Autologous Mesenchymal Stem Cell Transplant in Patients
with Type 1 Diabetes Mellitus
Olga Ulyanova,1 Manarbek Askarov,2 Larissa Kozina,3 Temirlan Karibekov,4
Galiya Shaimardanova,5 Aigerim Zhakupova,2 Diana Danilova,1
Dina Serebrennikova1
Abstract
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 significantly 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
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
E-mail: olgaulyanova1971@gmail.com
Experimental and Clinical Transplantation (2019) 1: 236-238
Copyright © Başkent University 2019
Printed in Turkey. All Rights Reserved.
Introduction
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
-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 autologous mesenchymal stem cells in animals and in patients with type 1
DM.9
Thus, autologous mesenchymal stem cell transplant (AMSCT) has attached attention as a potentially effective therapeutic approach for regeneration
of islet cells and treatment of type 1 DM.
DOI: 10.6002/ect.MESOT2018.P100
Olga Ulyanova et al/Experimental and Clinical Transplantation (2019) 1: 236-238
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 assessments 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.
Results
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.
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
Daily insulin, U
P value
Leptin, ng/mL
P value
HbA1c, %
P value
Baseline
Level
Level After
1 Month
Level After
2 Months
Level After
3 Months
63 ± 8.83
50.2 ± 12.1
.064
8.31 ± 2.03
> .05
8.44 ± 1.03
.41
57.5 ± 13.8
.73
12.67 ± 5.37
.056
8.27 ± 1.13
.29
53.6 ± 12.01
.42
10.77 ± 1.78
.016
8.74 ± 1.35
.84
6.86 ± 1.89
9.11 ± 1.46
Abbreviations: HbA1c, glycated hemoglobin
237
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 significantly higher than baseline mean leptin levels, at
6.86 ± 1.89 versus 10.77 ± 1.78 ng/mL (P = .016).
Discussion
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
238
Olga Ulyanova et al/Experimental and Clinical Transplantation (2019) 1: 236-238
AMSCT procedure in our study may indicate the
efficacy of AMSCT.
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