title: Wharton's Jelly-Derived Mesenchymal Stromal Cells as a Promising Cellular Therapeutic Strategy for the Management of Graft-versus-Host Disease.
abstract: Allogeneic hematopoietic cell transplantation (allo-HCT), a treatment option in hematologic malignancies and bone marrow failure syndromes, is frequently complicated by Graft-versus-host disease (GVHD). The primary treatment for GVHD involves immune suppression by glucocorticoids. However, patients are often refractory to the steroid therapy, and this results in a poor prognosis. Therefore alternative therapies are needed to treat GVHD. Here, we review data supporting the clinical investigation of a novel cellular therapy using Wharton's jelly (WJ)-derived mesenchymal stromal cells (MSCs) as a potentially safe and effective therapeutic strategy in the management of GVHD. Adult-derived sources of MSCs have demonstrated signals of efficacy in the management of GVHD. However, there are limitations, including: limited proliferation capacity; heterogeneity of cell sources; lengthy expansion time to clinical dose; expansion failure in vitro; and a painful, invasive, isolation procedure for the donor. Therefore, alternative MSC sources for cellular therapy are sought. The reviewed data suggests MSCs derived from WJ may be a safe and effective cellular therapy for GVHD. Laboratories investigated and defined the immune properties of WJ-MSCs for potential use in cellular therapy. These cells represent a more uniform cell population than bone marrow-derived MSCs, displaying robust immunosuppressive properties and lacking significant immunogenicity. They can be collected safely and painlessly from individuals at birth, rapidly expanded and stored cryogenically for later clinical use. Additionally, data we reviewed suggested licensing MSCs (activating MSCs by exposure to cytokines) to enhance effectiveness in treating GVHD. Therefore, WJCs should be tested as a second generation, relatively homogeneous allogeneic cell therapy for the treatment of GVHD.
authors.affiliation: Blood and Marrow Transplant Program, The University of Kansas Medical Center, 2330 Shawnee Mission Pkwy., Suite 210 Mailstop 5003, Westwood, KS 66205, USA. jmcguirk@kumc.edu.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: McGuirk
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, 1600 Denison Ave., Coles Hall 228, Manhattan, KS 66506-5802, USA. robs32@vet.k-state.edu.
authors.forename: J Robert
authors.initials: JR
authors.lastname: Smith
authors.affiliation: Blood and Marrow Transplant Program, The University of Kansas Medical Center, 2330 Shawnee Mission Pkwy., Suite 210 Mailstop 5003, Westwood, KS 66205, USA.
authors.forename: Clint L
authors.initials: CL
authors.lastname: Divine
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, 1600 Denison Ave., Coles Hall 228, Manhattan, KS 66506-5802, USA. mjzuniga@k-state.edu.
authors.forename: Micheal
authors.initials: M
authors.lastname: Zuniga
authors.affiliation: Department of Anatomy and Physiology, Kansas State University, 1600 Denison Ave., Coles Hall 228, Manhattan, KS 66506-5802, USA. weiss@vet.k-state.edu.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Weiss