Today’s New Reason To Believe

Breakthrough May Revolutionize Stem Cell Research

Originally posted on July 19th, 2007

I have always wanted to have my cake and eat it too, but alas, that have-it-all scenario is not possible. Or is it? Breakthroughs by scientists from Kyoto University in Japan and MIT and Harvard University in the US now make it possible to generate embryonic-like stem cells (ELSCs) without destroying human embryos. These research teams produced ELSCs from mice adult skin cells. Neither eggs nor embryos were necessary.

The biomedical community hopes that embryonic stem cell research (ESCR) will lead to techniques that can generate replacement tissues from embryonic stem cells (ESCs). They claim that implanting replacement tissue derived from ESCs into damaged and diseased organs provides the means to treat and possibly cure many horrendous diseases and debilitating injuries. Unfortunately, in order to harvest stem cells from human embryos, the embryo must be destroyed.

In addition to ethical concerns, use of ESCs is riddled with several serious technical problems. Perhaps the largest hurdle facing this biotechnology is rejection due to genetic mismatch between the ESCs and the patient. This problem is identical to rejection that can occur after organ transplant procedures. If the donor and recipient are not compatible, the recipient’s body rejects the organ. It’s almost certain that the recipient’s body will treat genetically incompatible ESCs as foreign material and reject the cells before they can deliver any promised benefit.

Both research teams were able to transform skin cells called fibroblasts into ELSCs by transferring four genes into these easily isolated cells using a retrovirus as a carrier. The ELSCs can develop into all the different cell types in the human body, just like ESCs. ELSCs don’t raise any ethical concerns, however, since they derive from adult cells, not embryos. Biomedical applications of ELSCs won’t be frustrated by rejection because the fibroblasts used to produce them can be taken from the patient.

At this point, it is not clear if human fibroblasts can be coaxed to form ELSCs. Safety concerns are also a factor. Researchers are troubled by the use of a retrovirus to introduce genes into the fibroblast. They are also cautious because one of the transforming genes is involved in tumor formation. Still, the initial results are exciting and future work should address these potential pitfalls.

The discovery of methods to generate ELSCs from adult fibroblasts augments exciting advances already taking place with adult stem cells. These cells can be readily isolated from adult tissues like scalp, dental pulp, bone marrow, the olfactory bulb, the umbilical cord, and the placenta. No embryos are destroyed and no human life is lost in the process of isolating adult stem cells.

Numerous new discoveries indicate that several types of adult stem cells behave like embryonic stem cells. Under laboratory conditions these adult stem cells can be coaxed to develop into a wide range of cell types that are suitable for use in tissue replacement therapies. An increasing number of biomedical researchers are focusing their efforts on adult stem cells. The number of papers published in scientific journals on adult stem cells and their potential as therapeutic agents is growing week by week. Use of adult stem cells in tissue replacement therapies has an added advantage. Adult stem cells do not suffer from the problems associated with use of embryonic stem cells, like rejection and tumor formation.

As biomedical applications for adult stem cells (and hopefully ELSCs) matriculate to clinical applications, treatments for diseases and injuries that cause dreadful human suffering will be available without requiring the destruction of human embryos. That prospect leaves a good taste in my mouth.

Now if only someone could come up with cake that can be eaten without causing weight gain…

For more information on stem cell research see “A collection of interview questions posed to, and answered by, Dr. Fazale “Fuz” Rana.â€?

Breakthrough May Revolutionize Stem Cell Research

I have always wanted to have my cake and eat it too, but alas, that have-it-all scenario is not possible. Or is it? Breakthroughs by scientists from Kyoto University in Japan and MIT and Harvard University in the US now make it possible to generate embryonic-like stem cells (ELSCs) without destroying human embryos. These research teams produced ELSCs from mice adult skin cells. Neither eggs nor embryos were necessary.

The biomedical community hopes that embryonic stem cell research (ESCR) will lead to techniques that can generate replacement tissues from embryonic stem cells (ESCs). They claim that implanting replacement tissue derived from ESCs into damaged and diseased organs provides the means to treat and possibly cure many horrendous diseases and debilitating injuries. Unfortunately, in order to harvest stem cells from human embryos, the embryo must be destroyed.

In addition to ethical concerns, use of ESCs is riddled with several serious technical problems. Perhaps the largest hurdle facing this biotechnology is rejection due to genetic mismatch between the ESCs and the patient. This problem is identical to rejection that can occur after organ transplant procedures. If the donor and recipient are not compatible, the recipient’s body rejects the organ. It’s almost certain that the recipient’s body will treat genetically incompatible ESCs as foreign material and reject the cells before they can deliver any promised benefit.

Both research teams were able to transform skin cells called fibroblasts into ELSCs by transferring four genes into these easily isolated cells using a retrovirus as a carrier. The ELSCs can develop into all the different cell types in the human body, just like ESCs. ELSCs don’t raise any ethical concerns, however, since they derive from adult cells, not embryos. Biomedical applications of ELSCs won’t be frustrated by rejection because the fibroblasts used to produce them can be taken from the patient.

At this point, it is not clear if human fibroblasts can be coaxed to form ELSCs. Safety concerns are also a factor. Researchers are troubled by the use of a retrovirus to introduce genes into the fibroblast. They are also cautious because one of the transforming genes is involved in tumor formation. Still, the initial results are exciting and future work should address these potential pitfalls.

The discovery of methods to generate ELSCs from adult fibroblasts augments exciting advances already taking place with adult stem cells. These cells can be readily isolated from adult tissues like scalp, dental pulp, bone marrow, the olfactory bulb, the umbilical cord, and the placenta. No embryos are destroyed and no human life is lost in the process of isolating adult stem cells.

Numerous new discoveries indicate that several types of adult stem cells behave like embryonic stem cells. Under laboratory conditions these adult stem cells can be coaxed to develop into a wide range of cell types that are suitable for use in tissue replacement therapies. An increasing number of biomedical researchers are focusing their efforts on adult stem cells. The number of papers published in scientific journals on adult stem cells and their potential as therapeutic agents is growing week by week. Use of adult stem cells in tissue replacement therapies has an added advantage. Adult stem cells do not suffer from the problems associated with use of embryonic stem cells, like rejection and tumor formation.

As biomedical applications for adult stem cells (and hopefully ELSCs) matriculate to clinical applications, treatments for diseases and injuries that cause dreadful human suffering will be available without requiring the destruction of human embryos. That prospect leaves a good taste in my mouth.

Now if only someone could come up with cake that can be eaten without causing weight gain…

For more information on stem cell research see A collection of interview questions posed to, and answered by, Dr. Fazale “Fuz” Rana.

Xenotransplantation: Another Alternative to Embryonic Stem Cell Research

More than one woman has exclaimed, “Men are pigs!” Ongoing biomedical advances may well make this sentiment much more than a metaphorical insult as researchers explore the possibility of using pigs as a source of organs for transplant procedures.

The idea of transplanting organs from animals into humans (xenotransplantation) is not new. But the genuine hope of making this practice a viable medical procedure is. The prospect of xenotransplantation promises to save human lives—not just by providing desperately needed organs for transplant procedures, but by obviating the need for tissue-replacement procedures based on embryonic stem cells.

A perspectives article published in PLoS Medicine summarizes some of the recent scientific breakthroughs. These discoveries have prompted scientists to seriously consider xenotransplantation as a possible means to close the widening gap between the organs required and the organs available for transplant.¹

One of the chief hurdles for xenotransplantation from pigs to humans is hyperacute rejection(HAR). When pig organs are transplanted into primates, rejection occurs within minutes due to the presence of a cell surface sugar (α 1,3-galactose). This sugar is present in most mammals, but absent in primates (which includes humans). This cell surface sugar elicits a vigorous immune response by the primate organ recipient.

There are good prospects for overcoming this problem. Researchers have genetically engineered and cloned pigs that lack a functional gene for 1,3-galactosyltransferase, the enzyme that adds α 1,3-galactose to the cell surface. Organs from these genetically engineered pigs are not immediately subjected to HAR when implanted into baboons (a laboratory stand-in for humans), but the organs are eventually rejected. This rejection is caused by antigens that have no relation to α 1,3-galactose.

Still, biomedical researchers have been able to achieve organ survival up to 6 months in baboons when immune suppressants are administered. Unfortunately, the levels of immune suppressants that are required leave the organ recipient unusually susceptible to infection.

The good news is that these and other studies have led to improved understanding of the immune mechanisms responsible for organ rejection. And the new insights suggest ways to disrupt these immune pathways. Exploratory work toward this end is already underway.

Another problem facing xenotransplantation involves increased susceptibility to infection by pathogens that are not normally associated with human diseases. This vulnerability stems from both the compromised state of the immune system (due to the necessary administration of immune suppressants) and the exposure to pig-specific pathogens. Porcine endogenous retroviruses (PERVs) are of particular concern. PERVs are viruses that have been incorporated into pig genetic material. Researchers have shown that in a laboratory setting, PERVs can infect human cells. This raises concerns that PERVs could infect human cells after an organ transplant, unleashing novel diseases among humans. While this concern can’t be minimized, it’s noteworthy that people have been treated with pig tissues for years with no evidence of PERV infections. Also, selective breeding practices could dramatically reduce the number of pathogens associated with the pig organ donors. For example, swine breeds that don’t express human-infectious PERVs have been identified.

All-in-all, excellent progress has been made in pig-to-human xenotransplantation. Clearly, difficulties abound, but the future prospects for xenotransplantation look good. As Muhammad M. Mohiuddin, the author of the PLoS Medicine article notes: “research in this field is progressing in the right direction.”²

The greatest hindrance to xenotransplantation, however, is not scientific, it’s monetary. Currently, limited funding is available to support research efforts in xenotransplantation.

The lack of funding for xenotransplantation is tragic. Pro-life advocates need to speak out in support of xenotransplantation and campaign for increases in federal and state funding for this research program. This procedure serves as another important alternative to embryonic stem cell research (ESCR).

The biomedical community hopes that ESCR will lead to techniques that can generate replacement tissues from embryonic stem cells(ESCs). The claim is that implanting replacement tissue derived from ESCs into damaged and diseased organs provides the means to treat and possibly cure many horrendous diseases and debilitating injuries. Unfortunately, in order to harvest stem cells from human embryos, the embryo must be destroyed.

Use of pig organs for transplant procedures could be used in place of tissue replacement procedures in some instances, particularly in cases of severe organ damage.

One day men (or least parts of them) really may be pigs. And they may be alive, enjoying an improved quality of life because of it—without having to destroy human embryos for their stem cells.

For more information on ESCR and ethically acceptable alternatives see Embryonic Stem Cell Research: A collection of interview questions posed to, and answered by, Dr. Fazale “Fuz” Rana. ¹ Muhammad M. Mohiuddin, “Clinical Transplantation of Organs: Why Aren’t We There Yet?” PLoS Medicine 4 no. 3 (2007): e75. ² Muhammad M. Mohiuddin, e75.