Table 7. Cell-based strategies for immunosuppression and immunomodulation.
| Mechanism of action | Species | Application form | Dosage examples | |
|---|---|---|---|---|
| Regulatory T cells (Tregs) | ||||
| Inhibit proliferative response of Teffs and naive T cells127 More effective in combination with Rpm125 | Mouse | i.v.130 | • 2 × 106 BMSCs, 1 × 106 Tregs130 | |
| Rat | i.v.318 | • 0.5 ml (~11.7 μg) Tregs exosomes318 | ||
| Dog | i.v. as infusion135 | • 0.6–13.7 × 108/kg donor peripheral blood lymphocytes135 | ||
| Pig | i.v.319 | • Transfusion of 15 × 106 irradiated donor-specific peripheral blood leukocytes/kg, 10 mg of CTLA4lgG4/kg after reperfusion, 10–13 mg of CsA/kg per day for 12 days319 | ||
| Mesenchymal stem cells (MSCs) | ||||
| Avoid host immunoreactions by not expressing MHC-II139 Immunomodulation via secretion of various mediators143 Regulation of T- and B-cell proliferation142, 145 | Human | i.v. as infusion150 | • 1.4 × 106/kg MSCs (0.4–9 × 106)141 • 0.6 × 106/kg MSCs150 | |
| Mouse | i.v. (Fricke, 2014, unpubl. data) | • 5 × 104 MSCs (Fricke, 2014, unpubl. data) | ||
| Rat | i.a.320 | • 1 × 104 MSCs 24 h after stroke (occlusion and reperfusion)320 | ||
| Dog | i.v. as infusion321 | • 1–30 × 106 MSCs/kg per day 2–5 times per week321 | ||
| Pig | i.m. around the graft322 | • 3 × 106 MSCs322 | ||
| Sheep | i.v.323 | • 2 × 106 MSCs/kg323 | ||
Abbreviations: BMSCs, bone marrow stem cells; CL, total plasma clearance; CsA, cyclosporin A; CTLA4, cytotoxic T-lymphocyte-associated antigen 4; i.a., intra-arterial; Ig, immunoglobulin; i.m., intramuscular; i.v., intravenous; MHC, major histocompatibility complex; Rpm, rapamycin; Teff, effector T cell; Tx, transplantation; VD, volume of distribution.