A Comparative Histological Study on the Role of Umbilical Cord Mesenchymal Stem Cells Versus Their Conditioned Medium on the Pancreatic Beta Cells in Experimentally Induced Diabetes Mellitus in Albino Rat

Abstract

Background: Diabetes Mellitus (D.M.) is a major health problem affecting more than 200 million worldwide. Type I diabetes mellitus (TIDM) is an autoimmune disease mediated by the destruction of β cells in the pancreas that has no definitive cure till present. Currently, regenerative medicine using umbilical cord blood derived mesenchymal stem cells (UCB-MSCs) offers promising treatment. Meanwhile, Conditioned medium (CM) shows effectiveness for medication of various diseases. Aim of the work is to compare the role of UCB-MSCs versus their CM alone on pancreatic beta cells in a rat model of Streptozotocin (STZ)-induced type I diabetes Mellitus. Material and Methods: Forty adult male albino rats were divided randomly into 4 groups; Group I (control group), Group ІІ (Diabetic group) which were injected (I.P) by a single dose of 1ml of STZ 35 mg/kg body weight and subdivided equally into Subgroup IIA and Subgroup IIB in which rats were sacrificed after 2 and 4 weeks respectively. Group III (Diabetic + UCB-MSCs) which were given STZ as in group II and each rat was injected with 1× 106 cells/ml of UC-MSCs into tail vein and subdivided equally into Subgroup IIIA and Subgroup IIIB in which rats were sacrificed after 2 and 4 weeks respectively. Group IV (Diabetic + CM) which were given STZ as in group II and the rats received a dose of 0.5 ml of CM that was injected intramuscularly once per week and subdivided equally into Subgroup IVA and Subgroup IVB in which rats were sacrificed after 2 and 4 weeks respectively. Pancreatic specimens were prepared for histological and immune-histochemical techniques. Morphometrical and statistical studies were done. Results: Group ІІ (Diabetic group) stained by H& E showed distortion of the architecture of islets of Langerhans and multiple injuries in cells of the islets including vacuolations in the cytoplasm and small and darkly stained nuclei. In addition, it resulted in decrease size of islets and appearance of many empty spaces within it. There was significant decrease in body weight, serum insulin and C-peptide level and also, in insulin immunohistochemical stained positive cells. Moreover, significant increase in blood glucose and in caspase-3 immunohistochemical stained positive cells was found. Group III (Diabetic + UCB-MSCs) and Group IV (Diabetic + CM) both showed an obvious histological and biochemical improvement when compared to Group II (Diabetic group). Conclusion: UCB-MSCs injection was more effective than injection of CM in the treatment of type I diabetes mellitus. However, CM represent a new modality of cell free therapies with broad application which need more investigations.