Umbilical Cord Blood-derived Mesenchymal Stem Cells for the Treatment of Steroid-refractory Acute or Chronic Graft-versus-host-disease

Overview

Graft-versus-host-disease (GVHD) is a major complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT) which may cause acute life-threatening morbidity or chronic disabilities. Although corticosteroid, the primary agent to treat GVHD, may be effective for some patients, outcomes of those who are refractory to corticosteroid are dismal. Secondary agents can be used for steroid-refractory cases; however, their efficacy is variable and usually limited. The quality of life issue of chronic GVHD is especially important for pediatric survivors who have longer life expectancy than adults. Many in-vitro and in-vivo data support immunoregulatory properties of mesenchymal stem cells(MSCs)and possibilities of treating diseases caused by immune dysregulation such as GVHD. Recent data revealed that bone marrow-derived MSCs were very useful to treat steroid-refractory acute GVHD, which led to improved overall survival compared with controls. More recently, a number of reports suggest MSCs may also be useful in treating chronic GVHD as well as acute GVHD. It has been also reported that third party MSCs are also useful as well as those from autologous or HLA-matched donors. The investigator recently demonstrated that MSCs obtained from umbilical cord blood (UCB) have similar immunosuppressive properties as bone marrow-MSCs. UCB-MSCs can be obtained without doing any harm to donors that it may be more appropriate source of MSCs than bone marrow for off-the-shelf use. However, little is known about the safety and efficacy of UCB-MSCs in treating GVHD. Therefore, the investigator designed this study to evaluate the safety and efficacy of UCB-MSCs in treating pediatric patients with steroid-refractory acute or chronic GVHD.