Time points | D29 | D62 | ||||||
---|---|---|---|---|---|---|---|---|
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 | 9 | 10 | 10 | 5 | 5 | 5 | 5 |
Organ coefficients (%) | ||||||||
 Brain | 0.8296 ± 0.0347 | 0.7953 ± 0.0725 | 0.8141 ± 0.0535 | 0.8264 ± 0.0508 | 0.7460 ± 0.0248 | 0.7861 ± 0.0549 | 0.7774 ± 0.0175 | 0.7628 ± 0.0700 |
 Heart | 0.3834 ± 0.0252 | 0.3881 ± 0.0328 | 0.3801 ± 0.0317 | 0.3766 ± 0.0210 | 0.3846 ± 0.0212 | 0.3864 ± 0.0489 | 0.3497 ± 0.0195 | 0.3706 ± 0.0217 |
 Liver | 2.9306 ± 0.1916 | 3.0058 ± 0.3383 | 3.0678 ± 0.2861 | 2.9715 ± 0.1706 | 2.9334 ± 0.1904 | 2.8800 ± 0.1623 | 2.8182 ± 0.2112 | 2.6826 ± 0.1439 |
 Spleen | 0.2192 ± 0.0092 | 0.2059 ± 0.0223 | 0.2152 ± 0.0162 | 0.2209 ± 0.0247 | 0.1995 ± 0.0116 | 0.1945 ± 0.0158 | 0.1739 ± 0.0162* | 0.1771 ± 0.0150 |
 Kidney | 0.7123 ± 0.0471 | 0.6869 ± 0.0508 | 0.7632 ± 0.0699 | 0.7507 ± 0.0461 | 0.7173 ± 0.1032 | 0.6875 ± 0.0681 | 0.7036 ± 0.0714 | 0.7139 ± 0.0287 |
 Thymus | 0.1385 ± 0.0285 | 0.1201 ± 0.0272 | 0.1529 ± 0.0301 | 0.1693 ± 0.0249* | 0.1138 ± 0.0305 | 0.1254 ± 0.0373 | 0.0742 ± 0.0051* | 0.1268 ± 0.0214 |
 Uterus | 0.2856 ± 0.0755 | 0.3026 ± 0.1076 | 0.2543 ± 0.0457 | 0.2763 ± 0.0829 | 0.3313 ± 0.1282 | 0.2914 ± 0.0676 | 0.2425 ± 0.0527 | 0.2387 ± 0.0295 |
 Ovary and oviduct | 0.0521 ± 0.0070 | 0.0483 ± 0.0102 | 0.0531 ± 0.0084 | 0.0601 ± 0.0118 | 0.0501 ± 0.0063 | 0.0548 ± 0.0052 | 0.0492 ± 0.0098 | 0.053 ± 0.0037 |
 Adrenal gland | 0.0291 ± 0.0040 | 0.0272 ± 0.0046 | 0.0269 ± 0.0044 | 0.028 ± 0.0057 | 0.0272 ± 0.0059 | 0.0245 ± 0.0032 | 0.0261 ± 0.0065 | 0.0238 ± 0.0039 |
 Thyroid and parathyroid glands | 0.0102 ± 0.0025 | 0.0088 ± 0.0039 | 0.0099 ± 0.0025 | 0.0109 ± 0.0036 | 0.0113 ± 0.0034 | 0.0112 ± 0.0027 | 0.0101 ± 0.0020 | 0.0145 ± 0.0023 |
Hematology and coagulation indicators | ||||||||
 RBC (× 106/μL) | 7.484 ± 0.276 | 7.691 ± 0.275 | 7.376 ± 0.306 | 7.467 ± 0.444 | 7.840 ± 0.413 | 7.828 ± 0.081 | 8.126 ± 0.13 | 8.122 ± 0.212 |
 Hemoglobin (g/dL) | 14.03 ± 0.46 | 14.42 ± 0.48 | 13.81 ± 0.54 | 14.03 ± 0.69 | 14.58 ± 0.46 | 14.62 ± 0.19 | 14.92 ± 0.53 | 15.28 ± 0.36 |
 Hematocrit | 44.14 ± 1.49 | 45.87 ± 1.58 | 43.65 ± 1.97 | 44.13 ± 2.05 | 44.84 ± 1.75 | 45.30 ± 0.97 | 46.64 ± 2.40 | 46.70 ± 1.05 |
 WBC (× 103/μL) | 6.058 ± 1.189 | 6.023 ± 1.535 | 6.417 ± 1.512 | 6.194 ± 1.856 | 5.168 ± 1.624 | 5.114 ± 2.530 | 4.056 ± 1.393 | 4.330 ± 1.322 |
 NEU% | 13.03 ± 6.57 | 13.28 ± 4.69 | 15.39 ± 7.28 | 12.77 ± 2.46 | 10.38 ± 4.55 | 9.60 ± 4.56 | 12.98 ± 2.28 | 15.42 ± 2.69 |
 LYM% | 83.88 ± 7.06 | 84.42 ± 4.67 | 82.04 ± 7.80 | 84.76 ± 2.62 | 87.42 ± 4.93 | 87.84 ± 5.52 | 84.76 ± 2.13 | 81.22 ± 2.88 |
 MON% | 1.12 ± 0.39 | 0.87 ± 0.29 | 1.08 ± 0.38 | 0.86 ± 0.21 | 0.98 ± 0.33 | 1.10 ± 0.74 | 0.76 ± 0.13 | 1.66 ± 0.83 |
 EOS% | 0.32 ± 0.21 | 0.26 ± 0.29 | 0.18 ± 0.14 | 0.22 ± 0.25 | 0.08 ± 0.08 | 0.14 ± 0.05 | 0.18 ± 0.08 | 0.24 ± 0.09* |
 BAS% | 0.20 ± 0.09 | 0.20 ± 0.07 | 0.21 ± 0.03 | 0.26 ± 0.05 | 0.26 ± 0.05 | 0.18 ± 0.08 | 0.20 ± 0.00 | 0.20 ± 0.10 |
 LUC% | 1.46 ± 0.76 | 0.96 ± 0.21 | 1.08 ± 0.32 | 1.12 ± 0.27 | 0.86 ± 0.21 | 1.14 ± 0.39 | 1.08 ± 0.29 | 1.30 ± 0.20 |
Serum biochemical indicators | ||||||||
 ALT (U/L) | 36.5 ± 15.4 | 38.8 ± 27.5 | 36.6 ± 7.7 | 39.0 ± 10.3 | 29.2 ± 5.5 | 41.8 ± 23.6 | 28.6 ± 3.8 | 42.4 ± 25.2 |
 AST (U/L) | 118.7 ± 21.0 | 138.4 ± 61.1 | 121.1 ± 24.5 | 135.3 ± 32.1 | 89.0 ± 13.3 | 102.6 ± 35.2 | 93.2 ± 19.8 | 92.2 ± 22.0 |
 ALP (U/L) | 67.3 ± 18.2 | 64.4 ± 12.6 | 79.0 ± 29.8 | 76.4 ± 29.1 | 55.6 ± 18 | 51.2 ± 19.4 | 58.2 ± 22.9 | 48.8 ± 6.1 |
 CHOL (mmol/L) | 1.874 ± 0.360 | 1.852 ± 0.237 | 2.011 ± 0.475 | 1.775 ± 0.411 | 1.946 ± 0.175 | 1.928 ± 0.335 | 2.022 ± 0.474 | 1.828 ± 0.544 |
 TG (mmol/L) | 0.212 ± 0.051 | 0.190 ± 0.098 | 0.194 ± 0.065 | 0.156 ± 0.053 | 0.152 ± 0.049 | 0.162 ± 0.089 | 0.186 ± 0.111 | 0.152 ± 0.029 |
 GLU (mmol/L) | 9.459 ± 1.374 | 8.982 ± 2.278 | 9.121 ± 1.425 | 8.752 ± 1.629 | 8.500 ± 1.172 | 7.932 ± 0.919 | 7.762 ± 2.26 | 7.430 ± 0.409 |
 BUN (mmol/L) | 7.474 ± 0.856 | 7.298 ± 1.403 | 8.341 ± 1.817 | 8.398 ± 1.821 | 6.488 ± 1.757 | 6.834 ± 1.701 | 6.714 ± 0.817 | 6.482 ± 0.474 |
 CREA (mmol/L) | 31.1 ± 2.3 | 35.0 ± 4.9 | 31.1 ± 4.7 | 30.6 ± 3.5 | 34.2 ± 6.9 | 31.0 ± 3.2 | 32.4 ± 3.6 | 32.8 ± 1.3 |
 TP (g/L) | 63.25 ± 3.99 | 62.72 ± 2.03 | 63.24 ± 3.48 | 61.73 ± 4.34 | 65.78 ± 1.79 | 67.30 ± 5.55 | 66.36 ± 1.59 | 67.46 ± 2.78 |
 ALB (g/L) | 47.66 ± 3.94 | 47.47 ± 3.10 | 48.05 ± 3.01 | 46.78 ± 4.16 | 48.50 ± 2.56 | 51.68 ± 5.55 | 50.00 ± 3.43 | 52.42 ± 2.80 |
 GLO (g/L) | 15.59 ± 1.05 | 15.26 ± 1.86 | 15.19 ± 1.43 | 14.95 ± 1.13 | 17.28 ± 1.97 | 15.62 ± 0.92 | 16.36 ± 2.65 | 15.04 ± 2.00 |
Immune function | ||||||||
 CD3+ CD4+ (%) | 51.519 ± 5.794 | 45.657 ± 8.165 | 49.177 ± 5.166 | 49.549 ± 6.996 | 63.082 ± 5.461 | 59.988 ± 5.758 | 57.948 ± 8.959 | 67.652 ± 8.211 |
 CD3+ CD8+ (%) | 43.037 ± 6.221 | 48.732 ± 7.394 | 44.06 ± 4.015 | 45.13 ± 6.500 | 34.198 ± 5.178 | 36.796 ± 5.334 | 38.92 ± 8.382 | 30.022 ± 7.914 |
 CD3+ CD4+ /CD3+ CD8+  | 1.233 ± 0.284 | 0.976 ± 0.294 | 1.133 ± 0.217 | 1.136 ± 0.294 | 1.901 ± 0.470 | 1.676 ± 0.398 | 1.580 ± 0.536 | 2.496 ± 1.170 |
 CD161+ (%) | 0.475 ± 0.384 | 0.760 ± 0.606 | 0.345 ± 0.192 | 0.520 ± 0.193 | 0.070 ± 0.104 | 0.110 ± 0.108 | 0.100 ± 0.061 | 0.100 ± 0.087 |
 CD45RA+ (%) | 56.011 ± 5.617 | 58.576 ± 6.744 | 60.710 ± 4.446 | 54.780 ± 5.155 | 55.024 ± 5.113 | 53.080 ± 7.829 | 53.390 ± 9.754 | 47.620 ± 7.266 |
Test of BALF (N = 5) | ||||||||
 WBC (× 103 cells/μL) | 1.52 ± 0.96 | 1.55 ± 1.24 | 1.33 ± 0.79 | 0.94 ± 0.64 | 3.08 ± 1.65 | 2.00 ± 1.05 | 2.30 ± 0.74 | 1.88 ± 0.89 |
 NEU% | 17.32 ± 6.44 | 18.86 ± 7.66 | 17.10 ± 4.71 | 14.80 ± 4.03 | 19.80 ± 5.05 | 29.12 ± 5.68 | 27.50 ± 13.57 | 21.10 ± 5.48 |
 LYM% | 69.72 ± 11.07 | 63.22 ± 18.69 | 65.84 ± 5.33 | 74.54 ± 7.22 | 66.84 ± 7.10 | 54.04 ± 8.56 | 56.12 ± 15.11 | 64.84 ± 9.30 |
 MON% | 0.64 ± 0.50 | 1.34 ± 0.71 | 2.06 ± 2.56 | 0.48 ± 0.36 | 1.40 ± 0.64 | 2.12 ± 0.91 | 2.12 ± 0.74 | 1.76 ± 0.84 |
 EOS% | 1.30 ± 0.87 | 0.96 ± 0.88 | 1.02 ± 0.63 | 0.86 ± 0.59 | 0.72 ± 0.56 | 1.02 ± 0.62 | 0.30 ± 0.12 | 0.74 ± 0.32 |
 BAS% | 3.96 ± 2.23 | 4.02 ± 2.00 | 2.92 ± 1.52 | 2.70 ± 1.08 | 7.28 ± 11.48 | 4.16 ± 1.54 | 3.12 ± 0.44 | 3.54 ± 0.80 |
 LUC% | 10.64 ± 5.19 | 15.10 ± 12.39 | 13.70 ± 5.79 | 8.60 ± 4.07 | 10.52 ± 1.43 | 13.72 ± 5.17 | 13.94 ± 4.10 | 11.62 ± 4.38 |