Table 1.
An Overview of Recent Preclinical Studies Examining the Effects of MSCs on Islet Transplantation
| Model | Source of MSCs | Experimental Group Treatment | Timing | Result | Reference |
|---|---|---|---|---|---|
| STZ-induced diabetic rats | Lewis rat bone marrow-derived MSCs | Single injection of 1200–1600 islets and 3 × 104 BMC and 1 × 107 MSCs into portal vein | 2 weeks post-STZ, after irradiation, co-transplant of MSCs, BMCs and islets, half animals received more islets at 35 days | Induced stable mixed chimerism, MSCs enabled islet allograft tolerance without GVHD, and established immune tolerance in that after second islet transplant all rats reversed diabetes permanently | Itakura et al., 2007 (36) |
| STZ-induced diabetic Lewis rats | Lewis rat bone marrow-derived MSCs | Single injections of 3 × 6 allogeneic or syngeneic MSCs with allogeneic or syngeneic islets (600 or 1200) into the omentum | Cotransplant of MSCs and islets post onset of hyperglycemia | Allogeneic islets and syngeneic MSCs with short-term immunosuppression best, enhanced long-term graft survival, sustained normoglycemia and promoted IL-10 secreting T-cell generation | Solari et al., 2009 (67) |
| STZ-induced diabetic Lewis rats | Lewis rat bone marrow-derived MSCs | Single injection of 106 MSCs and 2000 islets into the kidney capsule | Cotransplant of MSCs and islets post onset of hyperglycemia | Animals receiving 2000 islets + MSCs maintained normoglycemia, showed increased vascularization and insulin levels | Figliuzzi et al., 2009 (23) |
| Diabetic BALB/c Rag−/− γ−/− mice reconstituted with CD4+CD25− BALB/c T cells | BALB/c mouse bone marrow-derived MSCs | Single injection of 1 × 105 syngeneic MSCs and 500 islets into the kidney capsule | Cotransplant of MSCs and islets post-onset of hyperglycemia | MSCs prolonged survival of allogeneic islet grafts in a process mediated at least in part by MMP-2 and MMP-9 | Ding et al., 2009 (17) |
| STZ-induced diabetic Lewis rats/NOD/scid mice | Lewis rat bone marrow-derived MSCs | Islets (500 or 600) and 107 MSCs into rat portal vein | Cotransplant of MSCs and islets post-onset of hyperglycemia | Reversal of diabetes with MSC s and islets, MSCs promoted vascularization | Ito et al., 2010 (37) |
| STZ-induced diabetic Sprague-Dawley and Wistar rats | Rat bone marrow-derived MSCs | Islets (700 or 1400) and single or multiple doses of syngeneic or allogeneic MSCs +/− immunosuppression into portal or tail vein | Islets 5 days post-STZ, MSCs at 0, 2, and 4 days post-transplant | Triple dose was most effective regardless of syngeneic or allogeneic MSCs, MSCs were comparable to immunosuppression but MSCs + immunosuppression were not more effective | Longoni et al., 2010 (47) |
| STZ-induced diabetic C57BL/6 mice | C57BL/6 bone marrow-derived MSCs | Allogeneic islets and 3 × 106 MSCs cotransplanted into the kidney capsule, and 1 × 106 MSCs via tail vein | MSCs delivered via tail vein injection at days 3, 2, and 0 preislet transplant and coinjected with islets | MSC treatment suppressed T-cell proliferation, promoted a shift to a T helper type 2 response, and inhibited maturation and function of dendritic cells | Li et al., 2010 (46) |
| STZ-induced diabetic cynomolgus monkeys | Cynomolgus monkey bone-marrow derived MSCs | Islets (3,000–14,000 IEQ/kg) and single or multiple doses allogeneic MSCs (1 to 6.5 × 106/kg) codelivered intraportally or via tail vein posttransplant | Islets and MSCs injection intraportally 4 weeks post STZ/IV MSCs used to treat rejection | MSC treatment enhanced islet engraftment and function at 1 month posttransplant and additional infusions of MSCs resulted in reversal of rejection episodes in 2 animals | Berman et al., 2010 (5) |
MSCs, mesenchymal stromal cells; STZ, streptozotocin; BMC, bone marrow cells; GVHD, graft versus host disease; IL-10, interleukin-10; MMP, matrix metalloproteinases; IEQ, islet equivalents; NOD/scid, nonobese diabetic/severe combined immunodeficient.