A Pilot Study of Mesenchymal Stem Cell Therapy for Acute Liver Allograft Rejection

Abstract

Acute allograft rejection remains common after liver transplantation despite modern immunosuppressive agents. In addition, the long‐term side effects of these regimens, including opportunistic infections, are challenging. This study evaluated the safety and clinical feasibility of umbilical cord‐derived mesenchymal stem cell (UC‐MSC) therapy in liver transplant patients with acute graft rejection. Twenty‐seven liver allograft recipients with acute rejection were randomly assigned into the UC‐MSC infusion group or the control group. Thirteen patients received one infusion of UC‐MSCs (1 × 106/kg body weight); one patient received multiple UC‐MSC infusions; 13 patients were used as controls. All enrolled patients received conventional immunosuppressive agents with follow‐up for 12 weeks after UC‐MSC infusions. No side effects occurred in treated patients. Four weeks after UC‐MSC infusions, alanine aminotransferase levels had decreased markedly and remained lower throughout the 12‐week follow‐up period. Importantly, allograft histology was improved after administration of UC‐MSCs. The percentage of regulatory T cells (Tregs) and the Treg/T helper 17 (Th17) cell ratio were significantly increased 4 weeks after infusions; in contrast, the percentage of Th17 cells showed a decreasing trend. In controls, the percentages of Tregs and Th17 cells and the Treg/Th17 ratio were statistically unchanged from the baseline measurements. Transforming growth factor beta 1 and prostaglandin E2 were increased significantly after UC‐MSC infusions; by contrast, there were no significant changes in controls. Our data suggest that UC‐MSC infusion for acute graft rejection following liver transplantation is feasible and may mediate a therapeutic immunosuppressive effect. Stem Cells Translational Medicine 2017;6:2053–2061

Cell therapy with intravascular administration of mesenchymal stromal cells continues to appear safe: An updated systematic review and meta-analysis

“…Patient populations were diverse and included cardiovascular (12 trials, n = 612 patients) [21,24À27,29,37,40,42,44,49,58], neurological (10 trials, n = 242 patients) [30À32, 36,45,48,57,62,65,69], renal (three trials, n = 177 patients) [55,63,67], liver (seven trials, n = 404 patients) [35,43,47,53,54,59,66], respiratory (three trials, n = 134 patients) [18,23,68] and endocrine diseases (four trials, n = 169 patients) [22,28,39,50], hematological/oncological malignancies (five trials, n = 318 patients) [33,34,41,46,71], immune deficient or inflammatory conditions (nine trials, n = 544 patients) [20,38,51,52,60,61,64,70,72], general frailty (one trial, n = 30 patients) [56], and severe sepsis in severely neutropenic patients with hematologic malignancies (one trial, n = 30 patients) [19].…”

“…With respect to MSC preparation and administration, of the 55 included RCTs, 31 (56¢4%) examined bone marrow [19,21-27,29-34,36,39,41-43,45,47,53,55À59,61,66,68,71], 16 (29¢1%) umbilical cord [28,35,38,40,44,46,[48][49][50][51][52]54,60,63,65,72], four (7¢3%) adipose-derived MSCs [18,20,62,64], two (3¢6%) placenta-derived cells [69,70]; and in two RCT (3¢6%) the source of MSCs was unclear [37,67]. See Supplementary Table 1 [33,34,41,67].…”

Clinical Study of Mesenchymal Stem Cell Treatment for Acute Respiratory Distress Syndrome Induced by Epidemic Influenza A (H7N9) Infection: A Hint for COVID-19 Treatment

“…The other concern is that MSC not only has potential to inhibit tumor immune responses, but also can generate new blood vessels, which may promote tumor growth and metastasis [52]. Although MSC has shown great promise in the treatment of some immunological diseases (especially GVHD), the variabilities of MSC quality from different donors and tissues are widely varies, and treatment protocols, doses and injection modes are inconsistent during experimental procedures [53]. All these factors may limit the therapeutic effect of MSC in clinical application.…”

Targeted Migration of Human Adipose-Derived Stem Cells to Secondary Lymphoid Organs Enhances Their Immunomodulatory Effect and Prolongs the Survival of Allografted Vascularized Composites

“…Consistently, some studies reported that hASCs can increase Tregs population in the allogeneic rejection scenario, such as the solid organ transplantation, hematopoietic stem cell transplantation. In a study of MSCs therapy for clinical liver transplantation, the significant increase of Tregs percentage and the Tregs/Th17 ratio were observed 4 weeks after MSCs infusions . It is also accepted that adoptive transfer of ex vivo expanded Tregs efficiently inhibit CD8 + T‐cell tissue invasion and thus delay skin graft rejection, and IL25 can promote their function .…”