Advances in biotechnology have opened up newer areas of cell based therapies to treat diabetes like:
1. Use of adult stem cells as possible precursors to islet cells
2. Use of embryonic stem cells
The development of stem cell based therapies to treat diabetes depends on certain criteria:
• The stem cells should be capable of self-renewing. In other words they should be able to multiply in culture and replicate
• They should be able to make the desired kind of cells in vivo.
Should stem cells be coaxed to produce only beta cells or other types of cells too?
The question whether stem cells should be induced to produce only beta cells or beta cells plus other types of pancreatic islet cells remains vexed.
However researchers Bernat Soria and others have shown that intact islet clusters with all types of islet cells are more responsive to blood sugar changes than isolated beta cells. This is because they release insulin in two stages encompassing a quick release mechanism that releases high concentrations of insulin and a slower release mechanism that involves low concentrations of insulin. This way the beta cells can adjust their response to changing blood sugar levels.
What this research has shown is that isolated beta cells don't work the same way as clusters of islet cells which includes non-beta cells as well. The former cannot handle moderate blood sugar levels preferring to release insulin in a something or nothing kind of way. So researchers believe that stem cells should be transformed to the entire cluster of islet cells with all cell types in order to be effective in controlling blood sugar levels.
Use of adult stem cells as possible precursors to islet cells
Currently, research is focused on several methods to isolate and cultivate stem cells or islet precursor cells. These could be from:
• From fetal cells
• From adult pancreatic tissue
Research is also focused on making insulin producing cells from embryonic stem cell lines.
Islet cells from fetal tissue
Fetal tissue has been found to be a good source of getting islet progenitor cells. These cultured islets are able to replicate and become functional islet tissues. But expanding these cultures of fetal islet progenitor cells was found to be difficult.
Islet cells from adult pancreatic tissue
Some researchers have used adult cadavers to culture islet cells. But it was found difficult to replicate and culture differentiated beta cells.
Researchers Fred Lavine at the University of California used human cadavers to produce islet cells. By adding specialized genes to the cells DNA these cells were made to replicate. Thus they established cell lines that could replicate in culture although they couldn't produce insulin. These cell lines were genetically engineered to make PDX-1 which is the beta islet cell gene which is necessary for the maturation of the beta cells.
These bioengineered cell lines could differentiate to insulin producing cells and could well turn out to be a future line of therapy. But the challenge is to make enough numbers of these cell lines that can produce sufficient quantities of insulin.
Islet cells from the cells of the pancreatic ducts
Research is focused on the fact that stem cells are found inter-mixed with mature differentiated duct cells.
Duct cells could be differentiated or reversed to a less mature type of cell. This can be converted to islet cell capable of making insulin. For instance, research conducted by Susan Bonner-Weir and associates have shown that ductal cells of pancreatic tissue could be differentiated into clusters of ductal and endocrine cells having the typical functional attributes of islet cell clusters with beta as well as non-beta cells. In other words, these islet cell clusters could produce more insulin when glucose levels were high and vice versa.
So in future duct cells could be removed from a diabetes patient say by biopsy, replicate these cells in culture and graft the cells back to the diabetes patient. Since type 1 diabetes people have malfunctioning beta cells this would work well for them. But of course autoimmune destruction has to be reckoned with. But type 2 diabetes people will have no such problem as they wouldn't need immunosuppressant therapy.
Bonner Weir's research has been substantiated by research conducted by Ammon Peck of the University of Florida. They have been successful in culturing pancreatic ductal epithelial cells of adult mice to clusters of islet cells that were effective in reversing diabetes when grafted on diabetic mice.
Insulin producing cells from embryonic stem cell lines
Theoretically a line of embryonic stem cells could be cultured and replicated to make pancreatic islet cells that could produce insulin. When embryonic stem cells are used to make islet cells the chances of autoimmune rejection is less. Promising results have been obtained in coaxing human embryonic cells into insulin-producing beta cells.
Evidence of human embryonic cells being capable of transforming into insulin producing cells have been advanced by research conducted by Melton Nissim Benvinisty of Hebrew University
These research efforts focused on transforming embryonic cells in culture to embryonic stem cell clumps or embryoid bodies that comprised cell types from all three germ layers. These embrryoid bodies were treated with nerve growth factors and other growth factors resulting in expression of PDX-1 gene. As PDX-1 is related to beta islet cell maturation the experiment was deemed successful. The cells in these embryoid bodies also produced glut-2 and glucokinase which are important for the secretion of insulin and better functioning of beta cells.
This means that human embryonic stem cells could be made to differentiate into insulin producing islets. Nevertheless type 1 diabetes is surely difficult to cure. That is because the human body's own immune system is responsible for cell destruction. But if embryonic cells were used to express the gene responsible for insulin transcription then the chances of being detected by the immune system is less.
Some researchers have suggested another interesting method. The islet cells obtained from islet stem or progenitor cells could perhaps be microencapsulated in a suitable material so that only insulin could pass through it but disallow possible interaction between cells of the immune system and the islet cells. In other words, these islet cells could continue secreting insulin without being destroyed by the immune system.
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