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Table 5 Effects of haMSC-EVs on male rats’ organ, hematology and coagulation, serum biochemistry and immune function

From: Manufacturing, quality control, and GLP-grade preclinical study of nebulized allogenic adipose mesenchymal stromal cells-derived extracellular vesicles

Time points

D62

D29

Groups

Control

haMSC-EVs-low

haMSC-EVs-medium

haMSC-EVs-high

Control

haMSC-EVs-low

haMSC-EVs-medium

haMSC-EVs-high

Number of animals

10

10

9

10

5

5

5

5

Organ coefficients (%)

 Brain

0.5845 ± 0.0297

0.5528 ± 0.0271

0.5615 ± 0.0511

0.5665 ± 0.0407

0.4459 ± 0.0295

0.4711 ± 0.0534

0.4672 ± 0.0594

0.486 ± 0.0353

 Heart

0.3709 ± 0.0244

0.3604 ± 0.0219

0.3767 ± 0.0172

0.3532 ± 0.0290

0.3244 ± 0.0209

0.331 ± 0.0326

0.3334 ± 0.0295

0.3502 ± 0.0250

 Liver

2.8533 ± 0.1564

2.7510 ± 0.1987

3.0338 ± 0.3085

2.8267 ± 0.2462

2.6246 ± 0.1780

2.6831 ± 0.2501

2.7879 ± 0.2925

2.7908 ± 0.2252

 Spleen

0.1837 ± 0.0154

0.1783 ± 0.0197

0.1923 ± 0.0212

0.1974 ± 0.0204

0.1516 ± 0.0116

0.1778 ± 0.0291

0.1607 ± 0.0203

0.1951 ± 0.0272*

 Kidney

0.7939 ± 0.0639

0.7225 ± 0.0455*

0.8023 ± 0.0657

0.7487 ± 0.0656

0.6467 ± 0.0623

0.6562 ± 0.0505

0.7117 ± 0.0174

0.7038 ± 0.0435

 Thymus

0.1535 ± 0.0358

0.1257 ± 0.0291

0.1346 ± 0.0484

0.1212 ± 0.0212

0.0706 ± 0.0161

0.0748 ± 0.0155

0.0905 ± 0.0046

0.0861 ± 0.0291

 Testicle

0.8909 ± 0.0575

0.8315 ± 0.0817

0.8606 ± 0.0570

0.8354 ± 0.0610

0.6977 ± 0.1045

0.7019 ± 0.0837

0.661 ± 0.0870

0.7406 ± 0.0390

 Epididymis

0.3104 ± 0.0337

0.2945 ± 0.0235

0.2968 ± 0.0282

0.2980 ± 0.0439

0.2808 ± 0.0547

0.2986 ± 0.0197

0.3170 ± 0.0527

0.2998 ± 0.0585

 Adrenal gland

0.0165 ± 0.0024

0.0163 ± 0.0028

0.0165 ± 0.0022

0.0157 ± 0.0033

0.0122 ± 0.0029

0.0130 ± 0.0025

0.0109 ± 0.0019

0.0136 ± 0.0027

 Thyroid and parathyroid glands

0.0099 ± 0.0026

0.0107 ± 0.0019

0.0122 ± 0.0039

0.0103 ± 0.0033

0.0122 ± 0.0031

0.0120 ± 0.0018

0.0096 ± 0.0026

0.0138 ± 0.0035

Hematology and coagulation indicators

 RBC (× 106/μL)

8.312 ± 0.313

8.164 ± 0.479

8.287 ± 0.317

8.039 ± 0.286

8.792 ± 0.308

8.454 ± 0.488

8.344 ± 0.477

8.454 ± 0.312

 Hemoglobin (g/dL)

16.18 ± 0.61

15.55 ± 0.73

15.88 ± 0.53

15.33 ± 0.45**

15.42 ± 0.83

15.34 ± 0.36

15.12 ± 0.65

15.62 ± 0.34

 Hematocrit

50.02 ± 1.23

48.97 ± 2.23

49.79 ± 1.85

48.34 ± 1.06

48.26 ± 2.88

47.60 ± 0.69

47.40 ± 2.18

48.92 ± 1.65

 WBC (× 103/μL)

9.532 ± 1.705

9.557 ± 1.411

9.331 ± 2.982

10.002 ± 3.081

7.522 ± 1.733

7.598 ± 1.401

6.588 ± 1.616

7.690 ± 1.384

 NEU%

10.74 ± 2.80

11.41 ± 4.50

11.12 ± 3.39

12.55 ± 4.71

12.78 ± 5.74

14.62 ± 6.73

15.10 ± 2.69

13.58 ± 1.70

 LYM%

85.00 ± 3.67

84.82 ± 5.36

85.68 ± 4.01

83.87 ± 5.03

84.30 ± 5.84

82.10 ± 6.96

82.04 ± 3.94

83.98 ± 1.65

 MON%

1.14 ± 0.33

1.02 ± 0.44

1.14 ± 0.45

0.99 ± 0.41

1.12 ± 0.18

1.24 ± 0.35

0.88 ± 0.22

0.96 ± 0.28

 EOS%

0.28 ± 0.17

0.30 ± 0.24

0.17 ± 0.07

0.29 ± 0.27

0.58 ± 0.46

0.56 ± 0.36

0.26 ± 0.09

0.18 ± 0.13

 BAS%

0.31 ± 0.10

0.33 ± 0.09

0.31 ± 0.09

0.32 ± 0.08

0.26 ± 0.11

0.22 ± 0.04

0.22 ± 0.04

0.22 ± 0.13

 LUC%

2.50 ± 1.81

2.15 ± 1.39

1.58 ± 0.78

2.01 ± 1.24

0.96 ± 0.09

1.24 ± 0.28

1.50 ± 1.54

1.14 ± 0.43

Serum biochemical indicators

 ALT (U/L)

33.7 ± 8.5

35.4 ± 6.7

33.4 ± 6.5

34.2 ± 7.9

32.8 ± 4

33.0 ± 3.4

33.0 ± 5.5

32.8 ± 3.3

 AST (U/L)

137.0 ± 32.3

154.6 ± 28.4

130.4 ± 26.6

120.0 ± 37.9

115.8 ± 22.1

108.6 ± 18.6

104.8 ± 22.4

95.8 ± 6.2

 ALP (U/L)

170.8 ± 29.5

161.5 ± 38.0

156.7 ± 42.1

148.0 ± 31.7

108.6 ± 17.0

113.2 ± 41.4

129.2 ± 14.4

125.0 ± 18.6

 CHOL (mmol/L)

1.722 ± 0.355

1.559 ± 0.307

1.682 ± 0.294

1.725 ± 0.250

1.624 ± 0.387

1.868 ± 0.405

1.610 ± 0.163

1.622 ± 0.163

 TG (mmol/L)

0.235 ± 0.051

0.260 ± 0.134

0.277 ± 0.126

0.273 ± 0.154

0.212 ± 0.050

0.156 ± 0.064

0.226 ± 0.112

0.170 ± 0.043

 GLU (mmol/L)

9.376 ± 1.785

9.064 ± 1.769

9.831 ± 1.693

9.841 ± 1.526

9.156 ± 1.538

8.314 ± 2.288

8.942 ± 1.736

8.262 ± 1.635

 BUN (mmol/L)

6.843 ± 1.017

6.332 ± 0.963

7.726 ± 1.488

7.254 ± 1.074

6.716 ± 1.575

6.488 ± 0.623

6.392 ± 0.428

5.762 ± 0.265

 CREA (mmol/L)

23.9 ± 2.1

24.8 ± 1.2

24.3 ± 2.7

24.6 ± 4.2

30.2 ± 3.8

27.0 ± 2.7

26.6 ± 2.3

25.6 ± 4.7

 TP (g/L)

58.30 ± 2.42

56.27 ± 2.79

57.66 ± 2.76

57.58 ± 0.80

62.50 ± 2.80

60.10 ± 2.10

59.34 ± 1.83

59.04 ± 3.28

 ALB (g/L)

42.87 ± 1.60

39.84 ± 2.17**

41.78 ± 1.99

41.28 ± 1.18

42.6 ± 1.83

42.08 ± 1.83

41.62 ± 1.38

41.38 ± 2.06

 GLO (g/L)

15.43 ± 1.49

16.43 ± 1.33

15.88 ± 1.50

16.30 ± 1.10

19.90 ± 1.63

18.02 ± 1.77

17.72 ± 1.53

17.66 ± 1.67

Immune function

 CD3+ CD4+ (%)

47.598 ± 8.136

54.128 ± 9.947

52.594 ± 6.782

51.909 ± 8.007

59.270 ± 1.568

61.938 ± 4.647

63.074 ± 8.953

60.318 ± 5.723

 CD3+ CD8+ (%)

47.080 ± 6.460

41.566 ± 10.609

41.521 ± 6.489

43.484 ± 7.287

38.466 ± 1.552

35.788 ± 4.737

34.844 ± 8.495

37.270 ± 5.105

 CD3+ CD4+ /CD3+ CD8+

1.057 ± 0.385

1.477 ± 0.778

1.326 ± 0.432

1.272 ± 0.527

1.544 ± 0.100

1.770 ± 0.373

1.972 ± 0.84

1.660 ± 0.385

 CD161+ (%)

0.520 ± 0.625

0.510 ± 0.631

0.489 ± 0.276

0.891 ± 0.997

0.130 ± 0.091

0.120 ± 0.045

0.200 ± 0.122

0.060 ± 0.042

 CD45RA+ (%)

59.875 ± 5.755

58.970 ± 4.948

59.283 ± 6.278

54.596 ± 9.137

54.670 ± 6.799

52.360 ± 5.548

51.290 ± 4.679

54.810 ± 7.242

Test of BALF (N = 5)

 WBC (× 103 cells/μL)

2.63 ± 1.95

1.25 ± 0.93

1.66 ± 0.49

2.82 ± 2.07

4.17 ± 2.42

3.45 ± 2.17

4.26 ± 3.13

3.76 ± 1.87

 NEU%

11.54 ± 3.82

19.44 ± 5.40*

9.84 ± 2.01

13.52 ± 3.58

19.60 ± 2.50

20.64 ± 5.58

21.52 ± 7.17

30.22 ± 5.50

 LYM%

81.14 ± 5.01

69.84 ± 7.64*

82.54 ± 4.26

79.02 ± 3.73

67.72 ± 4.22

66.82 ± 9.61

64.10 ± 10.69

50.50 ± 5.70**

 MON%

0.88 ± 0.23

0.96 ± 0.78

1.68 ± 1.32

0.72 ± 0.24

1.52 ± 0.55

1.9 ± 0.56

1.54 ± 0.61

1.90 ± 0.70

 EOS%

0.96 ± 0.5

0.66 ± 0.43

0.60 ± 0.38

0.86 ± 0.74

0.68 ± 0.27

0.82 ± 0.59

0.58 ± 0.26

0.54 ± 0.21

 BAS%

2.22 ± 1.30

2.72 ± 0.90

2.04 ± 0.93

2.18 ± 1.18

2.60 ± 1.13

2.84 ± 0.46

2.40 ± 1.01

3.06 ± 1.09

 LUC%

4.70 ± 2.76

8.22 ± 3.93

4.04 ± 0.97

4.98 ± 1.69

10.44 ± 2.19

9.86 ± 5.99

12.26 ± 3.97

16.46 ± 5.82

  1. Hematology and coagulation indicators: RBC, red blood cell count; WBC, white blood cell count; NEU%, percentage of neutrophils (%); LYM%, percentage of lymphocytes (%); MON%, percentage of monocytes (%); EOS%, percentage of eosinophils (%); BAS%, percentage of basophils (%); LUC%, percentage of large unclassified cells (%). Serum biochemical indicators:ALT, alanine aminotransferase; AST, aspartate transaminase; ALP, alkaline phosphatase; CHOL, total cholesterol; TG, triglyceride; GLU, glucose; BUN, blood urea nitrogen; CREA, creatinine; TP, total protein; ALB, albumin; GLO, Globulin. Data were expressed as mean±SD. * and ** indicate significantly changed after administration (* P ≤ 0.05, ** P ≤ 0.01)