**Acknowledgement**

have been both animal and clinical studies evaluating the use of UCB cells as a potential thera‐ py for T1D. The rationale is based on experimental studies. *In vitro* cultures of HUCB can yield islet-like structures capable of insulin and C-peptide production [64]. *In vivo*, human cord blood-derived cells is also shown to be able to differentiate into islet cells when transfused into 2 day old NOD-scid mice [65]. A recent report demonstrated that cord blood-derived multipo‐ tent stem cells reversed T1D through islet β cell regeneration following immune modulation [66]. Second, UCB contains a population of immature unprimed functional regulatory T cells. Theoretically, these cells could limit inflammatory reaction and anergize effector T cells, which are believed to mediate cellular autoimmune processes. In addition, UCB stem cells may act as nurse cells to stimulate the proliferation of new islets from the remaining viable tissue [67]. Ende et al. [68, 69] reported in two separate studies that infusions of HUCB improved hyper‐ glycemia and diabetic nephropathy in obesity-induced diabetic mice. In addition, nonobese di‐ abetic (NOD) mice can be protected from developing insulitis and diabetes by HUCB dosedependently. However, the results of available clinical study is disappointing. In a recently completed phase I clinical study [70], 24 children aged 3.4-6.9 years, with new onset T1D re‐ ceived a single autologous UBC infusion within 6 months of diagnosis. After 2 years of followup, there was no evidence of reservation of β cell function, as evaluated by the area under the curve C-peptide that was 2% of baseline 2 years after UBC infusion, despite that the numbers of regulatory T cells (Tregs) and naïve Tregs were increased 6 and 9 months after. In that study, there are several possibilities as to why UCB infusion may fail to preserve β cell function. First, the stem cell number is insufficient. Second, there exist memory T cells refractory to regulation by Tregs. Finally, it cannot be excluded that the UCB cells from the T1D patients may have in‐ trinsic defects with compromised biological function. In future, autologous or allogeneic trans‐ plantation with expanded UBC Tregs either alone or in combination of immunomodulatory drugs may be worth trying. Importantly, randomized controlled studies are needed before de‐

Mesenchymal stem cells (MSCs) were originally identified by Friedenstein et al. in 1976 [71] in the bone marrow as a fibroblast-like cell population capable of generating osteogenic pre‐ cursors. MSCs from the bone marrow (BM) are a heterogeneous, stromal population of mul‐ tipotent non-hematopoietic progenitor cells capable of differentiating into multiple mesenchymal lineages including bone, fat and cartilage. In addition to bone marrow, MSCs have been found to be present in other tissues such as adipose tissue, umbilical cord blood, synovial membrane, skeletal muscle, dermis, deciduous teeth, pericytes, trabecular bone, ar‐ ticular cartilage, umbilical cord, placenta, liver and spleen. It is now known that MSCs are able to differentiate into mesodermal and non-mesodermal cell lineages, including osteo‐ cytes, adipocytes, chondrocytes, myocytes, cardiomyocytes, fibroblasts, myofibroblasts, epi‐

In addition to their pluripotency to differentiate, MSCs have high immunomodulatory ca‐ pacity. The immunomodulatory property of MSCs are associated with their inhibitory ef‐ fects on the proliferation and differentiation of both T cells and B cells, as well as dendritic

finitive conclusions can be finally reached.

574 Type 1 Diabetes

thelial cells, and neurons [72].

**3.3. Mesenchymal stem cell therapy for TID**

This work was supported by Natural Science Foundation of China (Grant number 81172854 to CQX), and NIH 1R21DK080216-01A2 to CQX
