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Role of regenerative medicine in curing Diabetic wounds

By Zaigham Abbas

Diabetes mellitus is a group of metabolic disorder characterized by hyperglycemic state which is associated with a number of complications including retinopathy, nephropathy neuropathy and delayed wound healing. There are three major types of diabetes which are classified as type I, type II and type III. Type I diabetes is also known as insulin dependent diabetes mellitus which is an autoimmune disease.

In normal process, increased sugar level in blood promotes the production of insulin. But in this autoimmune disease the body´s own cells attack and destroy the body insulin producing cells of pancreas, in return causing deficiency or unavailability of insulin producing cells. Due to which blood glucose level rises resulting in type I of diabetes whereas, type II diabetes mellitus is known as non insulin dependent diabetes mellitus.

A high proportion of people are being affected by this type of diabetes globally, especially linked with the epidemic of obesity. This type of diabetes arises from the resistance or relative deficiency of insulin that is a pancreatic ß-cell hormone. Insulin impairment and insulin resistance is the major core defects of causing the type II diabetes mellitus.

The third significant type is gestational diabetes mellitus (GDM) is the glucose intolerance detected first during the pregnancy. In this type, woman without any previous history of diabetes develops diabetes during her pregnancy. This type of diabetes is independent of insulin production as well as insulin persistence but women who develop GDM are more prone to develop the type II diabetes mellitus during their lives. This condition includes severe adverse outcomes that are mostly associated with neonatal metabolic disorders, fetal macrosomia, still births and many others.

Diabetes mellitus is one of the most prevalent disorders with an increasing incidence. Prevalence of diabetes mellitus is increased to 8.5% globally with standard mortality ratio of 4.5 in developed countries.  An IDF report in 2015 predicted that the number of diabetes affected adults worldwide will rise from 422 million in 2017 to 642 million in 2040. The Diabetes Prevalence Survey of Pakistan has revealed staggering 16.98% prevalence of diabetes as 35.3 million people of Pakistan are found diabetic.

The common symptoms of diabetes includes weight loss, fatigue,  increased thirst known as polydipsia, frequent urination known as polyuria ,increased appetite known as polyphagia, renal failure, foot ulcer, retinopathy including blurry vision or complete loss of vision, amputations, cardiovascular diseases and even sexual dysfunctions. Abnormal metabolism of lipoprotein and development of hypertension are also common in people with diabetes.

Delayed wound healing is one of the major obstacles associated with diabetics. The real stimulus of delayed wound healing in diabetes remains vague, yet it has been proved that a complex interaction between disease-specific intrinsic faults in blood supply, increased progression of matrix, and abnormal angiogenesis along with some extrinsic factors including infections and continued trauma are involved in failure of wound healing in  diabetic individuals. Diabetic foot ulcer affects 15% of the people having diabetes and it is engaged in 84% of all diabetes- lower legs amputations.  The preventive measures of diabetes includes healthy and balanced eating, moderate regular exercise, limit processed food, quit smoking and alcohol intake, manage body weight.

Most commonly used therapies for healing diabetic wound include use of antibiotics, surgical techniques that involve angioplasty, endoartereoctomy, grafting and several wound care products. But these therapies provided insufficient and short term treatment along with many associated side effects. With the advancement in research related to diabetes, the more efficient methods for healing of diabetic wound are introduced.

The current treatment modalities of curing diabetic wounds include use of bone marrow derived stem cells, negative pressure dressings, bioengineered skin transplant, growth factors therapies, hyperbaric oxygen treatment and chemical debridement techniques. Some important medicinal treatments include antiplatelets therapy, anticoagulant therapy and Low density cholesterol (LDL) lowering drugs.

 

In Pakistan, the widely used methods for the treatment of diabetic wounds include antibiotic therapy, surgery, off loading devices and wound care products. Moreover, In March 2006, Prof. Faisal Masud confirmed that the use of tincture iodine in one liter of 75% ethyl alcohol can heal the diabetic wound very efficiently.

In the supervision of Dr. Zaigham Abbas, immunology group MMG, University of the Punjab (PU), Ayesha Nawaz worked on a project entitled as “Evaluation of wound healing effect of stem cells derived conditioned media in normal and diabetic mice” with the collaboration of Mr. Shahbaz Aslam and his student Sana Saleem & Tahira Tayyaba of IBB, PU. The purpose of this study was to examine the potential of Adipose derived stem cells conditioned media (ADSC-CM) in diabetic wound healing. In this experimental work, the mice were induced with diabetes and excisional wounds. Afterwards they were treated with ADSC-conditioned media. All the parameters were checked to ensure the progression of the ailment and then the suppression of the disease with the applied current therapy. The mice treated with ADSC-conditioned media showed significant wound closure as well as reduction in blood glucose levels of mice. No side effects related to ADSC-CM were observed during this treatment in mice models and it provided a secure and safe diabetic wound healing. In the future the underlying molecular mechanisms of diabetic wound healing and reduced blood glucose levels of ADSC-CM will be explored. Moreover, the use of stem cells for skin regeneration will also be explored at the lab in future.

Dr. Zaigham Abbas

Assistant Professor at Department of Microbiology and Molecular Genetics, University of the Punjab Lahore.

Email: zaigham.mmg@pu.edu.pk

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