Table 1.
MSC in preclinical transplant models.
| Transplant model | MSC | Outcome | Immunological mechanism | References | ||
|---|---|---|---|---|---|---|
| Origin | Timinga | Dose/Route | ||||
| Skin tx in baboons | Donor BM | Day 0 | 1–2 × 107 /kg | Significant prolongation of graft survival | (40) | |
| Liver tx in rats (LEW in BN rats) |
BM from syngeneic, donor or TP (Wistar) rats | Days 0, +1, +2, +3, +8, +12, +16 (7 doses) | 2 × 106/dose, IV | Significant prolongation of graft survival irrespective whether MSC were of syngeneic, donor or TP origin | Foxp3+ Treg generation | (41) |
| Kidney tx in mice (C57 in BALB/c) |
Donor BM | Day 1 | 1 × 106, IV | Indefinite graft survival | IDO-dependent Foxp3+ Treg generation | (38) |
| Heart tx in mice (C57 in BALB/c mice) |
Donor BM | Day +1 | 1 × 106, IV | Indefinite graft survival by MSC in combination with low-dose rapamycin | Tolerogenic DC and Foxp3+ Treg generation | (39) |
| Kidney tx in rats (F344 in LEW rats) |
TP (SD) BM | Week 11 | 0.5 × 106, IV | Prevention from chronic renal graft dysfunction and injury (IF/TA) | Anti-inflammatory effects | (42) |
| Kidney tx in mice (BALB/c in sensitizedb C57 mice) |
Syngeneic BM | Day−1 or day−7 or double pre-tx infusion (days−7 and−1) or at day +2 | 0.5 × 106, IV | Significant prolongation of graft survival when MSC were given pre-transplant, acute graft rejection when MSC were given post-transplantation | Foxp3+ Treg generation | (43) |
| Heart tx in rats (Wistar in F344 rats) |
Donor BM | Day−7, 0, +1, +2, +3 (5 doses) | 2 × 106/dose, IV | Significant prolongation of graft survival | Reduced pro-inflammatory and increased anti-inflammatory cytokine expression | (37) |
| Heart tx in mice (C57 into BALB/c mice) |
Donor adipose tissue | Day−4 | 1 × 106, IV | Significant prolongation of graft survival by MSC in combination with MMF | Conversion into Foxp3+ Tregs (by MMF) of Th17 cells induced by MSC-educated MDSC | (44) |
| Heart tx in mice (B6C3 in C57 mice) |
Syngeneic or donor BM | Days−7 and−1 | 0.5 × 106, IV (portal vein day−7, tail vein day−1) | Significant prolongation of graft survival with either syngeneic or donor-derived MSC | Foxp3+ Treg generation | (45) |
| Corneal tx in rats (Wistar in LEW rats) |
Donor BM | Days−3,−2 and−1 or days 0, 1 and 2 | 5 × 106, IV | Significant prolongation of graft survival when MSC are given post-transplant either alone or combined with CNI | Foxp3+ Treg generation | (46) |
| Corneal tx in mice (C57 in BALB/c mice) |
Human BM | Days−7 and−3 | 1 × 106, IV | Significant prolongation of graft survival | Conversion of lung monocyte/macrophage toward an immune regulatory phenotype in a TSG-6-depedendent manner | (47) |
| Corneal tx in rats (DA in sensitizedb LEW rats) |
TP (Wistar Furth) BM | Days−7 and−1 | 1 × 106, IV | 30-day rejection free in 64% MSC-treated animals compared to 0% in the control group | Induction of PGE2/TGFβ-producing and immunosuppressive CD45+CD11b+B220+ lung monocytes and Foxp3+Treg generation | (48) |
a
From day of transplant (Day 0);
b
Donor-sensitization by donor splenocyte injection prior to transplantation.
BM, bone marrow; BN, Brown Norway; CNI, calcineurin inhibitor; DA, Dark Agouti; DC, dendritic cells; IDO, indoleamine 2,3-dioxygenase; IF/TA, interstitial fibrosis/tubular atrophy; IV, intravenous; LEW, Lewis; MMF, mycophenolate mofetil; PGE2, prostaglandin E2; SD, Sprague-Dawley; TGFβ, transforming growth factor β; TP, third-party; TSG-6, tumor necrosis factor-inducible gene 6; Tx, transplant.