Table 1.
Preclinical in vivo studies assessing the immunomodulatory effect of MSC therapy in vascularized composite or skin allotransplantation.
| Authors | Animal (number) | Allogeneic transplant | MSC type | MSC dose (days of infusion) |
Other treatments (days of administration) |
Days of therapy-free follow-up | Increased graft survival in MSC alone? (P value) | Percent of grafts surviving until end point |
|---|---|---|---|---|---|---|---|---|
| Bartholomew et al. (2002) [23] | Baboon (8) | Skin | BMSC allogeneic |
20 × 106 cells/kg (0, 3) | None | Yes (unstated) | ||
|
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| Aksu et al. (2008) [24] | Rat (44) | Skin | BMSC allogeneic |
2-3 × 106 cells (0, 7, 14, 21) | TBI (1), CsA (0–20), BM IV (0, 7, 14, 28) |
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|
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| Sbano et al. (2008) [25] | Rat (62) | Skin | BMSC allogeneic |
5.7 × 106 cells/kg (0) 10.3 × 106 cells/kg (0) |
CsA (0–30) | No (<0.001) | ||
|
| ||||||||
| Pan et al. (2010) [26] | Rat (47) | Hind-limb | BMSC allogeneic |
200 × 106 cells (−30) | TBI (−30), RAPA (−30–100), ALG (−6, −4, −2), BMT (−30) | 0† | Yes (unstated) | 100 |
|
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| Kuo et al. (2009) [27] | Swine (23) | Hind-limb | BMSC allogeneic |
1 × 107 cells (−1, 3, 7, 14, 21) | TBI (−1), CsA (0–28) | 280 | Yes (0.02) | 60 |
|
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| Kuo et al. (2011) [28] | Swine (16) | Hind-limb | BMSC allogeneic |
1 × 107 cells (−1, 1, 3, 7, 14, 21) | TBI (−1), CsA (0–28) | 100 | Yes (0.018) | 67 |
|
| ||||||||
| Kuo et al. (2011) [29] | Rat (28–36) | Hind-limb | ASC allogeneic |
2 × 106 cells (7, 14, 21) | ALS (−4, 1), CsA (0–28) | 180 | 89 | |
|
| ||||||||
| Kuo et al. (2012) [30] | Swine (16) | Facial | BMSC allogeneic |
2.5 × 107 cells (−1, 1, 3, 7, 14, 21) | CsA (0–28) | 67†† | Yes (0.123) | 0 |
|
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| Larocca et al. (2013) [31] | Mouse (21) | Skin | ASC allogeneic |
5 × 105 cells (1) | BM IV | Yes§ (<0.05) | ||
|
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| Lee et al. (2014) [32] | Mouse (48) | Skin | ASC or CM human |
1 × 106 cells or 0.3 mL CM∗ (0) | None | Yes§§ (<0.005) | ||
|
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| Jeong et al. (2014) [33] | Rat (21) | Hind-limb | BMSC allogeneic |
1 × 105 cells (0, 1, 2, 3) | None | Yes (<0.001) | ||
|
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| Cheng et al. (2014) [34] | Rat (32) | Hind-limb | ASC syngeneic |
2 × 106 cells (1) | TBI (−1), ALG (−1, 10), CsA (0–10) | 140 | 67 | |
|
| ||||||||
| Ramirez et al. (2014) [35] | Rat (47) | Hind-limb and/or HAW | ASC syngeneic |
2 × 106 cells (1, 8, 15) | ALS (−1, 10), CsA (0–10) | 140 | 38 HLOMC, 0 HAW, 0 HLOMC + HAW |
|
|
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| Plock et al. (2015) [36] | Rat (35) | Hind-limb | BMSC or ASC allogeneic |
1 × 106 or 5 × 106 cells (1) | ALS (−4, 1), tacrolimus (0–20) | 100 | 46 BMSC, 47 ASC |
|
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| Davis et al. (2014) [37] | Mouse (38) | Skin | BMSC or ASC human |
5 × 105, 3 × 106 cells, respectively (7) | Anti-CD4/CD8 mAbs (0, 2, 5, 7, 14), busulfan (5) | Yes (unstated) | ||
|
| ||||||||
| Hivelin et al. (2016) [38] | Rat (24) | Hemifacial | BM, BMSC, D/RCC |
100 × 106, 5 × 106, 10 × 106 cells, respectively; intraosseous injections | Anti-αβ-TCR mAb, CsA (1–7) | Control: 25–29††, BMSC: 27–32†† |
Yes (0.03) | 0 |
↑: increased; ALG: antilymphocyte globulin; ALS: antilymphocyte serum; ASCs: adipose tissue-derived mesenchymal stem cells; BM: bone marrow; BMSC: bone marrow-derived mesenchymal stem cell; BMT: bone marrow transplant; CM: conditioned media; CsA: cyclosporine A; D/RCC: donor-recipient chimeric cells; HAW: hemiabdominal wall; mAbs: monoclonal antibodies; MSC: mesenchymal stem cell; RAPA: rapamycin; TBI: total body irradiation; HLOMC: hind-limb osteomyocutaneous combined flap. ∗CM from equal number of cells and concentrated 25-fold; †100-day follow-up on CsA monotherapy; ††when final surviving graft perished; §only for donor-specific ASC; §§for both cells and CM.