INTERNAL MEDECINE JOURNAL OF VIETNAM|NO 22/2021
26
CLINICAL RESEARCH
CHANGES OF CLINICAL CHARACTERISTICS IN PATIENTS
AFTER ALLOGENEIC UMBILICAL CORD-DERIVED
MESENCHYMAL STEM CELL TRANSPLANTATION
Ta Ba Thang1, Dang Thi Ngoc Quynh1, Dao Ngoc Bang1
Bach Quoc Tuan1, Nguyen Van Dung1
1Respiratory center, Military Hospital 103, Military Medical University
ABSTRACT
Objectives: To evaluate the changes of clinical and paraclinical characteristics in chronic obstructive pulmonary
disease patients after treatment of umbilical cord-derived mesenchymal stem cells. Subjects and method: 21
stable COPD patients were enrolled with C and D groups in accordance with GOLD 2018. Patients have infused
intravenously allogeneic umbilical cord-derived mesenchymal stem cells with a dosage of 1.5 X 106 MSCs
per kilogram of weight every 6 months for 6 months. Patients were followed every 3 months for 6 months:
clinical symptoms, quality-of-life (CAT), mMRC, 6-minute walking test (6MWT), some exacerbations, CRP, lung
function test, and arterial blood gas. Results: After 3 months, the decrease of CAT scores, mMRC, and rate
of exacerbations in group 1 were better than that of group 2. The rate of exacerbations gradually decreased
after 1, 3, and 6 months of MSCs transplantation. Lung function had no significant change after MSCs
transplantation. Conclusions: Allogeneic MSCs administration has initially improved symptoms, quality of life,
exercise tolerance, and reduced exacerbations in COPD patients with C and D groups.
* Keywords: Allogeneic umbilical cord derived mesenchymal stem cell; Chronic obstructive pulmonary disease.
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a
global burden of disease with high mortality, affecting
more than 380 million people worldwide. Current
therapies include pharmacological treatment and
non-pharmacological treatment [1, 4, 5]. However,
studies showed that recent therapies have limited
efficacy in reducing exacerbations and improving
lung function as well as in reducing mortality. Some
studies initially showed that stem cell transplantation
and lung regeneration that may be capable of
restoring pulmonary function and structures is a
potential treatment therapy in the future [2, 3, 6, 7. In
Vietnam, some hospitals have applied MSCs stem
cell transplantation in the treatment of COPD patients.
From 2018, Vietnam Military Medical University -
Military Hospital 103 applied allogeneic umbilical
cord-derived MSCs in the treatment of COPD. This
study was performed with the aim: to assess changes
in clinical and subclinical characteristics in patients
with the chronic obstructive pulmonary disease after
allogeneic umbilical cord-derived mesenchymal stem
cell transplantation.
SUBJECTS AND METHODS
1. Subjects
Including 36 patients were diagnosed with stable
COPD in groups C and D, treated in the Respiratory
Center, Military Hospital 103 from July 2018 to
March 2019, and were divided into 2 groups:
Corresponding author: Ta Ba Thang (tabathang@yahoo.com)
Date received: 06/5/2021
Date accepted: 28/5/2021
INTERNAL MEDECINE JOURNAL OF VIETNAM|NO 22/2021
27
CLINICAL RESEARCH
- Group transplanted MSCs (Group 1): Including 21
patients who underwent allogeneic umbilical cord-
derived mesenchymal stem cell transplantation
and internal treatment.
- Control group (Group 2): Including 15 patients
who only underwent internal treatment.
Inclusive criteria: patients have diagnostic criteria
of COPD, stable COPD, group C, D based on the
standard of GOLD (2018) [11].
*
Exclusive criteria: Current smokers or recently
quit smoking in less than 6 months. Comorbidities:
cardiovascular diseases (heart failure with left
ventricular ejection fraction ≤ 40%, heart valve diseases,
cardiomyopathy, severe arrhythmias or congenital
heart disease...), renal failure, hepatitis, hematological
diseases, cancers... Currently, participate in other
studies which use the same drugs. For group 1: use of
any TNF inhibitor within 3 months of screening visit; use
of an immunosuppressive medication (azathioprine,
methotrexate) that has not been at a stable dose for
at least 8 weeks prior to screening; evidence of active
malignancy or prior history of active malignancy that
has not been in remission for at least 5 years [9, 10].
2. Methods
* Study design: A prospective-randomized
controlled longitudinal trial.
Patients were examined clinically and performed
paraclinical tests (chest X-ray, lung function,
Arterial blood gas, serum CRP…) at times: before
transplantation of stem cells, 1 month, 3 months,
and 6 months after transplantation of stem cells.
Infuse the stem cells mixture to the patient: allogeneic
umbilical cord-derived mesenchymal stem cells
with the amount of 1.5 million mesenchymal stem
cells per kilogram of body weight. All patients in
this study were treated following to Guidelines of
the Ministry of Health about the internal treatment
of stable COPD (2018) [11].
Assess the changes of clinical and subclinical
characteristics in patients compared control
group at times: before transplantation of stem
cells, 1 month, 3 months, and 6 months after
transplantation of stem cells.
Management and analysis of the data by the SPSS
20.0 program.
RESULTS
Table 1: General characteristics of patients.
Parameters Group 1 (n = 21) Group 2 (n = 15) p Total (n = 36)
Age ( ± SD) 68.05 ± 6.56 (59 - 80) 65 ± 6.82 (54 - 76) > 0.05 66.78 ± 6.75 (54 - 80)
Male n (%) 19 (90.48) 15 (100) > 0.05 34 (94.44%)
Female n (%) 2 (9.52) 0 > 0.05 2 (5.56%)
Duration of disease (± SD) 12.76 ± 6.16 8.4 ± 7.72 > 0.05 10.94 ± 7.09
BMI (kg/m²) 21.23 ± 3.37
(14.32 - 27.34)
17.06 ± 2.81
(11.29 - 22.31) < 0.01 19.5 ± 3.74
(11.29 - 27.34)
CAT (score) 15.81 ± 6.5 (8 - 26) 19.4 ± 3.36 (14 - 24) > 0.05 17.31 ± 5.65 (8 - 26)
SMWD (meter) 304.67 ± 66.43
(205 - 428)
297.67 ± 67.69
(200 - 400) > 0.05 301.75 ± 66.08
(200 - 428)
mMRC (score) 1.86 ± 0.79 (1 - 3) 2.33 ± 0.9 (1 - 3) > 0.05 2.06 ± 0.86 (1 - 3)
Number of exacerbations
per year (time) 2.95 ± 1.4 (1 - 6) 2.73 ± 1.16 (1 - 5) > 0.05 2.86 ± 1.29 (1 - 6)
Group C 8 (38.1%) 0 < 0.05 8 (22.22%)
D 13 (61.9%) 15 (100%) < 0.05 28 (77.78%)
INTERNAL MEDECINE JOURNAL OF VIETNAM|NO 22/2021
28
CLINICAL RESEARCH
Patients in 2 groups were mainly males, accounting for 94.44%. The average age of patients was 66.78 ±
6.75 years. There was no difference in age and gender between 2 groups (p > 0.05). The mean duration of
disease was 10.94 ± 7.09 years, with an average BMI at the normal level, which was 19.5 ± 3.74 kg/m2. The
mean of six-minute walk distance was short (301.75 ± 66.08 meters). The average number of exacerbations
in one year was 2.86 ± 1.29 times. The average CAT and mMRC scores were high (17.31 ± 5.65 and 2.06
± 0.86 points, respectively). 22.22% of total patients were in group C, and 77.78% of total patients were in
group D. Group 1 had the high averages of CAT and mMRC scores (15.81 ± 6.5 and 1.86 ± 0.79 points,
respectively) and a short six-minute walk distance (304.67 ± 66.43 meters). There was no difference in CAT
score, SMWD, mMRC score ,and a number of exacerbations per year between 2 groups (p > 0.05).
Table 2: Compare changes of BMI, CAT score, mMRC score and SMWD after 3 months between 2 groups.
Parameters
( ± SD)
Group 1 (n = 21) Group 2 (n = 15)
T0 (1) T3 (2) T0 (3) T3 (4)
BMI (kg/m2)21.23 ± 3.37 21.55 ± 3.08 17.06 ± 2.81 17.03± 2.79
p p4,2 < 0.01
Change 0.31 ± 0.79 -0.03 ± 0.13
p> 0.05
CAT (score) 15.81 ± 6.5 13.43 ± 4.6 19.4 ± 3.35 20.93± 4.83
p p4,2 < 0.01
Change -2.38 ± 2.6 1.53 ± 3.0
p< 0.01
Decreased ≥ 2 scores 11 (52.38%) 2 (13.33%)
p< 0.05
SMWD (score) 304.67 ± 66.43 304.71 ± 69.09 297.67 ± 67.69 298.8± 68.11
p p2,1 > 0.05; p4,2 > 0.05; p3,1 > 0.05; p4,3 > 0.05
Change 0.05 ± 7.44 1.13 ± 5.88
p> 0.05
mMRC (score) 1.86 ± 0.79 1.29 ± 0.56 2.33 ± 0.9 2.47 ± 0.74
p P4,2 < 0.01
Change -0.57 ± 0.51 0.14 ± 0.52
p< 0.01
After 3 months, the mean of CAT scores and mMRC of group 1 decreased statistically significantly (p < 0.01);
there were no statistically significant differences in changes of SMWD and BMI between 2 groups (p > 0.05).
Chart 1: Compare the rate of exacerbations after 3 months between 2 groups.
INTERNAL MEDECINE JOURNAL OF VIETNAM|NO 22/2021
29
CLINICAL RESEARCH
After 3 months, the rate of exacerbations in group 1 was 19.05% (4/21 patients), in group 2 was 33.33%
(5/15 patients). This difference was statistically significant (p < 0.05). The rate of exacerbations after 3
months of group 1 was significantly lower than that of group 2 (p < 0.05).
Table 3: Compare changes of spirometry parameters after 3 months between 2 groups.
Parameters
T0 (1)
Group 1 (n = 21) Group 2 (n = 15)
T3 (2) T0 (3) T3 (4)
FVC
(%pred)
± SD 69.19 ± 15.05 64.57 ± 18.83 68.53 ± 13.37 69.07 ± 15.31
p p2,1 > 0.05; p2,4 > 0.05; p3,1 > 0.05; p4,3 > 0.05
Change -4.62 ± 16.1 0.53 ± 19.01
p> 0.05
FEV1
(%pred)
± SD 40.17 ± 14.33 33.75 ± 10.57 33.73 ± 10.71 30.47 ± 7.7
p p2,1 < 0.01; p2,4 > 0.05; p3,1 > 0.05; p4,3 > 0.05
Change -6.42 ± 10.2 -3.27 ± 8.22
p> 0.05
There was no difference in mean and change level of FVC, FEV1 between 2 groups after 3 months of
follow up (p > 0.05).
Table 4: Compare changes of ABG parameters after 3 months between 2 groups.
Parameters
T1 (1)
Group 1 (n = 21) Group 2 (n = 15)
T3 (2) T1 (3) T3 (4)
PaO2
(mmHg)
± SD 73.19 ± 14.87 74.8 ± 17.38 79.13 ± 17.1 76.73 ± 15.02
p p2,1 > 0.05; p2,4 > 0.05; p3,1 > 0.05; p4,3 > 0.05
Change 1.61 ± 23.24 -2.4 ± 8.4
p> 0.05
PaCO2
(mmHg)
± SD 45.14 ± 4.82 44.67 ± 5.13 45.0 ± 12.25 41.4 ± 11.69
p p2,1 > 0.05; p2,4 > 0.05; p3,1 > 0.05; p4,3 > 0.05
Change -0.47 ± 4.88 -3.6 ± 9.02
p> 0.05
SaO2
(%)
± SD 92.52 ± 5.99 92.76 ± 7.19 93.27 ± 8.38 93.67 ± 5.39
p p2,1 > 0.05; p2,4 > 0.05; p3,1 > 0.05; p4,3 > 0.05
Change 0.24 ± 10.17 -0.4 ± 3.94
p > 0.05
There was no difference in mean and change level of PaO2, PaCO2, and SaO2 between 2 groups after 3
months of follow up (p > 0.05).
INTERNAL MEDECINE JOURNAL OF VIETNAM|NO 22/2021
30
CLINICAL RESEARCH
DISCUSSION
1. General characteristics of patients
In our result shows that the mean age of studied
patients was 66.78 ± 6.75 years, of which 94.44%
of patients were males, only 5.56% (2/36BN) were
females. This feature is also consistent with previous
studies [1, 12, 13]. However, in studies in Europe
and America, the percentage of female patients is
higher. The average duration of disease of studied
patients was 10.94 ± 7.09 years, of which patients
had got COPD for 5 - 10 years, accounting for half.
The characteristics of the disease duration are
similar to those in Pham Kim Lien’s study (2012),
which had an average duration of disease of 11.52 ±
5.74 years. According to the results in table 3.4, the
studied patients had an average body mass index of
19.5 ± 3.74 kg/m2. This feature is similar to studies on
COPD in Vietnam. Characteristics of CAT, mMRC,
and SMWD of the studied patients showed that
COPD had affected the patient’s life. This feature
is similar to studies of Weiss D.J. et al. (2013) [12],
Ribeiro-Paes J.T. et al. (2011) [15]. In our study, the
majority belonged to group D (77.78%), 22.22% of
studied patients were in group C.
2. Changes in clinical characteristics
After MSCs transplantation, we found that patients
in group 1 greatly improved CAT score, mMRC
score, and rate of exacerbations after 1, 3, and 6
months of MSCs transplantation compared to pre-
treatment time. Changes in BMI and six-minute
walk distance were not statistically significant after
1, 3, and 6 months of MSCs transplantation. After
3 months, the mean of CAT score, mMRC score,
and rate of exacerbations of group 1 decreased
statistically significantly compared to group 2;
there were no statistically significant differences
in changes of SMWD and BMI between 2 groups.
Our study results have some similarities as well as
some differences compared with other studies on
stem cell transplantation for COPD patients in the
world. Research results of Ribeiro-Paes J.T. et al.
(2011) [15] or Stessuk et al. (2013) in stage 4 COPD
patients showed that all 4 patients had a slight
improvement in quality of life as well as more stable
clinical status. The total time without oxygen supply
through the nasal catheter is longer, in addition to
the exercise tolerance was higher, and reduction in
SaO2 during exercise was not significant.
Shortness of breath is a common symptom in COPD
patients, which can be quantified on the mMRC scale.
On the other hand, based on mMRC scale, it can be
used to compare results between studies directly. At
the same time, CAT is a questionnaire developed by
many international experts experienced in drafting
tools and questions in patient interviews, helping to
evaluate the most significant impact of COPD on the
health and daily life of patients. In addition, CODP
exacerbation is a common medical emergency. The
frequency of hospitalization and mortality due to
CODP exacerbation in our country is still high, causing
an economic burden for both their families and society.
Exacerbation frequency is a predictor of the risk of
exacerbations in the future. The improvement in CAT
score, mMRC score, and the rate of exacerbations
in group 1 showed that UCMSCs transplantation
effectively improved symptoms, reduced the risk of
exacerbations, and improved the quality of life for
COPD patients GOLD (2018) proposed.
3. Changes of paraclinical characteristics
At follow-up times of 1, 3, and 6 months, the mean
of spirometry parameters of group 1 changed
insignificantly after 1, 3, and 6 months of MSCs
transplantation (p > 0.05). There was no difference
in mean and change level of FVC, FEV1 between
2 groups after 3 months of follow-up (p > 0.05).
This feature is similar to the results of previous
stem cell studies. After stem cell transplantation,
COPD patients have modest improvement or no
improvement in spirometry parameters. Research
by Weiss D.J. et al. (2013) showed no statistically
significant differences in FVC and FEV1 over 2
years of follow-up and found no difference in FVC,
FEV1, total lung capacity, or total lung capacity
diffuse carbon monoxide capacity between MSCs
transplantation group and the control group. Results
indicated that stem cell therapy did not show a