Immune modulation of co-transplantation mesenchymal stem cells with islet on T and dendritic cells

Abstract

Allogeneic pancreatic islet transplantation theoretically represents a cure for type 1 diabetes. However, current immune suppressive therapies are often associated with undesired side effects. Given this problem, and the shortage of human islet donors, the majority of type 1 diabetes patients cannot currently be offered an islet transplant. However, it has been found that mesenchymal stem cells (MSCs) could exert unique immunosuppressive effects both in vitro and in vivo. Herein we transplanted allogeneic 200 islets alone or in combination with MSCs (3 x 10(6) cells) under the kidney capsules of diabetic C57LB/6 mouse. We found that the ratios of T helper type 1 (Th1) to Th2 and Tc1 to Tc2 were reduced, and the numbers of naive and memory T cells were down-regulated in peripheral blood after transplantation. In addition, the maturation, endocytosis and interleukin-12 secretion of dendritic cell (DCs)-derived bone marrow cells (BMCs) from receptor mice were suppressed. Rejection reaction was alleviated by MSCs which exerted suppressive effects through T lymphocyte subsets and DCs.

Fig. 1

Non-fasting blood glucose levels of streptozotocin-induced diabetic C57LB/6 mice after receiving 200 islets and mesenchymal stem cells (MSCs) transplanted (n = 6 in each group). Nephrectomies were performed 28 days after transplantation.*P < 0·05, compared with the B group (islet alone).

Fig. 2

Pathological micrographs of transplanted islets in renal capsules [14 days after transplantation: B group (a), C group (b), D group (c); 30 days after transplantation: B group (d)]. Haematoxylin and eosin staining ×200 magnification.

Fig. 3

The cell percentage of T helper type 1 (Th1)/Th2, Tc1/Tc2 cells in recipient mice in vivo (n = 6–7 in each group). *P < 0·05, **P < 0·01, compared with the E group.

Fig. 4

The ratio change of T helper type 1 (Th1)/Th2, Tc1/Tc2 cells in recipient mice in vivo (n = 6–7 in each group). *P < 0·05, **P < 0·01, compared with the E group.

Fig. 5

Naive and memory T cells in recipient mice in vivo (n = 6–7 in each group). *P < 0·05, **P < 0·01, compared with the E group.

Fig. 6

Immunophenotypic expression of mature dencdritic cells (mDCs) from bone marrow cells (BMC) in recipient mice in vitro (n = 6–7 in each group). *P < 0·05, **P < 0·01, compared with the E group.