Thesis: Ethical Debates Surrounding Stem Cell Research

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[. . .] What follows is a brief description of the primary types of human stem cells that have captured the interest of scientists, clinicians, ethicists, policymakers, and religious organizations.

Fetal stem cells. The most controversial stem cells are those derived from human embryos, but in contrast to adult stem cells, these are truly pluripotent and therefore have captured the attention of biologists and medical scientists interested in understanding human development and how these cells could be used to treat and possibly cure disease (Blow, 2008). ES cells have been derived from discarded embryos generated during in vitro fertilization (IVF) treatments (National Institutes of Health, 2002). Typically, multiple oocytes are fertilized during IVF procedures and only a select few are transferred to the womb. The remaining fertilized embryos have been discarded in the past, but a few scientists have requested and been given permission by parents to harvest the cells from the inner cell mass (Shand, Berg, Bogue, Committee for Pediatric Research, & Committee on Bioethics, 2012). The cells derived from the inner cell mass of fertilized blastocysts are theoretically totipotent, which implies that this technology could be used to clone human beings. Accordingly, many ethicists, policymakers, and religious organizations view this technology as morally objectionable. In addition to having the potential to differentiate into any number of cellular phenotypes, human ES cells can continue to divide in vitro for much longer than adult stem cells harvested from other tissues.

Umbilical cord blood. Human umbilical cord blood has been banked in multiple locations for over a decade and has been the source of hematopoietic stem cells for children requiring bone marrow transplants (National Institutes of Health, 2002). In some cases the cord blood has come from the same children needing treatment, so there is little chance that the transplant will be rejected. More recent research has revealed that umbilical cord blood contains cells that can be reverted in vitro to resemble the pluripotency commonly associated with ES cells, thereby increasing the potential uses of this source of stem cells (Salk Institute, 2009). Stem cells isolated from cord blood are also immunologically immature, which makes host rejection less likely even when there is a mismatch between the donor and recipient.

Placenta-derived stem cells. The placenta is typically discarded during delivery of the newborn, but recently it has been recognized to be a rich source of multipotent stem cells (Caruso, Evangelista, & Parolini, 2012). In comparison to umbilical cord blood, however, cells isolated from the placenta tend to be more differentiated and less like ES cells in phenotype. The restriction in potency has not discouraged researchers from investigating and testing the efficacy of placental-derived stem cells in regenerative medicine and the results have been encouraging. Distinct locations within the placenta seem to be enriched in cells with stem cell-like properties and can give rise to multiple phenotypes for a given lineage, such as skin and muscle.

Adult stem cells. Researchers over the past two decades have come to realize that adult tissues contain a small number of stem cells (Shand et al., 2012). These stem cells can be found in the bone marrow, skin, heart, connective tissue, and brain and have been successfully isolated for research and clinical purposes. In fact, the use of bone marrow transplants to reconstitute the hematopoietic cell types in pediatric leukemia patients is considered best practice for this patient population. The use of stem cells from other tissues has mainly focused on tissue regeneration, since these cells tend to be more differentiated and therefore more restricted (multipotent) in what cellular phenotypes they can give rise to. In addition, it has been difficult to expand these types of cells to numbers sufficient for multiple uses or clinical applications; however, the risk of tumor formation after transplantation is very low.

Induced pluripotent stem cells (iPSCs). As mentioned in the introduction, somatic cells from adults have been successfully reverted to a less differentiated phenotype (Easley et al., 2014). Although the term 'iPSCs' suggests these cells are pluripotent, researchers have so far been unable to revert adult somatic cells to a true pluripotent state. Some researchers would argue, however, that reversion to a pluripotent state may not be desirable since a more differentiated state tends to be more stable and less likely to contribute to tumor formation. This is one of the primary concerns of generating pluripotent stem cells from adult somatic cells, in addition to concerns about accumulated genetic mutations and other abnormalities. By comparison, stem cells derived from fertilized embryos or umbilical cord blood would be genetically more intact and free of other abnormalities. Researchers are making progress in this area and the first clinical trial was begun last year in Japan for the treatment of macular degeneration (NIH, 2012).

Harvesting Stem Cells

The harvesting of human ES cells from fertilized embryos typically involves the destruction of the blastocysts and the isolation of the cells that make up the inner cell mass (Shand et al., 2012). Although there have been laboratory attempts to isolate one or two cells from an intact embryo, thereby sparing the embryo from destructions, researchers have not determined whether this technique reduces the viability of the embryo. One of the main reasons for developing a harvesting technique that spares the embryo is to avoid the ethical dilemma of destroying a potential human life.

Since umbilical cord blood has historically been considered a waste product in Western societies the ethical concerns surrounding the harvesting of ES cells from fertilized human embryos are avoided. For this reason, considerable effort is being invested in improving the harvesting techniques for stem cells from cord blood (Danby & Rocha, 2014). The main limitations of its use for clinical applications are the small number of stem cells that can be recovered from a single donation. During delivery the cord is clamped and the blood removed using a syringe containing heparin (Demerdash et al., 2013). For bone marrow transplantation the nucleated cells are recovered using centrifugation and injected into the femur of patients who have undergone chemotherapy or radiation treatment (Danby & Rocha, 2014). Since the number of hematopoietic stem cells is so small, this technique is limited to children or small adults, although double cord blood transplants have been used successfully. For research purposes, nucleated cells isolated from cord blood by centrifugation can be cultured for 10 days and the stem cells will form colonies of adherent cells (Demerdash et al., 2013). These can then be recovered, expanded, and then differentiated into a defined phenotype before clinical application.

While the isolation of stem cells from umbilical cord blood may seem technically challenging, the isolation of adult stem cells from tissues is much more difficult and painful for the donor (De Sa Silva et al., 2012). Bone marrow donations are obtained by boring a hole into the center of a large bone and withdrawing the marrow. The bone marrow is not only a source of hematopoietic stem cells, but also mesenchymal stem cells that can give rise to a number of cellular phenotypes, including bone, connective tissue, muscle, adipose tissue, and stroma (Murphy & Atala, 2013).

By comparison, the harvesting of somatic cells for generating hiPSCs can be relatively simple and pain-free (Verma & Verma, 2011). Among the first cell types harvested were skin fibroblasts, which can be isolated from a skin biopsy and expanded ex-vivo. Pluripotency is then induced using a cocktail of transcription factors, which some researchers have reported as ridiculously easy and reproducible.

Stem Cells in Medicine

Currently, the use of ES and hiPSCs for tissue regeneration is limited to laboratory research because these cells tend to produce teratomas and other tumors when transplanted into a host (Verma & Verma, 2011). Should this hurdle be overcome, then the applications are theoretically limitless, from the repair of damaged or diseased tissue, including brain and heart tissue, to growing a new organ in a culture dish in preparation for transplantation. The main advantage that hiPSCs have when compared to ES cells is that they could be harvested from and used to treat the same patient. This would eliminate or reduce the need for immunosuppressive drugs to prevent host rejection of the transplanted tissue.

Currently, all stem cell clinical applications are based on the use of adult stem cells. The tissue sources of stem cells in common use are bone marrow, cord blood, and peripheral blood (O'Meara et al., 2014). Each source has its own unique advantages and disadvantages. UCB, for example, contains only a small number of hematopoietic stem cells, which restricts its use to reconstituting the hematopoietic system in children and small adults (Danby & Rocha, 2014). The primary limitation of adult stem cells, including umbilical cord blood, is therefore the ability to transfer a large number of cells into the patient. Researchers are working on this problem and at least one study reported expanding a mesenchymal stem cell population derived from cord blood sufficiently to meet most clinical applications (Luo et al., 2010). The mesenchymal stem cells could be used for… [END OF PREVIEW]

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Ethical Debates Surrounding Stem Cell Research.  (2014, March 15).  Retrieved May 25, 2019, from https://www.essaytown.com/subjects/paper/ethical-debates-surrounding-stem-cell/5970689

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"Ethical Debates Surrounding Stem Cell Research."  Essaytown.com.  March 15, 2014.  Accessed May 25, 2019.
https://www.essaytown.com/subjects/paper/ethical-debates-surrounding-stem-cell/5970689.