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Bone Marrow Stem Cells Toward Reversing Type-1 Diabetes

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Eating what we want and when we want is a guilty pleasure for most of us, but it is a deadly choice for diabetics. Individuals diagnosed with Type-1 diabetes are perpetually dependent on insulin injections after each meal to suppress elevated levels of blood glucose, a condition referred to as hyperglycemia. If left unmanaged, sustained hyperglycemia will erode nerves and blood vessels resulting in catastrophic complications for organs systems requiring proper innervations and perfusion.

Currently, the standard treatment for Type-1 diabetes is insulin injections – a regiment that requires vigilance and precision. Diabetics have to measure the amount they eat and guess the correct dose of insulin relative to blood glucose levels. Too much insulin will cause a dangerous drop in blood glucose, and if not resolved immediately can lead to unconsciousness, coma, or even death. If too little insulin is given, circulating glucose will remain high, rendering the intervention inadequate to stave off the maladies of hyperglycemia. Managing insulin dependent diabetes is walking a tight rope between high and low blood sugar. Such perpetual fear is no way to live and far from a cure. Researchers and clinicians have shifted their attention to stem cells as a promising candidate to cure Type-1 diabetes.

Stem cells within the bone marrow have the ability to regenerate and protect insulin producing pancreatic cells. These cells that secrete insulin are referred to as β-cells. Individuals with Type-1 diabetes are unable to produce the necessary amount of insulin because their β-cells are under attack by the immune system. Typically, individuals become symptomatic when more than 80% of their β-cell population has been destroyed. At this point, the body is unable to produce adequate insulin to respond to rises in blood glucose.

One type of stem cell inside the bone marrow has received special attention because of its capacity to turn into a wide array of specialized cells. This is the mesenchymal stem cell (MSC). The potential for MSCs to turn into insulin producing β-cell was first observed in 2003 in an initial study by Ianus et al. Irradiated mice were injected with GFP (a fluorescent protein used to track cells) labeled bone marrow stem cells and after 6 weeks, GFP positive cells were found in the insulin producing region of the pancreas. In addition, these cells exhibited the characteristics of a competent β-cell and secreted insulin upon glucose stimulation.

In a subsequent study, Hess et al. first injected irradiated mice with streptozotocin (a β-cells toxin to produce experimental Type-1 diabetes) and then transplanted GFP labeled bone marrow stem cells. The results were similar to Choi et al with one exception. Although GFP cells were identified in the pancreas, there were only trace amounts that produced insulin—too few to have an observable control over high blood sugar. Despite the negligible replacement of β-cells, mice given bone marrow cell injections exhibited reduced blood glucose levels and increased insulin production, which is a change that was not observed in the control population. Researchers concluded that although the bone marrow cells did not adopt a β-cells phenotype, they improved upon the capacity of existing β-cells to produce insulin.

The phenomenon of bone marrow cells to promote β-cells regeneration without becoming insulin-producing cells was becoming apparent in all subsequent studies. Mathews et al. reported that endothelial progenitor cells (EPCs) – a constituent of the bone marrow cell population – improved the vascularization of β-cells, which is an essential aspect of tissue regeneration. Urban et al. suggested that MSCs of the bone marrow had immunosuppressive properties and contributed to the regeneration of β-cells by protecting them from destruction by the immune system (the underlining cause of Type 1 diabetes). As of now, one thing researchers agree on is bone marrow cells are capable of regenerating β-cells and reversing the symptoms of Type-1 diabetes—even though these cells do not directly turn into fully functional β-cells.

Evidence for the use of autologous bone marrow stem cells to treat Type 1 diabetes is rapidly emerging. Chief Endocrinologist at Beijing Tiantan Puhua, Qiong Zhang, has been treating diabetic patients for five years by administering bone marrow cells via IV. So far, 70 percent showed improved control over blood sugar and increased production of insulin. Included in this 70 percent, 30 percent of those who received treatment are completely off insulin medication. This is perhaps the first true therapy for Type 1 diabetes. Although it has yet to be recognized for its clinical value in the states, stem cells therapy is the most promising solution to this delicate and not so sweet condition.

Copyright © 2012 Alex Martin MD & Xin Zhang, Los Angeles

References:

  1. 1.    Ianus A, Holz GG, Theise ND, Hussain MA. In vivo derivation of glucose-competent pancreatic endocrine cells from bone marrow without evidence of cell fusion. J Clin Invest 2003; 111: 843– 850.
  2. 2.    Choi JB, Uchino H, Azuma K, Iwashita N, Tanaka Y, Mochizuki H et al. Little evidence of transdifferentiation of bone marrow- derived cells into pancreatic beta cells. Diabetologia 2003; 46: 1366–1374.
  3. 3.    Hess D, Li L, Martin M, Sakano S, Hill D, Strutt B et al. Bone marrow-derived stem cells initiate pancreatic regeneration. Nat Biotechnol 2003; 21: 763–770.
  4. 4.    Mathews V, Hanson PT, Ford E, Fujita J, Polonsky KS, Graubert TA. Recruitment of bone marrow-derived endothelial cells to sites of pancreatic beta-cell injury. Diabetes 2004; 53: 91–98.
  5. 5.    Urban VS, Kiss J, Kovacs J, Gocza E, Vas V, Monostori E et al. Mesenchymal stem cells cooperate with bone marrow cells in therapy of diabetes. Stem Cells 2008; 26: 244–253.

 

 

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