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1. What is the difference between embryonic stem cells and adult stem cells?

Embryonic stem cells are derived from the inner cell mass of the embryos. They are derived from eggs fertilized in vitro using in vitro fertilization. Embryonic stem cells are not derived from eggs fertilized naturally in a woman’s body. When embryonic stem cell line hae proliferated in cell culture for a long time without differentiating, they are pluripotent, and have not developed genetic abnormalities. Embryonic stem cells can be identified by testing if the cell remain undifferentiated. The presence of transcription factors called Nanog and Oct4 are associated with stem cells maintaining an undifferentiated state capable of self-renewal.

Adult stem cells are undifferentiated cell that are found among tissue or organ. Adult stem cell can renew itself and can differentiate to yield some major specialized cell types of the tissue or organ. The function of adult stem cell is to maintain and repair the tissue in which they are found.

The major difference between embryonic stem cells and adult stem cells is that they have different abilities in the number and type of differentiated cell types they can become. For example, embryonic stem cells are pluripotent and can become all cell types of the body. Adult stem cells are limited to differentiating into different cell types of their tissue of origin. Adult stem cells are challenging to grow in culture, but embryonic stem cells are easy to culture. Adult stem cells are less likely to initiate rejection after transplantation compared to embryonic stem cells because adult stem cells are derived from the patient’s own adult stem cells and would be less likely to be rejected.

2. What are the limitations of embryonic stem cells?

Embryonic stem cells has many disadvantages. First, one disadvantage of using embryonic stem cells in transplantation is that they require lifelong use of immunosuppressive drugs to prevent rejection of the embryonic stem cells. Secondly, another disadvantage is that embryonic stem cells can induce more tumors when injected into the adult patients. The third disadvantage is that it can produce dramatic side effects when injected into other tissues such as the brains as was reported by the New England Journal of Medicine. The fourth disadvantage of using embryonic stem cell is that they are genetically unstable when introduce into other cells as evidence from genetically defective mice cloned from embryonic stem cells.

3. What therapies are adult stem cells currently used in?

Human mesenchymal stem cells are currently used in therapies to protect pancreatic beta isledt cells in adults and children with newly diagnosed type 1 diabetes. It is also use for the repair of heart tissue following a heart attack.

They are also use for the repair of lung tissue in patients with chronic obstructive pulmonary disease.

Adult Eye stem cells for eye disease or damage is another therapy. For example, scientist are testing whether the limbal stem cells can help repair damage to the cornea of the eye. They are testing whether they can replace cells that are lacking due to the limbal stem cell deficiency.

4. Why ( from a regenerative medicine perspective) are we interested in stem cells and paracrine signaling?

The potential for stem cells to replace defective tissues is promising. Today, there are fewer donated organs and tissues available in the pool for the vast number of people who need them for transplantation. The pluropotent stem cells offer the possibility to renew a defective tissues or cells. Pluropotent stem cells can replace old cells and can regenerate new tissues to treat Parkinson’s disease, spinal cord injury, diabetes, and arthritis.

There is a growing hypothesis that paracrine signaling can help the regeneration process of stem cells. Paracrine mechanisms are mediated by factors released by adult stem cells, which can play essential role in the regeneration of tissues. Adult stem cells (ASCs) produce and secrete many paracrine signals, including cytokines, chemokines, and growth factors. These paracrine signals may play a role in cardiac repair. For example, paracrine factors like vasculuar endothelial growth factor (VEGF), basic fibroblast growth factor, hepatocyte growth factor (HGF), insulin like growth factor (IGF)-I, and adrenomedullin are all significant in increasing the injured hearts. The paracrine signals can influence other cells adjacent to each others through several mechanisms. Some of the stem cells that the paracrine signals can influence are cardiomyocytes, endothelial cells, smooth muscle cells, fibroblasts, and cardiac stem cells. Once these stem cells are activated by the paracrine signals, they can exert mycocardial protection, cardiac metabolism, contractility, cardiac regeneration, neovascularization, and cardiac remodeling. These released factors may have autocrine actions on the stem cells themselves. (2)

5. How might stem cells and gene therapy converge to enable tissue regeneration?

Stem cells and gene therapy may converge to enable tissue regeneration by using gene therapy to introduce the stem cells into the defective tissues. This is being tested for the hyaline articular cartilage. The function of cartilage is to protect bones of the joints from frictions and forces associated with load bearing and impact. Once the articular cartilage is injured, it is very hard for self-repair and regeneration. In focal cartilage defects, the surgeons try to promote the natural fibrocartilaginous response by using marrow stimulating techniques such as microfracture, abrasion arthroplasty , and pride drilling. However, fibrocartilage presents inferior mechanical and biochemical properties compared to normal hyaline articular cartilage, characterized by poor organization, significant amounts of collagen type I, and increased injury.

Therefore, the implementation of gene transfer techniques may allow to overcome the limitations of the current treatments for articular cartilage lesions. In gene therapy. The gene delivery system for cartilage repair and restoration include a gene delivery system for a particular tissue. In gene therapy, the complementary DNA (cDNAs) are transfer into the defective tissues. The cDNAs include members of the transforming growth factors (TGF-B), morphogenetic proteins (BMPs), insulin-like growth factor( IGF)-1, fibroblast growth factors (FGFs), and epidermal growth factor ( EGF). The delivery of cDNA encoding extracellular matrix (ECM) components such as collagen type II or other tissues may also be used.

Gene delivery system can also transfer cDNA encoding specific stem cells into the site of injuries. However, the application of this technology is strongly dependent on the use of safe and efficient delivery systems vectors and transgenes. (3)

References

1. http://www.icr.org/article/ten-problems-with-embryonic-stem-cell-research/

2. Gnecchi et al. Paracrine Mechanisms in Adult stem cells signaling and therapy. Circulation Research. 2008.

3. Longo et al. 2012. Stem cells and Gene Therapy for Cartilage Repair. Stem cells International.