title: A system for treating ischemic disease using human embryonic stem cell-derived endothelial cells without direct incorporation.
abstract: Despite studies on the use of human embryonic stem cell (hESC) derivatives to treat ischemic diseases, there are technical safety issues that have yet to be resolved. Herein, we sought to develop a method for using secreted angiogenic factors from hESC-derived endothelial cell derivatives (hESC-ECs), while avoiding direct cell incorporation, to reduce tumorigenesis or unidentified side effects of injected cells in vivo. Multicellular aggregation of hESC-ECs (MA-hESC-ECs) increases survivability, and encapsulation in Matrigel (EnMA-hESC-ECs) blocks the cells' in vivo migration. To examine the therapeutic effects of EnMA-hESC-ECs, we implanted both forms of hESC-ECs in a mouse model of hindlimb ischemia. Treatment with EnMA-hESC-ECs suppressed limb loss and tissue damage with no noticeable side effects, such as tumorigenesis or teratoma formation, and the Matrigel implant could be easily removed after the procedure. Thus, MA and the encapsulation system are effective techniques for utilizing humoral factors secreted by hESC derivatives that aid in the survivability and safety. We expect these results to contribute to the thriving stem cell field by improving the bioavailability of hESC derivatives for regenerative medicine.
authors.affiliation: CHA Bio & Diostech Co., Ltd., Seoul 135-081, Republic of Korea.
authors.forename: Sung-Hwan
authors.initials: SH
authors.lastname: Moon
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Soon-Jung
authors.initials: SJ
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Jeong Tae
authors.initials: JT
authors.lastname: Do
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Chung
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism; D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000637:transplantation; D005355:Fibrosis; D006614:Hindlimb / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D006801:Humans; D020007:Implants, Experimental; D007511:Ischemia / Q000473:pathology / Q000628:therapy*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009132:Muscles / Q000187:drug effects / Q000473:pathology; D018874:Spheroids, Cellular / Q000166:cytology / Q000187:drug effects; D033581:Stem Cell Transplantation
chemical_list: D043925:Angiogenesis Inducing Agents; D017077:Culture Media, Conditioned