Safety evaluation of human umbilical cord-mesenchymal stem cells in type 2 diabetes mellitus treatment: A phase 2 clinical trial

Table 1 Quality control standards of human umbilical cord-mesenchymal stem cells

Test	Final frozen product	Final infusion product
Visual inspection	NA	Absence of visible, particle
Morphology	Fibroblastic	NA
Viability	≥ 90%	≥ 85%
Cell count	(4.5-6.0) × 107	According to clinical needs
Pathogen tests
Sterility	Negative	Negative
Mycoplasma	Negative	Negative
Endotoxin	< 0.5 EU/mL	< 0.5 EU/mL
Cell surface markers
CD73	≥ 95%	-
CD90	≥ 95%	-
CD105	≥ 95%	-
CD29	≥ 95%	-
CD34	≤ 2%	-
CD45	≤ 2%	-
CD79a	≤ 2%	-
CD14	≤ 2%	-
HLA-DR	≤ 2%	-

Not available.

Table 2 Baseline characteristics of participants

Variable	All patients	Placebo group	hUC-MSC group	Z	P value
	n = 34	n = 10	n = 24
Sex					0.45
Male	28 (82.4)	8 (80.0)	20 (83.3)
Female	6 (17.6)	2 (20.0)	4 (16.7)
Age in yr	52 (45.5, 56.0)	49.0 (44.0, 58.5)	52.0 (46.0, 56.0)	-0.19	0.85
Duration of T2DM in yr	10.00 (4.00, 14.00)	7.00 (3.75, 11.75)	10.00 (4.50, 14.00)	-0.97	0.33
BMI in kg/m2	24.21 (23.34, 26.25)	23.72 (23.00, 26.25)	24.61 (23.25, 26.50)	-0.42	0.68
FPG in mmol/L	8.95 (8.13, 10.14)	8.82 (7.81, 9.97)	9.13 (8.18, 11.91)	-0.42	0.68
HbA1c as %	7.95 (7.40, 8.50)	8.00 (7.28, 8.35)	7.95 (7.45, 8.50)	-0.49	0.70

Data are presented as median (minimum, maximum) or number of cases (percentage). BMI: Body mass index; FPG: Fasting plasma glucose; HbA1c: Glycosylated hemoglobin; hUC-MSC: Human umbilical cord-mesenchymal stem cell; T2DM: Type 2 diabetes mellitus.

Table 3 Baseline laboratory tests of participants

Variable	Placebo group	hUC-MSC group	Z	P value
	n = 10	n = 24
Routine blood
WBC	6.48 (5.71, 8.17)	6.87 (5.52, 8.13)	-0.227	0.821
PLT	232.0 (199.5, 253.8)	214.0 (163.0, 258.3)	-0.718	0.473
RBC	5.15 (4.58, 5.46)	4.94 (4.79, 5.45)	-0.076	0.94
NEU	3.80 (2.95, 4.89)	4.20 (2.90, 5.15)	-0.189	0.850
L	2.21 (1.69, 2.44)	2.23 (1.96, 2.61)	-0.454	0.65
MONO	0.45 (0.34, 0.53)	0.36 (0.31, 0.44)	-1.192	0.233
NLR	1.89 (1.41, 2.36)	1.64 (1.43, 2.13)	-0.227	0.821
Liver function
ALT	21.00 (18.00, 31.25)	25.50 (16.50, 48.25)	-0.606	0.545
AST	20.50 (17.00, 23.00)	21.50 (18.00, 31.75)	-0.872	0.383
γ-GT	27.00 (20.75, 31.00)	34.50 (23.75, 52.00)	-1.703	0.089
TP	73.70 (68.88, 76.93)	71.70 (68.13, 76.78)	-0.529	0.597
GLB	29.25 (24.63, 30.98)	25.75 (23.93, 28.33)	-1.966	0.049
Renal function
Urea	6.51 (4.68, 7.23)	5.87 (5.38, 6.61)	-0.227	0.821
Cr	65.00 (58.00, 73.00)	67.00 (56.25, 81.00)	-0.227	0.82
eGFR	106.59 (97.44, 111.71)	104.52 (84.42, 111.99)	-0.454	0.65
Blood fat
TC	4.61 (4.06, 5.38)	3.95 (3.55, 5.40)	-1.247	0.212
TG	1.67 (1.20, 3.04)	1.87 (1.13, 2.79)	-0.094	0.925
LDL-C	2.91 (2.53, 3.29)	2.48 (2.12, 3.72)	-1.077	0.281
HDL-C	1.14 (0.91, 1.33)	1.12 (0.88, 1.46)	-0.019	0.985
Coagulation function
PT	12.25 (12.00, 12.78)	12.15 (12.00, 12.60)	-0.494	0.621
APTT	34.05 (32.68, 37.60)	34.10 (32.58, 35.45)	-0.284	0.777
TT	17.95 (17.45, 19.00)	18.00 (17.65, 18.90)	-0.265	0.791
FIB	2.95 (2.61, 3.53)	3.07 (2.29, 3.22)	-0.302	0.762
DD	0.22 (0.22, 0.26)	0.22 (0.22, 0.30)	-0.36	0.719
Infection screening
HBsAg	0.00 (0.00, 0.00)	0.00 (0.00, 20.31)	-1.081	0.28
HCV-Ab	0.05 (0.04, 0.06)	0.09 (0.04, 0.14)	-1.679	0.093
HIV-Ag/Ab	0.07 (0.06, 0.08)	0.06 (0.05, 0.08)	-0.731	0.465
TP-Ab	0.04 (0.02, 0.06)	0.04 (0.04, 0.05)	-0.776	0.438
Tumor marker
AFP	2.80 (2.20, 3.85)	1.95 (1.65, 3.10)	-1.494	0.135
CEA	1.85 (1.40, 3.50)	2.15 (1.58, 3.08)	-0.416	0.677
CA199	8.45 (5.20, 17.33)	5.55 (3.35, 15.90)	-0.643	0.52

γ-GT: Gamma-glutamyl transferase; AFP: Alpha-fetoprotein; ALT: Alanine transaminase; APTT: Activated partial thrombokinase time; AST: Aspartate aminotransferase; CA199: Carbohydrate antigen 199; CEA: Carcinoembryonic antigen; Cr: Serum creatinine; DD: D-dimer; eGFR: Estimated glomerular filtration rate; FIB: Fibrinogen; GLB: Immunoglobulin; HBsAg: Hepatitis B surface antigen; HCV-Ab: Antibodies against hepatitis C virus; HDL-C: High-density lipoprotein cholesterol; HIV-Ag/Ab: Combined detection of antigen and antibody of human immunodeficiency virus; hUC-MSC: Human umbilical cord mesenchymal stem cell; L: Lymphocyte absolute value; LDL-C: Low-density lipoprotein cholesterol; MONO: Monocyte absolute value; NEU: Neutrophil absolute value; NLR: Neutrophil-to-lymphocyte ratio; PLT: Platelets; PT: Prothrombin time; RBC: Red blood cell (erythrocyte); TC: Total cholesterol; TG: Triglycerides; TP: Total protein; TP-Ab: Specific antibody against Treponema pallidum; TT: Thrombin coagulation time; Urea: Urea nitrogen; WBC: White blood cell.