Objectives: Our goal was to determine the efficacy of autologous mesenchymal stem cell transplant for treatment in patients with type 1 diabetes mellitus.
Materials and Methods: We examined 5 patients (4 male, 1 female; age 20-42 y) with type 1 diabetes mellitus who received autologous mesenchymal stem cell transplant (cells were obtained from the patient’s iliac crest and cultured for 3-4 weeks) performed by intravenous infusion. The quantity of autologous mesenchymal stem cells infused was 95 to 97 × 106. We analyzed daily insulin dosages and leptin and glycated hemoglobin levels in patients before and 1, 2, and 3 months after their autologous mesenchymal stem cell transplant procedure.
Results: In patients with type 1 diabetes mellitus, autologous mesenchymal stem cell transplant led to a decrease in daily insulin dosage levels, from 63 ± 8.83 to 50.2 ± 12.1 U (P = .064) after 1 month, with signi-ficantly increased leptin levels and trend to decreased glycated hemoglobin levels, from 6.86 to 10.77 ng/mL (P = .016) and 9.11% to 8.74% (P = .84) after 3 months, respectively.
Conclusions: Daily insulin dosage level decreased within 1 month and leptin levels increased significantly within 3 months after autologous mesenchymal stem cell transplant in patients with type 1 diabetes mellitus.
Key words : Adipokines, Glycated hemoglobin, Pancreatic islet cell regeneration
Recently, diabetes mellitus (DM) has become one of the main public health care problems, with higher incidence worldwide. According to the International Diabetes Federation, by 2040, the number of patients with DM in the world will reach 642 million people.1 Diabetes mellitus is a major risk factor for ischemic heart disease and stroke, which collectively account for high rates of morbidity and mortality among adult patients. Type 1 DM is the result of the immune-mediated destruction of insulin-producing β-cells, which are located in the islets of Langerhans of the pancreas.2 The administration of exogenous insulin through daily injections or insulin pumps is the most prominent treatment for type 1 DM, but its administration is often associated with impaired glucose metabolism control, which ultimately leads to episodes of hyperglycemia or hypoglycemia.
Some other approaches have been developed in past decades, such as pancreas and islet transplantation.3,4 Immunosuppression toxicity, limited donor supply, and high procedural costs limit this therapy to patients with type 1 DM. Stem cells are a sufficient source for creating insulin-producing cells, such cells are derived from mesenchymal stem cells, embryonic stem cells, and induced pluripotent stem cells.5 Although progress in use of embryonic stem cells has been demonstrated, their application is limited due to ethical complications.6-8 Some studies have demonstrated treatment the efficiency with auto-logous mesenchy-mal stem cells in animals and in patients with type 1DM.9
Thus, autologous mesenchymal stem cell trans-plant (AMSCT) has attached attention as a poten-tially effective therapeutic approach for regeneration of islet cells and treatment of type 1 DM.
Materials and Methods
This prospective cohort study included 5 patients (20-42 years old) with type 1 DM who received AMSCT performed by intravenous infusion. We analyzed the daily insulin dosages, leptin levels, and glycated hemoglobin (HbA1c) levels in patients before and 1, 2, and 3 months after AMSCT. Autologous mesenchymal stem cells were obtained from bone marrow samples of the iliac crest of patients and were cultured for 3 to 4 weeks. For AMSCT, an intravenous infusion of 50 mL/hour was used. The quantity of autologous mesenchymal stem cells infused was 95 to 97 × 106. This clinical study and its methods were approved by the Local Ethics Committee following Helsinki Declaration guidelines at our institution. All the patients signed written informed consent forms before the recruitment.
Statistical analyses were performed using standard methods and Stastistica software (StatSoft Inc., version 6.0, Tulsa, OK, USA). Clinical assess-ments of patients, as described, were calculated using averages, margins of error, and standard deviations. To compare independent groups, we used the nonparametric Mann-Whitney U test.
Before the AMSCT procedure, all patients with type 1 DM had poor glycemic control. Among our patients, HbA1c level was more than 7%. We did not observe any complications after the AMSCT procedure.
In our examinations, we found that the mean baseline level of leptin in patients with type 1 DM was 6.86 ± 1.89 ng/mL, which is within the normal range. The mean baseline level of HbA1c was 9.11 ± 1.46 %, which is higher than the established normal level (Table 1). The mean daily insulin dosage level was 63.0 ± 8.83 U.
On the day of AMSCT, patients with type 1 DM were given subcutaneous insulin. Patient dose was adjusted according to their blood glucose level, which was checked once every 4 hours during the first day of AMSCT. During the subsequent 3 days, fasting glucose and postprandial glucose levels were throughly controlled.
Baseline data and their changes after AMSCT are presented in Table 1. In patients with type 1 DM, 1 month after the procedure, the mean daily insulin dosage level decreased from 63.0 ± 8.83 to 50.2 ± 12.1 U (P = .064) and the mean leptin and HbA1c levels did not change significantly, from 6.86 ± 1.89 to 8.31 ± 2.03 ng/mL (P > .05) and from 9.11 ± 1.46% to 8.44 ± 1.03%, respectively (P = .41) (Table 1).
2 months after AMSCT, corresponding mean daily insulin dosages, leptin levels, and HbA1c levels did not significantly change in patients with type 1 DM from baseline, with daily insulin dosage levels of 63.0 ± 8.83 versus 57.5 ± 13.8 U (P = .73), baseline versus 2-month leptin levels of 6.86 ± 1.89 versus 12.67 ± 5.37 ng/mL (P = .056), and baseline and HbA1c levels of 9.11 ± 1.46% versus 8.27 ± 1.13% (P = .29) (Table 1).
After 3 months, mean leptin levels in patients with type 1 DM who received AMSCT were signifi-cantly higher than baseline mean leptin levels, at 6.86 ± 1.89 versus 10.77 ± 1.78 ng/mL (P = .016).
Three months after AMSCT, patients with type 1 DM showed significantly increased leptin levels, with trend to decreased daily insulin dosages and HbA1c levels. Leptin is a peptide hormone secreted by fat cells that regulates the control of glucose homeostasis.10 Leptin may have clinical relevance for treatment of hyperglycemia, particularly in conditions of leptin deficiency, such as lipodystrophy and type 1 DM.11 Rodents and humans with type 1 DM and leptin deficiency demonstrated that leptin resistance affected glucose metabolism.10,11 According to some studies, leptin levels were also elevated after fetal stem cell transplant in patients with type 1 and type 2 DM.12,13 Autologous adipose-derived stem cells were also shown to be efficient in a study of patients with type 2 DM.14
The observed significant increase in leptin level and the tendency of decreased daily insulin dosage and HbA1c levels in patients who received the AMSCT procedure in our study may indicate the efficacy of AMSCT.
Volume : 17
Issue : 1
Pages : 236 - 238
DOI : 10.6002/ect.MESOT2018.P100
From the 1Department of Endocrine Disturbances, the 2Department of Stem Cell
Technology, the 3Department of Clinical Laboratory, the 4Deputy Chairman of the
Board for Medicine and Science, and the 5Department of the Research Management,
the National Scientific Medical Research Center, Astana, Kazakhstan
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Olga Ulyanova, Department of Endocrine Disturbances, National Scientific Medical Research Center, 010009, Ave. Abylay-khan #42, Astana, Kazakhstan
Phone: +7 70 138 38107
Table 1. Changes in Daily Insulin Dosages, Leptin Levels, and Glycated Hemoglobin Levels After Autologous Mesenchymal Stem Cell Transplant in 5 Patients with Type 1 Diabetes Mellitus