Mesenchymal Stromal Cells in Pediatric Hematopoietic Cell Transplantation a Review and a Pilot Study in Children Treated With Decidua Stromal Cells for Acute Graft-versus-Host Disease

Abstract

Mesenchymal stromal cells (MSCs) are rare precursors in all organs of the body. MSCs have profound anti-inflammatory effects and reduce alloreactivity in vitro and in vivo. In pediatric allogeneic hematopoietic cell transplantation (HCT), MSCs have mainly been used to treat acute graft-versus-host disease (GVHD). MSCs are commercially available for this indication in Canada, Japan, and New Zeeland. More rare indications for MSCs in pediatric patients include graft failure and chronic GVHD. MSCs from bone marrow, adipose tissue, umbilical cord, Wharton's jelly, placenta tissue, and decidua have been used, but the optimal clinical stromal cell source has not been compared in clinical trials. More experimental clinical indications using MSCs, such as sepsis, acute respiratory distress syndrome, hemorrhages, pneumo-mediastinum, and neuroinflammation have primarily been explored in animal models or adult HCT patients. MSCs have almost no if any side-effects. In this pilot study we report the outcome of six children treated with decidua stromal cells (DSCs) for steroid refractory acute GVHD. At 6 months, complete response was seen in four patients and partial response in two patients. One child with high-risk ALL died from relapse and a boy with sickle cell disease died from a cerebral hemorrhage. Five-year survival was 67% and all survivors showed a Lansky score of 100%. To conclude, MSCs from various organs are well-tolerated and have shown an encouraging outcome for acute GVHD in pediatric patients.

Mesenchymal Stromal Cells for Enhancing Hematopoietic Engraftment and Treatment of Graft-Versus-Host Disease, Hemorrhages and Acute Respiratory Distress Syndrome

“…DSCs were used to treat six pediatric patients with severe acute GvHD, grade III-IV and all six responded (118). Unfortunately, one of the patients, a teenage boy with Sickle Cell Disease (SS) died of severe brain hemorrhages a few months post HCT, but at time of HCT, he had severe sequelae due to untreated SS.…”

“…Overall, these data indicate partial effectiveness of MSCs and DSCs particularly in the treatment of severe acute GvHD in children with room for improvement. Our experience regarding DSCs in the pediatric population is limited, and further studies are needed (118). The outcome with DSCs in adults with acute GvHD is most promising (34,46,119).…”

Effects of immune system cells in GvHD and corresponding therapeutic strategies

“…GvHD in the treatment of six children with decidual stromal cells (DSCs). Further, MSCs derived from different tissues are well-tolerated and have shown promising outcomes for acute GvHD in patients [61].…”

“…Some recent studies have used MSC-EVs, because of their additional benefits, for cellular therapy in allo-HSC grafts, engraftment, and inhibition of GvHD. Application of MSC-EVs improved the effects of HSCs, including enhancing selfrenewal, inhibiting differentiation, promoting homing for HSC expansion, and preventing GvHD following HSCT [69].…”

A Promising Insight: The Potential Influence and Therapeutic Value of the Gut Microbiota in GI GVHD

“…In a pilot study, six children were treated with decidua stromal cells (DSCs) for steroid refractory aGVHD. A complete response was observed in four children, and a partial response was observed in two children at 6 months [ 122 ]. A meta-analysis showed that infusion of MSCs prevents GvHD.…”