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 |