Diabetes Mellitus is a chronic disorder characterized by
hyperglycemia due to insulin deficiency or insulin resistance.
There is no permanent cure for Diabetes. Only way is to replace
insulin producing beta-cells. Whole pancreatic transplantation and
purified pancreatic islets transplantation are the answer to cure
for diabetes. But scarcity of suitable donor and morbidity, high
cost involved are limiting factors for pancreatic transplantation.
Islet cell transplantation is less invasive procedure and safer than
total pancreatic transplantation established in year 2000. Isolated
islets carry less antigenic property, need less immunosuppression
with fewer side effects. But major disadvantage is the life-long
commitment of immune suppression which is costly and has
side effects. High dose calcineurin inhibitor therapy worsens
nephropathy [1]. After the islet transplantation, the clinical
improvement in hyperglycemia lasts for 2 years. Subsequently,
the islet function declines. Unless more cells are transplanted,
euglycemia is not maintained. Patients eventually returns to full
insulin dependency [2,3].
Stem cells hold great promise to provide a ready source of
transplantable, insulin secreting tissues. Soria et al. [4] showed
that isolated beta-cells in the absence of other islet cells are less
responsive to changes in glucose concentration than intact islet
clusters made up of all islet cell types. Hence, stem or precursor cell
types can be cultured to produce all cells of islet clusters. The main
goal is not only insulin bio-synthesis but also its correct processing,
storage and regulator secretion in response to physiological signals.
Soft permeable coating has been developed to hide cells from the
immune system. This protect cell from an immune attack while
allowing them to sense glucose and secrete insulin in response
to hyperglycemia. Even if cells do not survive for a patient’s lifetime,
bio-degradable coatings will break down in the body, could
theoretically allow new cells to be transplanted without recovering
the build-up or removal of capsule skeleton. The most extensive
human trials were conducted in Moscow. The Auckland, New
Zealand company uses beads made up of alginate - a gel forming
polymer. They reported a trial involving 7 type-1 DM patients who
received transplants of alginate encapsulated, neonatal pig islet
cells. Present encapsulated strategies have yet to show efficient
performance of islets. Encapsulated stem cells derived therapies in
diabetes may ultimately work.
e. Adult stem cells from bone-marrow and from umbilical cord
e. Adult stem cells from bone-marrow and from umbilical cord
Stem cell therapy implies the replacement of diseased or
lost cells from progeny of pluripotent or multi-potent cells. Both
embryonic stem cells (derived from inner cell mass of a blastocyte)
and adult stem cells have been used to generate surrogate beta
cells. There is failure in trans-differential into pancreatic beta
cells after transplantation of bone-marrow cells in mice. Finding
the right way to protect cells and intellectual property will be key
for getting cell therapy to patients. Human Embryonic Stem Cells
when differentiated into beta cells do not respond correctly to cues
in the blood stream i.e. not property responding to glucose level.
Transplanting less mature cells into mice showed improvement in
diabetes, but tumors developed in 5% of the treated mice suggesting
that some of the pro generator cells never stopped dividing. At the
moment encapsulation is the only way to ensure prevention of
tumors and autoimmune attack.
In autologous stem cell therapy, the stem cells are given into
pancreatic artery via catheter. Patient who cannot safely undergo
catheterization procedure may elect to receive the stem cells
intravenously. Overall improvement reported in studies included
more stable blood glucose, lower fasting blood sugar, decreased
leg pain, lower B.P. and absence of hypoglycemia. In 25%, there
was improvement in erectile function. On stem cell therapy, there is lot of hope and it seems that we are almost near the goal of curing
diabetes. But still, there are many hurdles to overcome. May be
in the next decade this will become a primary mode of therapy for
Diabetes Mellitus.