Insulin-producing cells derived from stem cells: A potential treatment for diabetes
Insulin was discovered over 75 years ago, however the complications of diabetes still produce devastating results (Bonner-Weir et al., 2006). Such complications are retinopathy, nephropathy and neuropathy which link between high blood glucose levels are now established beyond doubt (Bonner-Weir et al., 2006). Thus, β-cell replacement therapy in the form of transplantation would be a great path to prevent the complications. “Β-cell is defined as a cell with the phenotype of a mature insulin-producing cell found in pancreatic islets”(Bonner-Weir et al., 2006, p.411). Nevertheless, the supply of insulin-producing cells is insufficient thus limits the extension
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Wang et al. (2012) stated that, one of the abundant source of adult stem cells is bone marrow. According to Weir et al. (2006), there is high possibility in circulating bone marrow cells could serve as precursors for a wide variety of cells scattered throughout the body. Cells other than true hematopoietic stem cells derived from bone marrow can serve as circulating stem or precursor cells. It has recently been shown that impressive repopulation of destroyed liver tissue can be generated from bone marrow cells. In addition, rather than a precursor, bone marrow cells could contribute to new β–cell formation as a facilitator Bonner-Weir et al., 2006, p.411). Moreover, current study suggests that bone marrow contains pluripotent cells that are capable of being reprogrammed in order to differentiate into insulin-producing cells (Wang et al., 2012).
Next, liver also works as a source of insulin-producing cells. Liver cells not only secreted insulin in a regulated manner but also reversed diabetes when transplanted into immunodifficient diabetic mice (Bonner-Weir et al., 2006, p.416). Pandey (2010) stated that, the liver appear to arise from the same cell population located within the embryonic endoderm during embryogenesis. Assumption has been done where the epithelial cell populations within the liver might share common stem cell populations (Pandey, 2010). Thus, another source for β-cells would be liver stem cells. “Upon transplantation into diabetic mice, these
The first type of stem cell, an embryonic stem cell, is known for being able to continuously multiply, as well as for being pluripotent. They can be “derived in vitro from the blastocyst of an embryo usually left over from in vitro fertilization” (Forraz & McGuckin, 2011, p.61). Unlike other types of stem cells, embryonic stem cells have yet to be used in any kind of clinical treatment of patients. The high risks of “immune rejection” or “teratoma formation” are serious obstacles (Harris, 2009, p.182). The second type of stem cell, adult stem cells, is primarily considered to be multipotent and may be found in “specific adult human tissues” such as the skin or bone marrow, just to name a few. Over the last twenty years, the amount of scientific research and trials using adult stem cells has grown significantly, despite their lower potency than embryonic stem cells (Forraz & McGuckin, 2011, p.61). Lastly, cord blood stem cells, are technically considered to be a special type of adult stem cell, but their youthful properties give them “greater restorative and regenerative potential.” Directly following the birth of a child, these stem cells can be collected from the blood in the umbilical cord (Steenblock & Payne, 2006, p.9). Embryonic, adult, and cord blood stem cells
First of all an understanding of what a stem cell is, where it comes from, and the significance of it's medical potential is essential. Stem cells are the "master cells" that form the human body or whatever other animal it is from. Stem cells can be extracted from adult tissues, bone marrow, umbilical cord blood ( ), and embryos in the blastocyst stage. Although scientists have found ways to manipulate the stem cells from adult sources into other types of cells, they claim that they are less capable of deriving the desired tissue and are not "biologically equivalent" ( ) to stem cells extracted from embryos.
The process when stem cells give rise to blood cells, or any other specialized cells, is called differentiation (“Stem Cell Basics”). Stem Cells’ ability of differentiation can be targeted and directed to generate tissue and therefore to cure degenerative diseases (Panno 24-28). However, such medical promise faces the doubts and gives rise to disputes. In fact, federal funds for stem cell research were banned under President Bush’s administration, but the ban was then lifted by President Obama’s administration (Obama). Despite the different arguments, more medical trials should be conducted with embryonic stem cells in order to determine whether the medical promise is applicable or far-fetched.
Initially the results of islet cell transplantation were dismal but after the induction of glucocorticoid free immunosuppressive therapy and the use of adequate number of islet cells from multiple donors, showed a significant improvement in β – cell function with insulin independence 9. However, islet cell transplantation has its own limitations viz-insufficient supply, technically demanding and use of life -long immunosuppressive therapy in the recipients and progressive insulin dependence. These shortcomings can be overcome by the use of stem cells, which is an inexhaustible source of β –cells.
“Through the isolation and manipulation of cells, scientists are finding ways to identify young, regenerating ones that can be used to replace damaged of dead cells in diseased organs. This therapy is similar to the process of organ transplant, only the treatment consists of the transplantation of cells rather than organs. The cells that have shown by far the most promise of supplying diseased organs with healthy cells are called stem cells.” (Chapter Preface)
The controversy of stem cell therapy is mainly dependent on whether its advantages outweigh the disadvantages, its plasticity and degree of differentiation, availability are also of great deal to carrying out stem cell transplantation (Habib and Gordon, 2006).One of the advantages of adult stem cells is that they can be found in a number of tissues and organs in the body, and can be acquired using a variety of techniques depending of which type of stem cells are needed to be collected (Habib and Gordon, 2006). Their high differentiation potential to regenerate the tissue or organ that they will reside in and cure is beyond the required threshold for the success of the procedure. For bone marrow stem cell transplantation, the long-term experience of performing the procedure and the familiarity
(Hermanns-Le, Scheen, & Pierard, 2014, p. 200) As our cells fail to respond to insulin, the beta cells of the pancreas produce more insulin and trigger the liver to produce more glucose to restore glycemic control. This compensational mechanism will eventually be unable to keep up with the body’s demands leading to elevated glucose levels in circulation. Eventually, the high demand of pancreatic beta cells to produce insulin will not be able to keep up and insulin production will become insufficient, lessening the uptake of glucose. This now opens the path to Type II Diabetes Mellitus. (Thoenes, 2012, p. 621)
Both type 1 and 2 diabetics result from a complete or partial loss of beta cell number and function. Currently they are working on regenerating human beta cells. They are also in trail with the creation of an artificial pancreas. This is to replace the damaged pancreas so that the new pancreas can provide insulin to the
Diabetes is one the most critical medical issues of our time. According to the Center of Disease Control and Prevention nearly 26 million Americans (approximately 8% of all Americans) have diabetes and an estimated of 79 million adults are pre-diabetes. Approximately $200 billion per year is lost due to diabetes because of medical treatments and lost wages. Insulin resistance and the dysfunction of beta cells are the two pathogenic hallmarks of the development and progression of T2DM. Studies have shown that pancreatic beta cell functional mass is affected in T2DM (1, 2). Secretion of insulin stimulated by glucose is lower in human islets of Langerhans isolated from patients with T2DM than from normal individuals (1, 3). Knowledge of the molecular mechanism underlying defects in beta cell function found in humans and animal models of T2DM is incomplete. Without a more complete understanding of the mechanisms that regulate beta cell insulin secretion we will be unable to develop new approaches to prevent and treat diabetes.
Several people in the United States suffer from diabetes. Some of the worst cases can cause kidney failure and even death. Type 1 diabetes is an autoimmune metabolic condition which kills off all the pancreatic beta cells that produce the insulin needed for glucose regulation in the body. (2) Finding a cure for type 1 diabetes would be one of the most successful thing we can do. By testing a human insulin producing cell, we can see if injecting a type 1 diabetic with the insulin producing cell that would then help generate their own insulin producing cells.
Without beta cells obviously the body cannot produce insulin in response to high blood glucose, causing type 1 diabetics to have abnormally high blood sugar
We've known for some time that bone-marrow stem cells can make more blood, but now we know that these adult stem cells can also make bone, muscle, cartilage, heart tissue, liver, and even brain. Interestingly enough, we now know that our brain contains stem cells which can be stimulated to make more neurons, or to take up different job descriptions as muscle or blood. Bone marrow and cord blood are already successfully being used clinically, while clinical use of embryonic stem cells is years away. Current clinical applications of adult stem cells include treatments for cancer, arthritis, lupus, and making new corneas, to name a few.
As the pancreas releases increased amounts of insulin, due to the high sugar blood levels which is one of the major changes in the body. The pancreatic beta cells hyperplasia and hypertrophy, however as it progress the process reverses and cells being to hypotrophy and undergo hypoplasia, and the pancreas decreases in size significantly (Yagihashi).
In the control group, the β-cells were pale stained and located centrally surrounded by the α-cells. The Islets were fairly numerous surrounded by the sero-acinar cells which were well stained and comprised of the exocrine component of pancreas. In the diabetic group, there were necrotic and atrophic features in most β-cells of Islets of Langerhans and vacuoles were present. There was a marked reduction in the number of islets. Following treatment with 400 mg/kg of fenugreek + 250 mg/kg of metformin, there was a marked increase in the number of functioning β-cells with restoration of normal volume density nearly similar to that of the control group.
Stem cells offer much hope for medical advancement because of their ability to grow into almost any kind of cell. Stem cells are crucial to develop organisms. They are non-specialized cells which have the remarkable potential to develop into many different cell types in the body during early life and growth. Because stem cell are a non-specialized cell can develop into any cell it wants within the organism it inhabits without limit to replenish other cells as long as the person or animal is still alive. Which mean under experimental condition, they can be induced to become tissue or organ- specific cell with special function? In some organs such as the gut and the bone marrow, stem cell regularly divide to repair and replace worn out or damaged tissues.