial threat to many other conventional treatments, and there are, therefore, powerful forces that using their power to minimize this industry’s successes and magnify its failures.
8. Some aspects of future stem cell therapy
Despite the many challenges facing scientists, most believe that stem cell therapy will revolutionize medicine. With the use of cell therapies, we may soon have dramatic cures for cancer, Parkinson’s, diabetes, kidney disease, multiple sclerosis, muscular degeneration, glaucoma, and many other diseases. Stem cell therapies have also shown great promise in helping to repair catastrophic wounds from burn and diabetic ulcers, spinal injuries, sickle cell anemia, and helping victims of paralysis regain movement. Stem cell therapies also provide the possibility that the human life span could be greatly extended due to the replenishment of tissues in aging organs. Perhaps one day we’ll be able to grow our own organs for transplantation from our own stem cells, eliminating the danger of organ rejection. While we will undoubtedly advance stem cell therapy one day to a full realization of its potential, in practice today as we speak, many humans around the world are experiencing better lives because of stem cell therapeutics in one form or another.
Dr. Maguire has spent over 20 years in research and development as a professor of neuroscience and ophthalmology at the UCSD School of Medicine where he was awarded an NIH Fogarty Fellowship and ran an NIH- and NSF-grant supported research laboratory. Dr. Maguire holds numerous patents for drugs and devices, has over 100 publications in the areas of neuroscience, ophthalmology, cancer, and pharmaceuticals, is a founder and director of two biotechnology companies and two non-profit life science organizations, and has led the implementation of several large BD contracts between biotech and big pharma companies. He serves on the Scientific Advisory Board of several health care companies and routinely lectures around the world on health care and pharmaceutical related issues. He is Co-Founder and CEO of A & G Skin Solutions,Inc. www.agskinsolutions.com and CEO of Molecular Sciences, Inc., a pharmaceutical regulatory and managment company. He is also President of the San Diego Neuroscience Group at the Scripps Research Institute in La Jolla, CA. http://www.scripps.edu/services/sdneuro/ Email:gregmaguire5@gmail.com
Amid the blast walls and cacophony of Baghdad, patients at a local clinic are receiving potentially groundbreaking stem cell therapy, treatments that remain illegal and unproven in many countries.
Dr. Abdul Majeed Alwan Hammadi is conducting the treatments for free, mostly on young Iraqis. He is a clinical hematologist who works in the Bone Marrow Transplant Center, part of Baghdad’s Medical City complex of hospitals on the eastern banks of the Tigris River.
Hammadi says he started therapies in 2008 and has so far treated 34 patients, the majority for multiple sclerosis.
Bagdad Iraq
Hammadi, who graduated from a medical college in Baghdad, claims no side effects have been reported in his patients. He said he is in the process of collecting his data for publication, while also seeking official license for the therapies from Iraq’s Ministry of Health, which funds the center.
One of Hammadi’s patients and proponents of the therapy is the Rev. Andrew White, a British priest who runs St. George Church on Baghdad’s Haifa Street.
White was diagnosed with multiple sclerosis in 1998 and said his vision, speech and motor skills were steadily degenerating until he began Hammadi’s therapy in January.
White helped Hammadi establish the bone marrow center in Baghdad in 2001, bringing the doctor and his staff to England for training in marrow transplant techniques.
White said his slurred speech and other MS symptoms improved since starting the three-hour therapy sessions, which involves Hammadi extracting adult stem cells from White’s blood and then injecting them into his spinal cord.
It is unknown why MS causes the body’s immune system to attack the protective coating around nerve fibers, known as myelin, which results in nerve damage and loss of motor functions. The condition’s severity varies, with some people improving on their own while others continue to degenerate.
The potential benefits of stem cell therapy for MS are still being analyzed and researched in the Western world, but White said he accepted Hammadi’s offer for treatment because his symptoms were so severe and he trusted his friend.
“When there’s no other treatment, you kind of just go with it,” White said. “At least there’s a chance.”
White said the therapy itself “can be a bit painful” since it involves a spinal cord puncture, but there has been a “massive difference” in his condition.
“It’s very rare for me to actually feel ill now,” he said. “My balance is still quite bad and my vision is not perfect, but I do not feel ill.”
MS doctors and researchers believe stem cell therapies could pose benefits for those suffering from the disease, but the research is still unproven at this point, according to Dr. Patricia O’Looney, vice president of biomedical research for the National Multiple Sclerosis Society’s research and clinical program department.
One theory is that a person’s adult stem cells can work to rebuild the myelin around nerve fibers that is eaten away by a person’s immune system under MS, halting any further damage.
Hammadi said he is the only doctor in Iraq performing such therapies, but that there are similar operations being performed in Iran and Lebanon.
At this point, the therapies aren’t proven, and any side effects from the treatments are unknown, O’Looney said. “We’re seeing a wide range of results [at the stem cell clinics], which tells us there might be a hint of benefit, but what we need to do of course is a larger study to really understand if stem cell therapy is beneficial,” she said, adding that because stem cell research is only about 10 years old, enough isn’t known yet about the cells. “We do discourage anyone with MS from going to these so-called stem cell clinics,” O’Looney said.
But for patients like White and others suffering from the disease, waiting for the research to come through can be too much to bear.
Part of some patients’ sense of urgency comes from the disease’s unpredictability. Sometimes the disease goes into remission on its own; sometimes a patient is in a wheelchair within 10 years of being diagnosed.
As a result, MS sufferers have sought out a variety of cures over the years, O’Looney said. “If you flash back 25 years ago before [current MS therapies], people were using snake venom or bee stings.”
Stem cell clinics based on untested science can also give false hope to those with MS, O’Looney said, and positive results like White’s could be due to a number of factors, from pre-existing therapy regimens to the body’s immune system correcting itself on its own. “Just because someone switched from tomato juice to orange juice in the morning and feels better doesn’t mean it’s the orange juice,” she said. “The body does have the capability to repair itself.”
But for some patients like White, hope is all there is when dealing with MS. No matter where the treatment takes place.
“In the midst of the war zone, I get such high-tech treatment,” he said. “I can go to Baghdad and get it.”
Blood can be collected from the umbilical cord of a newborn baby shortly after birth. This blood is rich in blood stem cells that can be used to generate red blood cells and cells of the immune system. Cord Blood stem cells can be used to treat a range of blood disorders and immune system conditions such as leukaemia, anaemia and autoimmune diseases. Once collected, cord blood can be stored in a cord blood bank and would be available for use by the donor and compatible siblings.
Alternatively, the cord blood may be donated to a general cord blood bank for use by other tissue matched individuals in need of a transplant. It is hoped that over time a store of cord blood stem cells from people of different tissue types may be established. Someone requiring a transplant would be treated with stem cells from the sample most closely matching their own tissue type, thus minimising complications associated with immune rejection.
Cord blood stem cells may also be useful for treatment of diseases other than blood disorders. Preliminary research reports suggest that cord blood stem cells may have a greater ability to differentiate into different cell types than was previously thought possible. Using animal model, several research groups have used human cord blood stem cells to treat heart attacks and repair injured blood vessels. However, this research is at a very early stage. Scientists are presently unsure whether the cord blood stem cells are transformed into heart muscle or blood vessels, or if they secrete growth factors, that trigger repair. If further studies and clinical trials prove successful, cord blood stem cells may provide a new treatment for cardiovascular disease with fewer side effects than current drug based and surgical treatments.
The use of cord blood stem cells in cell-based therapies for blood and immune diseases, and for other potential applications, would be welcomed by the majority of the community. Although cord blood stem cells are less versatile than Embryonic Stem cells, their use in research is less controversial as it does not involve the destruction of embryos. Their potential use for cell-based therapies is also attractive as it would be possible to use a patient’s own cord blood stem cells to generate tissue for transplantation, thus avoiding problems with immune rejection.
Controversy has arisen over the practice of genetically selecting embryos created during infertility treatment, for the purpose of using the donor baby’s cord blood to treat an ill sibling. In this procedure, genetic testing is performed to ensure that the embryo will provide cord blood devoid of the genetic defect afflicting the sibling, but which matches the sibling’s genetic make up. The donor baby in this case is sometimes referred to as a ‘savior sibling’.
The first ‘saviour sibling’ to be born in Australia was reported in March 2004. A Tasmanian couple used this technology to have a second child who was free of a genetic condition, Hyper IgM Syndrome. Cord blood from this child could be used to treat the affected sibling. As a result of this selection process carried out Sydney IVF Clinic, the woman started her pregnancy knowing that her baby was free of Hyper IgM Syndrome and would be a potential tissue donor for her existing son.
The creation of ‘saviour siblings’ has evoked a quite heated debate in both the medical and general community. Some are vehemently opposed to this application, considering this the first step in ‘designer babies’. Others consider it highly unethical not to use this technology to help the sick sibling. The overarching issue to be considered is the well being of the ‘savior sibling’, and to ask the question whether they will be disadvantaged by the procedure. These are questions to be considered by both the biomedical and general community when considering applications of any new technology.
When people think of the word ‘cloning’ they are often hit with frightening images of duplicate human beings being created in somewhat of a mad scientist style experiment. In fact, many members of the public were outraged when Dolly the sheep resulted from a cloning experiment in Scotland. Therapeutic cloning, however, is entirely different and does not involve the creation of a perfectly copied human being. It is reproductive cloning that results in a copy of a specific human being. In therapeutic cloning, no sperm fertilisation is involved nor is there implantation into the uterus to create a child.
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Therapeutic cloning is another phrase for a procedure known as somatic cell nuclear transfer (SCNT). In this procedure, a researcher extracts the nucleus from an egg. The nucleus holds the genetic material for a human or laboratory animal. Scientists then take a somatic cell, which is any body cell other than an egg or sperm, and also extract the nucleus from this cell. In practical human applications, the somatic cell would be taken from a patient who requires a stem cell transplant to treat a health condition or disease.
The nucleus that is extracted from the somatic cell in the patient is then inserted into the egg, which had its nucleus previously removed. In a very basic sense, it’s a procedure of substitution. The egg now contains the patient’s genetic material, or instructions. It is stimulated to divide and shortly thereafter forms a cluster of cells known as a blastocyst. This blastocyst has both an outer and inner layer of cells and it is the inner layer, called the inner cell mass that is rich in stem cells. The cells in the inner cell mass are isolated and then utilised to create embryonic stem cell lines, which are infused into the patient where they are ideally integrated into the tissues, imparting structure and function as needed.
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A major benefit of therapeutic cloning is that the cells removed are pluripotent.
Pluripotent cells can give rise to all cells in the body with the exception of the embryo. This means that pluripotent cells can potentially treat diseases in any body organ or tissue by replacing damaged and dysfunctional cells. Another distinct advantage to this type of therapy is that the risk of immunological rejection is alleviated because the patient’s own genetic material is used. If a cell line were created with cells from another individual, the patient’s body would be more likely to recognise the foreign proteins and then wage an attack on the transplanted cells. The ultimate consequence would be a rejected stem cell transplant. This is one of the major challenges of organ transplants, alongside the fact that there is a huge shortage of available organs for those who require the procedure. This means that therapeutic cloning has the potential to dramatically reduce the wait times for organ transplants as well as the immunological concerns associated with organ transplant therapy.
Therapeutic cloning is also important to enhancing our understanding of stem cells and how they and other cells develop. This understanding can hopefully lead to new treatments or cures for some of the common diseases affecting people today. In addition, the procedure would allow for scientists to create stem cell therapies that are patient specific and perfectly matched for the patient’s medical condition.
One problem with therapeutic cloning is that many attempts are often required to create a viable egg. The stability of the egg with the infused somatic nucleus is poor and it can require hundreds of attempts before success is attained.
Therapeutic cloning does result in the destruction of an embryo after stem cells are extracted and this destruction has stirred controversy over the morality of the procedure. Some argue that the pros outweigh the cons with regards to treating disease whilst others have likened the destruction to an abortion. Still others state that this doesn’t change the fact the embryo could potentially be a human being and so destruction of the embryo is no different than destruction of a human life.
Because reproductive cloning does utilise SCNT as the primary step, there is also still fear that given our knowledge base to perform reproductive cloning, a scientist may attempt to move beyond therapeutic cloning to creation of a human being.
To this date, no human being has been successfully cloned but the possibility of this occurring is a frightening one not only for the general public and policy makers, but also for most of the ethical scientific field. The majority of scientists are adamantly opposed to reproductive cloning and instead, support therapeutic cloning for treating disease. With policies and careful monitoring in place to ensure that therapeutic cloning is used responsibly, we can all benefit from the potential of this procedure to eventually treat, or perhaps one day cure, many diseases.
The bishops of the United States will meet in San Antonio next month and there is a new agenda item for them: Deal with the fallout from the controversy surrounding Notre Dame’s bestowal of an honorary degree upon the President.
At the center of that debate has been a document the bishops issued in 2004 entitled “Catholics in Political Life.” As the title indicates, it was unclear to many of us, including Notre Dame’s President, Father John Jenkins, C.S.C., why a document so entitled would even apply to President Obama who is not a Catholic at all. And the text was issued by a committee set up to focus on (and the text only refers to) “Catholic politicians.” Bishop John D’Arcy replied that if there was any question, Father Jenkins should have asked him. To clarify for everyone, however, the bishops need to decide if the document and the strictures it contemplates are meant to apply to everyone or just to Catholics.
Most opponents of Notre Dame’s decision to honor the President focused on one part of the text: “The Catholic community and Catholic institutions should not honor those who act in defiance of our fundamental moral principles.” Now, it is a fair question whether Barack Obama, in promising policies that seek to reduce the abortion rate, is acting in defiance of anyone’s fundamental moral principles. (The abortion reduction language he used throughout the campaign and again at Notre Dame certainly annoys and angers some pro-choice activists.) There was a time when Catholics could be skeptical of the claim by some that they were “pro-choice but not pro-abortion” but Obama seems to making that a distinction with a difference.
It is also the case that virtually every American politician acts in defiance of some fundamental principle of the Catholic Church. Former Vice-President Dick Cheney is justifying the use of torture (and his arguments are echoed on EWTN) by invoking the age old maxim that the ends justify the means, but that is a utilitarian principle not a Catholic one. Nor is the recourse to the category of intrinsic evil much help here. Lots of things are intrinsically evil including birth control and as I have pointed out before there is not a mayor nor a governor who does not sign a budget that funds some form of birth control policy.
Commentators have tended to ignore the second sentence in the document’s bullet point on the conferral of honors: “They should not be given awards, honors or platforms which would suggest support for their actions.” Now, I thought Father Jenkins made it very clear, both in his initial announcement in March and at the commencement ceremony on Sunday, that Notre Dame was not honoring the President because of his positions on abortion and embryonic stem cell research but for his other notable accomplishments. The bishops may want to strike this sentence and say – do not honor these guys period. But, any fair-minded person would be wrong to fault Father Jenkins for violating this document when you read it in its entirety.
So, the bishops have their work cut out for themselves at San Antonio. I suspect that at the end of the day, the authority of the local bishop in such matters will, and should, be highlighted. As Archbishop Donald Wuerl of Washington, one of the most thoughtful and theologically sophisticated bishops in the country, wrote in his weekly column last week discussing this very document, “While everyone may not agree with how an individual bishop applies this principle for institutions within his own diocese, it, nonetheless, is the bishop’s call.” That may not make everyone happy – indeed, it won’t make everyone happy. But, the central role of the bishop as teacher within his diocese is more important than any political point. Yes, some bishops may turn their universities into intellectual ghettoes, allowed to invite no one with a differing or provocative position to campus. Others will follow James Joyce’s view: “Here comes everybody!” But, as Wuerl said, at the end of the day, in a hierarchical church, it’s the bishop’s call.
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